High intensity interval training improves liver and adipose tissue insulin sensitivity

PubMed Central

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

The Role of Physical Exercise to Improve the Browning of White Adipose Tissue via POMC Neurons.

PubMed

Rodrigues, Kellen C da Cruz; Pereira, Rodrigo M; de Campos, Thaís D P; de Moura, Rodrigo F; da Silva, Adelino S R; Cintra, Dennys E; Ropelle, Eduardo R; Pauli, José R; de Araújo, Michel B; de Moura, Leandro P

2018-01-01

Obesity is a public health issue that affects more than 600 million adults worldwide. The disease is characterized by fat accumulation, mainly in the abdominal area. The human body is mainly composed of two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning process generates a different type of brown fat-like adipocyte in WAT, which similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic arcuate nucleus plays an important role in WAT browning via POMC neurons, which are influenced by synergistic insulin and leptin signaling. On the other hand, stimulation of AgRP neurons suppresses WAT browning. The hypothalamic inflammatory process that occurs in obesity impairs insulin and leptin signaling in this tissue and, consequently, can decrease WAT browning. In addition, practicing physical exercise may be a great strategy for triggering the browning process since it reduces hypothalamic inflammation and increases POMC neurons gene expression. Moreover, physical exercise stimulates irisin gene expression, which has an important impact on thermogenesis, which in turn culminates in increased gene expression of proteins such as UCP-1 and Cidea, which are related to WAT browning. Furthermore, thermogenetic activation of WAT leads to increased energy expenditure, favoring obesity treatment. Therefore, this mini-review aimed to highlight the most recent studies that link the control of hypothalamic activity with the browning metabolism of adipose tissue in response to physical exercise.

Exercise (and Estrogen) Make Fat Cells “Fit”

PubMed Central

Vieira-Potter, Victoria J.; Zidon, Terese M.; Padilla, Jaume

2016-01-01

Adipose tissue inflammation links obesity and metabolic disease. Both exercise and estrogen improve metabolic health, enhance mitochondrial function, and have anti-inflammatory effects. We hypothesize that there is an inverse relationship between mitochondrial function and inflammation in adipose tissue and that exercise acts as an estrogen “mimetic”. Explicitly, exercise may improve adipose tissue “immunometabolism” by improving mitochondrial function and reducing inflammation. Summary Exercise improves adipose tissue metabolic health by reducing inflammation and improving mitochondrial function. PMID:25906425

Exercise induced adipokine changes and the metabolic syndrome.

PubMed

Golbidi, Saeid; Laher, Ismail

2014-01-01

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise

PubMed Central

Cherian, Preethi; Al-Khairi, Irina; Madhu, Dhanya; Tiss, Ali; Warsam, Samia; Alhubail, Asma; Sriraman, Devarajan; Al-Refaei, Faisal; Abubaker, Jehad

2017-01-01

Objective ANGPTL7 is a member of the Angiopoietin-like (ANGPTL) protein family that is composed of eight proteins (1–8). Increasing evidence is associating ANGPTL proteins to obesity and insulin resistance. The biological role of ANGPTL7 is yet to be understood except for a recently proposed role in the pathophysiology of glaucoma. This study was designed to shed light on the function of ANGPTL7 in obesity and its modulation by physical exercise as well as its potential association with lipid profile. Methods A total of 144 subjects were enrolled in this study and finished three months of physical exercise. The participants were classified based on their BMI, 82 subjects were non-obese and 62 obese. ANGPTL7 levels in plasma and adipose tissue were measured by ELISA, RT-PCR and immunohistochemistry. Results In this study, we showed that ANGPTL7 level was increased in the plasma of obese subjects (1249.05± 130.39 pg/mL) as compared to non-obese (930.34 ± 87.27 pg/mL) (p-Value = 0.032). ANGPTL7 Gene and protein expression levels in adipose tissue also showed over two fold increase. Physical exercise reduced circulating level of ANGPTL7 in the obese subjects to 740.98± 127.18 pg/mL, (p-Value = 0.007). ANGPTL7 expression in adipose tissue was also reduced after exercise. Finally, ANGPTL7 circulating level showed significant association with TG level in the obese subjects (R2 = 0.183, p-Value = 0.03). Conclusion In conclusion, our data shows for the first time that obesity increases the level of ANGPTL7 in both plasma and adipose tissue. Increased expression of ANGPTL7 might play a minor role in the regulation of TG level in obese subjects either directly or through interaction with other ANGPTL protein members. Physical exercise reduced the level of ANGPTL7 highlighting the potential for targeting this protein as a therapeutic target for regulating dyslipidemia. PMID:28264047

Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats.

PubMed

Rajia, S; Chen, H; Morris, M J

2013-06-01

Physical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring. Sprague-Dawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CC(EX), HC(EX), HH(EX); n=10-12). Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P<0.05). These were exaggerated by postweaning HFD (HH vs HC; P<0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P<0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HC(EX) (vs HC; P<0.05) and HH(EX) (vs HH; P<0.01). Values in HC(EX) were indistinguishable from CC, however in HH(EX) these metabolic parameters remained higher than the sedentary HC and CC rats (P<0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor α and 11β-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HH(EX) (vs HH; P<0.05). While voluntary exercise almost completely reversed the metabolic effects of maternal obesity in chow fed offspring, it did not fully attenuate the increased adiposity, glucose intolerance and insulin resistance in offspring weaned onto HFD. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity.

PubMed

Schroeder, Mariana; Shbiro, Liat; Gelber, Vered; Weller, Aron

2010-04-01

Given the alarming increase in childhood, adolescent and adult obesity there is an imperative need for understanding the early factors affecting obesity and for treatments that may help prevent or at least moderate it. Exercise is frequently considered as an effective treatment for obesity however the empirical literature includes many conflicting findings. In the present study, we used the OLETF rat model of early-onset hyperphagia-induced obesity to examine the influence of early exercise on peripheral adiposity-related parameters in both males and females. Rats were provided voluntary access to running wheels from postnatal day (PND) 22 until PND45. We examined fat pad weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size and number; and leptin, adiponectin, corticosterone and creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake. Early voluntary exercise reduced intake, adiposity and leptin in the OLETF males following a sharp reduction in adipocyte size despite a significant increase in fat cell number. Exercising males from the lean LETO control strain presented stable intake, but reduced body fat, feeding efficiency and increased plasma creatinine, suggesting an increment in muscle mass. OLETF females showed reduced feeding efficiency and liver fat, and a significant increase in brown fat. Exercising LETO control females increased intake, body weight and creatinine, but no changes in body fat. Overall, OLETF rats presented higher adiponectin levels than controls in both basal and post-exercise conditions. The results suggest an effective early time frame, when OLETF males can be successfully "re-programmed" through voluntary exercise; in OLETF females the effect is much more moderate. Findings expose sex-dependent peripheral mechanisms in coping with energy challenges. Copyright 2010 Elsevier Inc. All rights reserved.

Interactive effects of age and exercise on adiposity measures of41,582 physically active women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Paul T.; Satariano William A.

2004-06-01

The objective of this report is to assess in women whether exercise affects the estimated age-related increase in adiposity, and contrariwise, whether age affects the estimated exercise-related decrease in adiposity. Cross-sectional analyses of 64,911 female runners who provided data on their body mass index (97.6 percent), waist (91.1percent), and chest circumferences (77.9 percent). Age affected the relationships between vigorous exercise and adiposity. The decline in BMI per km/wk run was linear in 18-25 year olds (-0.023+-0.002 kg/m2 perkm run) and became increasingly nonlinear (convex or upwardly concave) with age. The waist, hip and chest circumferences declined significantly with running distancemore » across all age groups, but the declines were 52-58 percent greater in older than younger women (P<10-5). The relationships between body circumferences and running distance became increasingly convexity (upward concavity) in older women. Conversely, vigorous exercise diminished the apparent increase in adiposity with age. The rise in average BMI with age was greatest in women who ran less than 8 km/week (0.065+-0.005 kg/m2 per y), intermediate of women who ran 8-16km/wk (0.025+-0.004kg/m2 per y) or 16-32 km/wk (0.022+-0.003 kg/m2 pery), and least in those who averaged over 32 km/wk (0.017+-0.001 kg/m2 pery). Before age 45, waist circumference rose 0.055+-0.026 cm in for those who ran 0-8 km/wk, showed no significant change for those who ran 8-40km./wk, and declined -0.057+-0.012 and -0.069+-0.014 cm per year in those who ran 40 -56 and over 56 km/wk. The rise in hip and chest circumferences with age were significantly greater in women who ran under eight km/wk than longer distance runners for hip (0.231+-0.018 vs0.136+-0.004 cm/year) and chest circumferences (0.137+-0.013 vs0.053+-0.003 cm/year). These cross-sectional associations suggest that in women, age and vigorous exercise interact with each other in affecting adiposity. The extent that these cross-sectional associations are causally related to vigorous exercise or are the consequence of self-selection remains to be determined.« less

Technical note: adipose tissue blood flow in miniature swine (Sus scrofa) using the 133xenon washout technique.

PubMed

Moher, H E; Carey, G B

2002-05-01

The purpose of this study was to examine the 133xenon washout technique as a viable method for measuring adipose tissue blood flow (ATBF) in swine. Using a total of 32 female Yucatan miniature swine (Sus scrofa), the partition coefficient for 133xenon in swine subcutaneous adipose tissue was determined and ATBF was measured at rest and under various physiological conditions. These conditions included feeding, anesthesia, epinephrine infusion, and acute exercise. The effects of epinephrine and acute exercise were examined in both sedentary and exercise-trained swine. The partition coefficient value for 133xenon in swine subcutaneous adipose tissue was 9.23+/-0.26 mL/g (mean +/- SD, n = 10). The average value for resting ATBF in swine was 3.98+/-2.72 mL/(100 g tissue-min) (n = 19). Feeding increased ATBF by approximately fivefold over fasting values, and isoflurane anesthesia significantly decreased ATBF compared to rest (1.64+/-1.12 vs 3.92+/-4.22 mL/[100 g x min], n = 10). A 30-min epinephrine infusion (1 microg/[kg BW x min]) significantly increased ATBF from a resting value of 3.13+/-2.61 to 10.35+/-5.31 mL/(100 g x min) (n = 12). Epinephrine infusion into exercise-trained swine increased ATBF to the same extent as when infused into sedentary swine. An acute, 20-min bout of exercise significantly increased ATBF in swine, and the sedentary swine showed a larger increase in ATBF than their exercise-trained littermates relative to rest: 7.83 vs 2.98 mL/(100 g x min). In conclusion, the 133xenon washout technique appears to be a viable method for measuring ATBF in swine; our findings are comparable to swine ATBF values reported using the microsphere method and are consistent with values reported in animal and human studies.

The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes.

PubMed

Krout, Danielle; Schaar, Anne; Sun, Yuyang; Sukumaran, Pramod; Roemmich, James N; Singh, Brij B; Claycombe-Larson, Kate J

2017-12-15

The transient receptor potential canonical channel-1 (TRPC1) is a Ca 2+ -permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of cellular energy metabolism resulting in insulin resistance thereby leading to diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1 is involved in exercise-induced insulin sensitivity. The role of TRPC1 in adiposity and obesity-associated metabolic diseases has not yet been determined. Our results show that TRPC1 functions as a major Ca 2+ entry channel in adipocytes. We have also shown that fat mass and fasting glucose concentrations were lower in TRPC1 KO mice that were fed a high-fat (HF) (45% fat) diet and exercised as compared with WT mice fed a HF diet and exercised. Adipocyte numbers were decreased in both subcutaneous and visceral adipose tissue of TRPC1 KO mice fed a HF diet and exercised. Finally, autophagy markers were decreased and apoptosis markers increased in TRPC1 KO mice fed a HF diet and exercised. Overall, these findings suggest that TRPC1 plays an important role in the regulation of adiposity via autophagy and apoptosis and that TRPC1 inhibits the positive effect of exercise on type II diabetes risk under a HF diet-induced obesity environment.

A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue

PubMed Central

Rönn, Tina; Volkov, Petr; Davegårdh, Cajsa; Dayeh, Tasnim; Hall, Elin; Olsson, Anders H.; Nilsson, Emma; Tornberg, Åsa; Dekker Nitert, Marloes; Eriksson, Karl-Fredrik; Jones, Helena A.; Groop, Leif; Ling, Charlotte

2013-01-01

Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome. Here we describe the genome-wide pattern of DNA methylation in human adipose tissue from 23 healthy men, with a previous low level of physical activity, before and after a six months exercise intervention. We also investigate the differences in adipose tissue DNA methylation between 31 individuals with or without a family history of type 2 diabetes. DNA methylation was analyzed using Infinium HumanMethylation450 BeadChip, an array containing 485,577 probes covering 99% RefSeq genes. Global DNA methylation changed and 17,975 individual CpG sites in 7,663 unique genes showed altered levels of DNA methylation after the exercise intervention (q<0.05). Differential mRNA expression was present in 1/3 of gene regions with altered DNA methylation, including RALBP1, HDAC4 and NCOR2 (q<0.05). Using a luciferase assay, we could show that increased DNA methylation in vitro of the RALBP1 promoter suppressed the transcriptional activity (p = 0.03). Moreover, 18 obesity and 21 type 2 diabetes candidate genes had CpG sites with differences in adipose tissue DNA methylation in response to exercise (q<0.05), including TCF7L2 (6 CpG sites) and KCNQ1 (10 CpG sites). A simultaneous change in mRNA expression was seen for 6 of those genes. To understand if genes that exhibit differential DNA methylation and mRNA expression in human adipose tissue in vivo affect adipocyte metabolism, we silenced Hdac4 and Ncor2 respectively in 3T3-L1 adipocytes, which resulted in increased lipogenesis both in the basal and insulin stimulated state. In conclusion, exercise induces genome-wide changes in DNA methylation in human adipose tissue, potentially affecting adipocyte metabolism. PMID:23825961

The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue

PubMed Central

Chung, Nana; Park, Jonghoon; Lim, Kiwon

2017-01-01

[Purpose] The purpose of this study was to determine whether exercise or/and cold exposure regulate mitochondria biogenesis-related gene expression in soleus and inguinal adipose tissue of mice. [Methods] Forty ICR 5-week old male mice were divided into four groups: thermoneutrality-untrained (23 ± 1 °C in room temperature, n=10), cold-water immersion (24 ± 1 °C, n=10), exercise in neutral temperature (34 ± 1 °C, n=10), and exercise in cold temperature (24 ± 1 °C, n=10). The mice performed swimming exercise (30 min to 60 min, 5 times) for 8 weeks. After 8 weeks, we confirmed mitochondrial biogenesis-related gene expression changes for peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factors 1 (NRF1), and mitochondrial transcription factor A (Tfam) in soleus muscle and inguinal adipose tissue, and the related protein expression in soleus muscle. [Results] In soleus muscle, PGC-1α expression significantly increased in response to cold exposure (p = 0.006) and exercise (p = 0.05). There was also significant interaction between exercise and cold exposure (p = 0.005). Only exercise had a significant effect on NRF1 relative expression (p=0.001). Neither cold exposure nor the interaction showed significant effects (p = 0.1222 and p = 0.875, respectively). Relative Tfam expression did not show any significant effect from exercise. In inguinal adipose tissue, relative PGC-1α expression did not significantly change in any group. NRF1 expression showed a significant change from exercise (p = 0.01) and cold exposure (p = 0.011). There was also a significant interaction between exercise and cold exposure (p = 0.000). Tfam mRNA expression showed a significant effect from exercise (p=0.000) and an interaction between exercise and cold exposure (p=0.001). Only temperature significantly affected PGC-1α protein levels (p=0.045). Neither exercise nor the interaction were significant (p = 0.397 and p = 0.292, respectively). NRF1 protein levels did not show a significant effect in any experimental treatments. Tfam protein levels showed a significant effect in the exercise group (p=0.012), but effects of neither cold exposure nor the interaction were significant (p = 0.085 and p=0.374, respectively). [Conclusion] Exercise and cold exposure promoted increased expression of mitochondrial biogenesis- related genes in soleus muscle. Only cold exposure had a significant effect on PGC-1α protein expression and only exercise had a significant effect on Tfam protein expression. In inguinal adipose tissue, there was interaction between exercise and cold exposure in expression of mitochondrial biogenesis-related genes. PMID:28715885

IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis

PubMed Central

Pierce, Joseph R.; Maples, Jill M.

2015-01-01

Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m2; n = 10) and obese (BMI: 34.7 ± 3.5 kg/m2; n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects (P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects (P = 0.02) and was correlated with SCAT lipolysis (r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese (P < 0.01), but exercise-induced SCAT lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean (P = 0.04) but suppressed lipolysis in obese (P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown. PMID:25921578

Effect of exercise dosages on adiposity indices in overweight girls.

PubMed

Kellam, Stephanie; Olvera, Norma; Leung, Patrick; Liu, Jian; Smith, Dennis

2013-01-01

The primary purpose of this study was to determine the impact of two exercise dosages on reducing adiposity in minority girls. Sixty-two overweight Hispanic and African-American girls participated in one of two intense summer interventions in Houston, TX: Intervention A (exposure to about 40 hours physical activities) or Intervention B (exposure to 60 hours of physical activities). Adiposity indices (percent body fat, waist circumference, body mass index) were taken pre- and post-intervention. Intervention B had a significantly greater decrease in adiposity indicators (p= 0.006) when compared to Intervention A. Waist circumference displayed the most significant decrease (p = 0.001). Both interventions significantly increased daily minutes of moderate-to-vigorous physical activity (p= 0.020). Intense physical activity interventions may effectively reduce abdominal fat in minority girls.

Differential effects of aging and exercise on intra-abdominal adipose arteriolar function and blood flow regulation

PubMed Central

Davis, Robert T.; Stabley, John N.; Dominguez, James M.; Ramsey, Michael W.; McCullough, Danielle J.; Lesniewski, Lisa A.; Delp, Michael D.

2013-01-01

Adipose tissue (AT), which typically comprises an increased percentage of body mass with advancing age, receives a large proportion of resting cardiac output. During exercise, an old age-associated inability to increase vascular resistance within the intra-abdominal AT may compromise the ability of the cardiovascular system to redistribute blood flow to the active musculature, contributing to the decline in exercise capacity observed in this population. We tested the hypotheses that 1) there would be an elevated perfusion of AT during exercise with old age that was associated with diminished vasoconstrictor responses of adipose-resistance arteries, and 2) chronic exercise training would mitigate the age-associated alterations in AT blood flow and vascular function. Young (6 mo; n = 40) and old (24 mo; n = 28) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise trained (YET), or old exercise trained (OET) groups, where training consisted of 10-12 wk of treadmill exercise. In vivo blood flow at rest and during exercise and in vitro α-adrenergic and myogenic vasoconstrictor responses in resistance arteries from AT were measured in all groups. In response to exercise, there was a directionally opposite change in AT blood flow in the OSed group (∼150% increase) and YSed (∼55% decrease) vs. resting values. Both α-adrenergic and myogenic vasoconstriction were diminished in OSed vs. YSed AT-resistance arteries. Exercise training resulted in a similar AT hyperemic response between age groups during exercise (YET, 9.9 ± 0.5 ml·min−1·100−1 g; OET, 8.1 ± 0.9 ml·min−1·100−1 g) and was associated with enhanced myogenic and α-adrenergic vasoconstriction of AT-resistance arteries from the OET group relative to OSed. These results indicate that there is an inability to increase vascular resistance in AT during exercise with old age, due, in part, to a diminished vasoconstriction of AT arteries. Furthermore, the results indicate that exercise training can augment vasoconstriction of AT arteries and mitigate age-related alterations in the regulation of AT blood flow during exercise. PMID:23349454

A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice

PubMed Central

Ohyama, Kana; Nogusa, Yoshihito; Suzuki, Katsuya; Shinoda, Kosaku; Kajimura, Shingo

2014-01-01

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT. PMID:25516550

Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

PubMed

Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

2016-01-15

Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Do changing levels of maternal exercise during pregnancy affect neonatal adiposity? Secondary analysis of the babies after SCOPE: evaluating the longitudinal impact using neurological and nutritional endpoints (BASELINE) birth cohort (Cork, Ireland)

PubMed Central

Norris, Tom; McCarthy, Fergus P; Khashan, Ali S; Murray, Deidre M; Kiely, Mairead; Hourihane, Jonathan O’B; Baker, Philip N; Kenny, Louise C

2017-01-01

Objective To investigate whether changing levels of exercise during pregnancy are related to altered neonatal adiposity. Design Secondary analysis of data from a prospective cohort study. Setting Cork, Ireland. Participants 1200 mother–infant pairs recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). Main outcome measures Neonatal adiposity was assessed within several days of birth using air displacement plethysmography (PEAPOD). Per cent body fat (BF%) as a continuous outcome and a pair of dichotomous variables; high or low adiposity, representing BF% >90th or <10th centile, respectively. Multivariable linear and logistic regression models were used to investigate the relationship between exercise and the respective outcomes. Results Crude analysis revealed no association between a changing level of exercise (since becoming pregnant) at 15 weeks’ gestation and any of the outcomes (BF%, low adiposity and high adiposity). At 20 weeks’ gestation, analyses revealed that relative to women who do not change their exercise level up to 20 weeks, those women who decreased their exercise level were more likely to give birth to a neonate with adiposity above the 90th centile (OR 1.62, 95% CI 1.07 to 2.46). This association was maintained after adjustment for putative confounders (OR 1.62, 95% CI 1.06 to 2.47). Conclusions We observed a possible critical period for the association between changing exercise levels and neonatal adiposity, with no association observed with exercise recall for the first 15 weeks of gestation, but an association with a decreasing level of exercise between 15 and 20 weeks. These results should be interpreted in line with the limitations of the study and further studies utilising objectively measured estimates of exercise are required in order to replicate these findings. Trial registration number NCT01498965. PMID:29196482

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

PubMed

Hjorth, M; Pourteymour, S; Görgens, S W; Langleite, T M; Lee, S; Holen, T; Gulseth, H L; Birkeland, K I; Jensen, J; Drevon, C A; Norheim, F

2016-05-01

Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma. We further examined some effects of myostatin on energy metabolism in primary human muscle cells and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Sedentary men with or without dysglycaemia underwent a 45-min acute bicycle test before and after 12 weeks of combined endurance and strength training. Blood samples and biopsies from m. vastus lateralis and adipose tissue were collected. Myostatin mRNA expression was reduced in skeletal muscle after acute as well as long-term exercise and was even further downregulated by acute exercise on top of 12-week training. Furthermore, the expression of myostatin at baseline correlated negatively with insulin sensitivity. Myostatin expression in the adipose tissue increased after 12 weeks of training and correlated positively with insulin sensitivity markers. In cultured muscle cells but not in SGBS cells, myostatin promoted an insulin-independent increase in glucose uptake. Furthermore, muscle cells incubated with myostatin had an enhanced rate of glucose oxidation and lactate production. Myostatin was differentially expressed in the muscle and adipose tissue in relation to physical activity and dysglycaemia. Recombinant myostatin increased the consumption of glucose in human skeletal muscle cells, suggesting a complex regulatory role of myostatin in skeletal muscle homeostasis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice.

PubMed

Ohyama, Kana; Nogusa, Yoshihito; Suzuki, Katsuya; Shinoda, Kosaku; Kajimura, Shingo; Bannai, Makoto

2015-02-15

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT. Copyright © 2015 the American Physiological Society.

Antidiabetic effect of Euterpe oleracea Mart. (açaí) extract and exercise training on high-fat diet and streptozotocin-induced diabetic rats: A positive interaction

PubMed Central

de Bem, Graziele Freitas; Costa, Cristiane Aguiar; Santos, Izabelle Barcellos; Cristino Cordeiro, Viviane da Silva; de Carvalho, Lenize Costa Reis Marins; de Souza, Marcelo Augusto Vieira; Soares, Ricardo de Andrade; Sousa, Pergentino José da Cunha; Ognibene, Dayane Teixeira; de Moura, Roberto Soares

2018-01-01

A growing body of evidence suggests a protective role of polyphenols and exercise training on the disorders of type 2 diabetes mellitus (T2DM). We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on diabetic complications induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks and a single dose of STZ (35 mg/kg i.p.). Control (C) and Diabetic (D) animals were subdivided into four groups each: Sedentary, Training, ASE Sedentary, and ASE Training. ASE (200 mg/kg/day) was administered by gavage and the exercise training was performed on a treadmill (30min/day; 5 days/week) for 4 weeks after the diabetes induction. In type 2 diabetic rats, the treatment with ASE reduced blood glucose, insulin resistance, leptin and IL-6 levels, lipid profile, and vascular dysfunction. ASE increased the expression of insulin signaling proteins in skeletal muscle and adipose tissue and plasma GLP-1 levels. ASE associated with exercise training potentiated the reduction of glycemia by decreasing TNF-α levels, increasing pAKT and adiponectin expressions in adipose tissue, and IR and pAMPK expressions in skeletal muscle of type 2 diabetic rats. In conclusion, ASE treatment has an antidiabetic effect in type 2 diabetic rats by activating the insulin-signaling pathway in muscle and adipose tissue, increasing GLP-1 levels, and an anti-inflammatory action. Exercise training potentiates the glucose-lowering effect of ASE by activating adiponectin-AMPK pathway and increasing IR expression. PMID:29920546

Do changing levels of maternal exercise during pregnancy affect neonatal adiposity? Secondary analysis of the babies after SCOPE: evaluating the longitudinal impact using neurological and nutritional endpoints (BASELINE) birth cohort (Cork, Ireland).

PubMed

Norris, Tom; McCarthy, Fergus P; Khashan, Ali S; Murray, Deidre M; Kiely, Mairead; Hourihane, Jonathan O'B; Baker, Philip N; Kenny, Louise C

2017-12-01

To investigate whether changing levels of exercise during pregnancy are related to altered neonatal adiposity. Secondary analysis of data from a prospective cohort study. Cork, Ireland. 1200 mother - infant pairs recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). Neonatal adiposity was assessed within several days of birth using air displacement plethysmography (PEAPOD). Per cent body fat (BF%) as a continuous outcome and a pair of dichotomous variables; high or low adiposity, representing BF% >90th or <10th centile, respectively. Multivariable linear and logistic regression models were used to investigate the relationship between exercise and the respective outcomes. Crude analysis revealed no association between a changing level of exercise (since becoming pregnant) at 15 weeks' gestation and any of the outcomes (BF%, low adiposity and high adiposity). At 20 weeks' gestation, analyses revealed that relative to women who do not change their exercise level up to 20 weeks, those women who decreased their exercise level were more likely to give birth to a neonate with adiposity above the 90th centile (OR 1.62, 95% CI 1.07 to 2.46). This association was maintained after adjustment for putative confounders (OR 1.62, 95% CI 1.06 to 2.47). We observed a possible critical period for the association between changing exercise levels and neonatal adiposity, with no association observed with exercise recall for the first 15 weeks of gestation, but an association with a decreasing level of exercise between 15 and 20 weeks. These results should be interpreted in line with the limitations of the study and further studies utilising objectively measured estimates of exercise are required in order to replicate these findings. NCT01498965. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats.

PubMed

Goularte, Jéferson F; Ferreira, Maria B C; Sanvitto, Gilberto L

2012-10-28

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise

PubMed Central

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-01-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. PMID:25875578

Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta.

PubMed

Yan, Zhen Cheng; Liu, Dao Yan; Zhang, Li Li; Shen, Chen Yi; Ma, Qun Li; Cao, Ting Bing; Wang, Li Juan; Nie, Hai; Zidek, Walter; Tepel, Martin; Zhu, Zhi Ming

2007-03-09

Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p<0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p<0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-delta. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-delta. Furthermore, selective silencing of PPAR-delta by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00+/-0.06 (n=3) to 1.91+/-0.06 (n=3; p<0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-delta significantly reduced CB1 expression to 0.39+/-0.03 (n=3; p<0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-delta. Both CB1 and PPAR-delta are intimately involved in therapeutic interventions against a most important cardiovascular risk factor.

Dairy Attenuates Weight Gain to a Similar Extent as Exercise in Rats Fed a High-Fat, High-Sugar Diet.

PubMed

Trottier, Sarah K; MacPherson, Rebecca E K; Knuth, Carly M; Townsend, Logan K; Peppler, Willem T; Mikhaeil, John S; Leveille, Cam F; LeBlanc, Paul J; Shearer, Jane; Reimer, Raylene A; Wright, David C

2017-10-01

To compare the individual and combined effects of dairy and endurance exercise training in reducing weight gain and adiposity in a rodent model of diet-induced obesity. An 8-week feeding intervention of a high-fat, high-sugar diet was used to induce obesity in male Sprague-Dawley rats. Rats were then assigned to one of four groups for 6 weeks: (1) casein sedentary (casein-S), (2) casein exercise (casein-E), (3) dairy sedentary (dairy-S), and (4) dairy exercise (dairy-E). Rats were exercise trained by treadmill running 5 d/wk. Dairy-E prevented weight gain to a greater extent than either dairy or exercise alone. Adipose tissue and liver mass were reduced to a similar extent in dairy-S, casein-E, and dairy-E groups. Differences in weight gain were not explained by food intake or total energy expenditure. The total amount of lipid excreted was greater in the dairy-S compared to casein-S and dairy-E groups. This study provides evidence that dairy limits weight gain to a similar extent as exercise training and the combined effects are greater than either intervention alone. While exercise training reduces weight gain through increases in energy expenditure, dairy appears to increase lipid excretion in the feces. © 2017 The Obesity Society.

Visceral and subcutaneous adipose tissue express and secrete functional alpha2hsglycoprotein (fetuin a) especially in obesity.

PubMed

Pérez-Sotelo, Diego; Roca-Rivada, Arturo; Larrosa-García, María; Castelao, Cecilia; Baamonde, Iván; Baltar, Javier; Crujeiras, Ana Belen; Seoane, Luisa María; Casanueva, Felipe F; Pardo, María

2017-02-01

The secretion of the hepatokine alpha-2-Heremans-Schmid glycoprotein/Fetuin A, implicated in pathological processes including systemic insulin resistance, by adipose tissue has been recently described. Thus, we have recently identified its presence in white adipose tissue secretomes by mass spectrometry. However, the secretion pattern and function of adipose-derived alpha-2-Heremans-Schmid glycoprotein are poorly understood. The aim of this study is to evaluate the expression and secretion of total and active phosphorylated alpha-2-Heremans-Schmid glycoprotein by adipose tissue from visceral and subcutaneous localizations in animals at different physiological and nutritional status including anorexia and obesity. Alpha-2-Heremans-Schmid glycoprotein expression and secretion in visceral adipose tissue and subcutaneous adipose tissue explants from animals under fasting and exercise training, at pathological situations such as anorexia and obesity, and from human obese individuals were assayed by immunoblotting, quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. We reveal that visceral adipose tissue expresses and secretes more alpha-2-Heremans-Schmid glycoprotein than subcutaneous adipose tissue, and that this secretion is diminished after fasting and exercise training. Visceral adipose tissue from anorectic animals showed reduced alpha-2-Heremans-Schmid glycoprotein secretion; on the contrary, alpha-2-Heremans-Schmid glycoprotein is over-secreted by visceral adipose tissue in the occurrence of obesity. While secretion of active-PhophoSer321α2HSG by visceral adipose tissue is independent of body mass index, we found that the fraction of active-alpha-2-Heremans-Schmid glycoprotein secreted by subcutaneous adipose tissue increments significantly in situations of obesity. Functional studies show that the inhibition of adipose-derived alpha-2-Heremans-Schmid glycoprotein increases insulin sensitivity in differentiated adipocytes. In conclusion, visceral adipose tissue secretes more alpha-2-Heremans-Schmid glycoprotein than subcutaneous adipose tissue and this secretion is more sensitive to nutritional and physiological changes. The over-secretion of alpha-2-Heremans-Schmid glycoprotein by visceral adipose tissue, the increased secretion of the active phosphorylated form by subcutaneous adipose tissuein obese animals, and the adipose-derived alpha-2-Heremans-Schmid glycoprotein capacity to inhibit the insulin pathway suggest the participation of adipose-derived alpha-2-Heremans-Schmid glycoprotein in the deleterious effects of obesity.

Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis.

PubMed

Rao, Rajesh R; Long, Jonathan Z; White, James P; Svensson, Katrin J; Lou, Jesse; Lokurkar, Isha; Jedrychowski, Mark P; Ruas, Jorge L; Wrann, Christiane D; Lo, James C; Camera, Donny M; Lachey, Jenn; Gygi, Steven; Seehra, Jasbir; Hawley, John A; Spiegelman, Bruce M

2014-06-05

Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines. Metrnl stimulates an eosinophil-dependent increase in IL-4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat. Importantly, blocking Metrnl actions in vivo significantly attenuates chronic cold-exposure-induced alternative macrophage activation and thermogenic gene responses. Thus, Metrnl links host-adaptive responses to the regulation of energy homeostasis and tissue inflammation and has therapeutic potential for metabolic and inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat.

PubMed

Company, Joseph M; Booth, Frank W; Laughlin, M Harold; Arce-Esquivel, Arturo A; Sacks, Harold S; Bahouth, Suleiman W; Fain, John N

2010-12-01

Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies.

Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat

PubMed Central

Booth, Frank W.; Laughlin, M. Harold; Arce-Esquivel, Arturo A.; Sacks, Harold S.; Bahouth, Suleiman W.; Fain, John N.

2010-01-01

Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies. PMID:20947714

Short-term regular aerobic exercise reduces oxidative stress produced by acute in the adipose microvasculature.

PubMed

Robinson, Austin T; Fancher, Ibra S; Sudhahar, Varadarajan; Bian, Jing Tan; Cook, Marc D; Mahmoud, Abeer M; Ali, Mohamed M; Ushio-Fukai, Masuko; Brown, Michael D; Fukai, Tohru; Phillips, Shane A

2017-05-01

High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm 2 ) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to H 2 O 2 Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature. NEW & NOTEWORTHY We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression.

Improving Metabolic Health in Obese Male Mice via Diet and Exercise Restores Embryo Development and Fetal Growth

PubMed Central

McPherson, Nicole O.; Bakos, Hassan W.; Owens, Julie A.; Setchell, Brian P.; Lane, Michelle

2013-01-01

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health. PMID:23977045

High-intensity interval training and calorie restriction promote remodeling of glucose and lipid metabolism in diet-induced obesity.

PubMed

Davis, Rachel A H; Halbrooks, Jacob E; Watkins, Emily E; Fisher, Gordon; Hunter, Gary R; Nagy, Tim R; Plaisance, Eric P

2017-08-01

Calorie restriction (CR) decreases adiposity, but the magnitude and defense of weight loss is less than predicted due to reductions in total daily energy expenditure (TEE). The purpose of the current investigation was to determine whether high-intensity interval training (HIIT) would increase markers of sympathetic activation in white adipose tissue (WAT) and rescue CR-mediated reductions in EE to a greater extent than moderate-intensity aerobic exercise training (MIT). Thirty-two 5-wk-old male C57BL/6J mice were placed on ad libitum HFD for 11 wk, followed by randomization to one of four groups ( n = 8/group) for an additional 15 wk: 1 ) CON (remain on HFD), 2 ) CR (25% lower energy intake), 3 ) CR + HIIT (25% energy deficit created by 12.5% CR and 12.5% EE through HIIT), and 4 ) CR + MIT (25% energy deficit created by 12.5% CR and 12.5% EE through MIT). Markers of adipose thermogenesis ( Ucp1 , Prdm16 , Dio2 , and Fgf21 ) were unchanged in either exercise group in inguinal or epididymal WAT, whereas CR + HIIT decreased Ucp1 expression in retroperitoneal WAT and brown adipose tissue. HIIT rescued CR-mediated reductions in lean body mass (LBM) and resting energy expenditure (REE), and both were associated with improvements in glucose/insulin tolerance. Improvements in glucose metabolism in the CR + HIIT group appear to be linked to a molecular signature that enhances glucose and lipid storage in skeletal muscle. Exercise performed at either moderate or high intensity does not increase markers of adipose thermogenesis when performed in the presence of CR but remodels skeletal muscle metabolic and thermogenic capacity. Copyright © 2017 the American Physiological Society.

The prospective association between different types of exercise and body composition

PubMed Central

Drenowatz, Clemens; Hand, Gregory A.; Sagner, Michael; Shook, Robin P.; Burgess, Stephanie; Blair, Steven N.

2015-01-01

Purpose Despite the widely accepted benefits of exercise on chronic disease risk, there remains controversy on the role of exercise in weight loss. This study examined the effect of different exercise types on measures of adiposity across different fat categories. Methods A total of 348 young adults (49% male; 28±4 years), participating in an ongoing observational study, provided valid data over a period of 12 months. Fat mass (FM) and lean mass (LM) were measured via dual x-ray absorptiometry every 3 months. Percent body fat (BF) was calculated and used to differentiate between normal fat, over fat and obese participants. At each measurement time point participants reported engagement (min/week) in aerobic exercise, resistance exercise and other exercise. Results Most participants (93%) reported some exercise participation during the observation period. Total exercise or specific exercise types did not significantly affect subsequent BMI after adjusting for sex, ethnicity, age and baseline values of adiposity and exercise. Resistance exercise affected lean mass (p<0.01) and fat mass (p<0.01), while aerobic exercise only affected fat mass (p<0.01). Any exercise type positively affected lean mass in normal fat participants (p<0.04). In overfat and obese participants fat mass was reduced with increasing resistance exercise (p≤0.02) but not with aerobic exercise (p≥0.09). Additionally adjusting for objectively assessed total physical activity level did not change these results. Conclusion Despite the limited effects on BMI, exercise was associated with beneficial changes in body composition. Exercise increased lean mass in normal fat participants and reduced fat mass in overfat and obese adults. Adults with excess body fat may benefit particularly from resistance exercise. PMID:25970664

The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise.

PubMed

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-06-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. © 2015 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

Prior exercise training blunts short-term high-fat diet-induced weight gain.

PubMed

Snook, Laelie A; MacPherson, Rebecca E K; Monaco, Cynthia M F; Frendo-Cumbo, Scott; Castellani, Laura; Peppler, Willem T; Anderson, Zachary G; Buzelle, Samyra L; LeBlanc, Paul J; Holloway, Graham P; Wright, David C

2016-08-01

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet. Copyright © 2016 the American Physiological Society.

Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats.

PubMed

Estadella, Debora; Oyama, Lila M; Dâmaso, Ana R; Ribeiro, Eliane B; Oller Do Nascimento, Claudia M

2004-02-01

The present study was designed to examine 1) whether continuous feeding with a palatable hyperlipidic diet and cycling this diet with chow diet would affect lipid and carbohydrate metabolism in a similar way; and 2) whether the effect of chronic exercise on lipid and carbohydrate metabolism would be modified by these diet regimens. Male 25-d-old Wistar rats were assigned to one of six groups: sedentary rats fed with chow diet; exercised (swimming 90 min/d, 5 d/wk) rats fed with chow diet; sedentary rats fed with a palatable hyperlipidic diet; exercised rats fed with the palatable hyperlipidic diet; sedentary rats fed with food cycles (four cycles alternating the chow and hyperlipidic diets weekly); and exercised rats fed with food cycles. After 8 wk of treatment, the animals were killed 24 h after the last exercise session. The hyperlipidic diet and food cycles schedules caused similar increases in body weight gain, carcass lipogenesis rate and adiposity, lipid content of the liver and gastrocnemius muscle, and serum total lipid, triacylglycerol, insulin, and leptin levels. The exercise attenuated body weight gain, adipose tissue mass, and serum triacylglycerol, insulin, and leptin levels similarly in the hyperlipidic and food cycles groups. Carcass lipogenesis rate was not affected by exercise in any of the three groups. The data showed that the continuous intake of a hyperlipidic palatable diet for 8 wk and the alternation of the high-fat intake with periods of chow intake cause obesity and affected lipid metabolism in a similar way. Chronic exercise attenuated body weight gain and adiposity and improved serum lipid concentrations in both high-fat feeding regimens.

Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise.

PubMed

Uddin, Golam Mezbah; Youngson, Neil A; Doyle, Bronte M; Sinclair, David A; Morris, Margaret J

2017-11-08

Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD + ). We have shown that the NAD + precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers. Five week old lean and obese female C57BL6/J mice were mated with chow fed males. Female offspring weaned onto HFD were given treadmill exercise for 9 weeks, or NMN injection daily for 18 days. Maternal obesity programmed increased adiposity and liver triglycerides, with decreased glucose tolerance, liver NAD + levels and citrate synthase activity in offspring. Both interventions reduced adiposity, and showed a modest improvement in glucose tolerance and improved markers of mitochondrial function. NMN appeared to have stronger effects on liver fat catabolism (Hadh) and synthesis (Fasn) than exercise. The interventions appeared to exert the most global benefit in mice that were most metabolically challenged (HFD-consuming offspring of obese mothers). This work encourages further study to confirm the suitability of NMN for use in reversing metabolic dysfunction linked to programming by maternal obesity.

The impact of exercise intensity on whole body and adipose tissue metabolism during energy restriction in sedentary overweight men and postmenopausal women.

PubMed

Walhin, Jean-Philippe; Dixon, Natalie C; Betts, James A; Thompson, Dylan

2016-12-01

This study aimed to establish whether vigorous-intensity exercise offers additional adipose-related health benefits and metabolic improvements compared to energy-matched moderate-intensity exercise. Thirty-eight sedentary overweight men (n = 24) and postmenopausal women (n = 14) aged 52 ± 5 years (mean ± standard deviations [SD]) were prescribed a 3-week energy deficit (29302 kJ∙week -1 ) achieved by increased isocaloric moderate or vigorous-intensity exercise (+8372 kJ∙week -1 ) and simultaneous restricted energy intake (-20930 kJ∙week -1 ). Participants were randomly assigned to either an energy-matched vigorous (VIG; n = 18) or moderate (MOD; n = 20) intensity exercise group (five times per week at 70% or 50% maximal oxygen uptake, respectively). At baseline and follow-up, fasted blood samples and abdominal subcutaneous adipose tissue biopsies were obtained and oral glucose tolerance tests conducted. Body mass was reduced similarly in both groups (∆ 2.4 ± 1.1 kg and ∆ 2.4 ± 1.4 kg, respectively, P < 0.05). Insulinemic responses to a standard glucose load decreased similarly at follow-up relative to baseline in VIG (∆ 8.6 ± 15.4 nmol.120 min.l -1 ) and MOD (∆ 5.4 ± 8.5 nmol.120 min.l -1 ; P < 0.05). Expression of SREBP-1c and FAS in adipose tissue was significantly down-regulated, whereas expression of PDK4 and hormone-sensitive lipase (HSL) was significantly up-regulated in both groups (P < 0.05). Thus, when energy expenditure and energy deficit are matched, vigorous or moderate-intensity exercise combined with energy restriction provide broadly similar (positive) changes in metabolic control and adipose tissue gene expression. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise

PubMed Central

2011-01-01

Background Alterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1) and fatty acid amide hydrolase (FAAH) are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women. Methods Thirty overweight or obese, middle-aged women (BMI = 34.3 ± 0.8 kg/m2, age = 59 ± 1 years) underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N = 9), caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N = 13), or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N = 8). Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression. Results At baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08 ± 0.11 vs. 1.78 ± 0.10, expressed as target gene/β-actin mRNA ratio × 10-3, P < 0.05). Compared to pre-intervention, CR did not change abdominal, but decreased gluteal CB1 (Δ = -0.82 ± 0.25, P < 0.05) and FAAH (Δ = -0.49 ± 0.14, P < 0.05) gene expression. CRM or CRV alone did not change adipose tissue CB1 and FAAH gene expression. However, combined CRM and CRV (CRM+CRV) decreased abdominal adipose tissue FAAH gene expression (Δ = -0.37 ± 0.18, P < 0.05). The changes in gluteal CB1 and abdominal FAAH gene expression levels in the CR alone and the CRM+CRV group were different (P < 0.05) or tended to be different (P = 0.10). Conclusions There are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss. Trial Registration ClinicalTrials.gov: NCT00664729. PMID:22035053

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

PubMed

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Lifestyle interventions targeting body weight changes during the menopause transition: a systematic review.

PubMed

Jull, Janet; Stacey, Dawn; Beach, Sarah; Dumas, Alex; Strychar, Irene; Ufholz, Lee-Anne; Prince, Stephanie; Abdulnour, Joseph; Prud'homme, Denis

2014-01-01

To determine the effectiveness of exercise and/or nutrition interventions and to address body weight changes during the menopause transition. A systematic review of the literature was conducted using electronic databases, grey literature, and hand searching. Two independent researchers screened for studies using experimental designs to evaluate the impact of exercise and/or nutrition interventions on body weight and/or central weight gain performed during the menopausal transition. Studies were quality appraised using Cochrane risk of bias. Included studies were analyzed descriptively. Of 3,564 unique citations screened, 3 studies were eligible (2 randomized controlled trials, and 1 pre/post study). Study quality ranged from low to high risk of bias. One randomized controlled trial with lower risk of bias concluded that participation in an exercise program combined with dietary interventions might mitigate body adiposity increases, which is normally observed during the menopause transition. The other two studies with higher risk of bias suggested that exercise might attenuate weight loss or weight gain and change abdominal adiposity patterns. High quality studies evaluating the effectiveness of interventions targeting body weight changes in women during their menopause transition are needed. Evidence from one higher quality study indicates an effective multifaceted intervention for women to minimize changes in body adiposity.

Lifestyle Interventions Targeting Body Weight Changes during the Menopause Transition: A Systematic Review

PubMed Central

Jull, Janet; Stacey, Dawn; Beach, Sarah; Dumas, Alex; Strychar, Irene; Ufholz, Lee-Anne; Prince, Stephanie; Abdulnour, Joseph; Prud'homme, Denis

2014-01-01

Objective. To determine the effectiveness of exercise and/or nutrition interventions and to address body weight changes during the menopause transition. Methods. A systematic review of the literature was conducted using electronic databases, grey literature, and hand searching. Two independent researchers screened for studies using experimental designs to evaluate the impact of exercise and/or nutrition interventions on body weight and/or central weight gain performed during the menopausal transition. Studies were quality appraised using Cochrane risk of bias. Included studies were analyzed descriptively. Results. Of 3,564 unique citations screened, 3 studies were eligible (2 randomized controlled trials, and 1 pre/post study). Study quality ranged from low to high risk of bias. One randomized controlled trial with lower risk of bias concluded that participation in an exercise program combined with dietary interventions might mitigate body adiposity increases, which is normally observed during the menopause transition. The other two studies with higher risk of bias suggested that exercise might attenuate weight loss or weight gain and change abdominal adiposity patterns. Conclusions. High quality studies evaluating the effectiveness of interventions targeting body weight changes in women during their menopause transition are needed. Evidence from one higher quality study indicates an effective multifaceted intervention for women to minimize changes in body adiposity. PMID:24971172

Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats.

PubMed

Santos, Mery; Rodríguez-González, Guadalupe L; Ibáñez, Carlos; Vega, Claudia C; Nathanielsz, Peter W; Zambrano, Elena

2015-02-01

Exercise improves health but few data are available regarding benefits of exercise in offspring exposed to developmental programming. There is currently a worldwide epidemic of obesity. Obesity in pregnant women predisposes offspring to obesity. Maternal obesity has well documented effects on offspring reproduction. Few studies address ability of offspring exercise to reduce adverse outcomes. We observed increased oxidative stress and impaired sperm function in rat offspring of obese mothers. We hypothesized that regular offspring exercise reverses adverse effects of maternal obesity on offspring sperm quality and fertility. Female Wistar rats ate chow (C) or high-energy, obesogenic diet (MO) from weaning through lactation, bred at postnatal day (PND) 120, and ate their pregnancy diet until weaning. All offspring ate C diet from weaning. Five male offspring (different litters) ran on a wheel for 15 min, 5 times/week from PND 330 to 450 and were euthanized at PND 450. Average distance run per session was lower in MO offspring who had higher body weight, adiposity index, and gonadal fat and showed increases in testicular oxidative stress biomarkers. Sperm from MO offspring had reduced antioxidant enzyme activity, lower sperm quality, and fertility. Exercise in MO offspring decreased testicular oxidative stress, increased sperm antioxidant activity and sperm quality, and improved fertility. Exercise intervention has beneficial effects on adiposity index, gonadal fat, oxidative stress markers, sperm quality, and fertility. Thus regular physical exercise in male MO offspring recuperates key male reproductive functions even at advanced age: it's never too late. Copyright © 2015 the American Physiological Society.

Cross-sectional relationships of exercise and age to adiposity in60,617 male runners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Paul T.; Pate, Russell R.

2004-06-01

The objective of this report is to assess in men whether exercise affects the estimated age-related increase in adiposity, and contrariwise, whether age affects the estimated exercise-related decrease in adiposity. Cross-sectional analyses of 64,911 male runners who provided data on their body mass index (97.6 percent), waist (91.1 percent), hip (47.1 percent), and chest circumferences (77.9 percent). Between 18 to 55 years old, the decline in BMI with weekly distance run (slope+-SE) was significantly greater in men 25-55 years old (slope+-:-0.036+-0.001 kg/m2 per km/wk) than in younger men (-0.020+-0.002 kg/m 2 per km/wk). Declines in waist circumference with running distancemore » were also significantly greater in older than younger men (P<10-9 for trend),i.e., the slopes decreased progressively from -0.035+-0.004 cm per km/wk in 18-25 year old men to -0.097+-0.003 cm per km/wk in 50-55 year old men. Increases in BMI with age were greater for men who ran under 16km/wk than for longer distance runners. Waist circumference increased with age at all running levels, but the increase appeared to diminish by running further (0.259+-0.015 cm per year if running<8 km/wk and 0.154+-0.003 cm per year for>16 km/wk). In men over 50 years old, BMI declined -0.038+-0.001 kg/m2 per km/wk run when adjusted for age and declined -0.054+-0.003 kg/m2 (increased 0.021+-0.007 cm) per year of age when adjusted for running distance. Their waist circumference declined-0.096+-0.002 cm per km/wk run when adjusted for age and increased 0.021+-0.007 cm per year of age when adjusted for running distance. These cross-sectional data suggest that age and vigorous exercise interact with each other in affecting mens adiposity, and support the proposition that vigorous physical activity must increase with age to prevent middle-age weight gain. We estimate that a man who ran 16 km/wk at age 25 would need to increase their weekly running distance by 65.7 km/wk by age 50 in order to maintain his same waist circumference.« less

Voluntary exercise improves high-fat diet-induced leptin resistance independent of adiposity.

PubMed

Krawczewski Carhuatanta, Kimberly A; Demuro, Giovanna; Tschöp, Matthias H; Pfluger, Paul T; Benoit, Stephen C; Obici, Silvana

2011-07-01

The efficacy of exercise as primary prevention of obesity is the subject of intense investigation. Here, we show that voluntary exercise in a mouse strain susceptible to diet-induced obesity (C57B6J) decreases fat mass and increases energy expenditure. In addition, exercise attenuates obesity in mice fed a high-fat diet (HFD). Using FosB immunoreactivity as a marker of chronic neuronal activation, we found that exercise activates leptin receptor-positive neurons in the ventromedial hypothalamic nucleus, involved in homeostatic control of energy balance. FosB immunoreactivity in the ventromedial hypothalamic nucleus is decreased in sedentary mice exposed to HFD but is increased in exercised mice independent of adiposity. To determine whether the antiobesity effects of voluntary exercise improve central nervous system (CNS) leptin action, we measured the anorectic and weight reducing effects of intracerebroventricular (ICV) leptin in sedentary and exercised mice exposed to HFD (EH), as well as in sedentary mice that have been calorie restricted (SR) to match the fat mass of EH mice. ICV leptin was ineffective in lowering food intake and body weight (BW) in sedentary mice exposed to HFD mice. The anorectic potency of leptin was partially restored in EH and SR groups. However, ICV leptin significantly lowered BW in EH but not SR mice. Thus, exercise leads to the maintenance of a lower BW and leaner composition, as well as to improved CNS leptin action, independent of fat mass. These results support the notion that physical exercise directly influences the responsiveness of the CNS circuits involved in energy homeostasis by allowing the defense of a lowered BW.

Skeletal muscle IL-6 regulates muscle substrate utilization and adipose tissue metabolism during recovery from an acute bout of exercise.

PubMed

Knudsen, Jakob G; Gudiksen, Anders; Bertholdt, Lærke; Overby, Peter; Villesen, Ida; Schwartz, Camilla L; Pilegaard, Henriette

2017-01-01

An acute bout of exercise imposes a major challenge on whole-body metabolism and metabolic adjustments are needed in multiple tissues during recovery to reestablish metabolic homeostasis. It is currently unresolved how this regulation is orchestrated between tissues. This study was undertaken to clarify the role of skeletal muscle derived interleukin 6 (IL-6) in the coordination of the metabolic responses during recovery from acute exercise. Skeletal muscle specific IL-6 knockout (IL-6 MKO) and littermate Control mice were rested or ran on a treadmill for 2h. Plasma, skeletal muscle, liver and adipose tissue were obtained after 6 and 10h of recovery. Non-exercised IL-6 MKO mice had higher plasma lactate and lower plasma non-esterified fatty acids than Controls. The activity of pyruvate dehydrogenase in the active form was, in skeletal muscle, higher in IL-6 MKO mice than Controls in non-exercised mice and 6h after exercise. IL-6 MKO mice had lower glucose transporter 4 protein content in inguinal adipose tissue (WAT) than Control in non-exercised mice and 10h after treadmill running. Epididymal WAT hormone sensitive lipase phosphorylation and inguinal WAT mitogen activated kinase P38 phosphorylation were higher in IL-6 MKO than Control mice 6h after exercise. These findings indicate that skeletal muscle IL-6 may play an important role in the regulation of substrate utilization in skeletal muscle, basal and exercise-induced adaptations in adipose tissue glucose uptake and lipolysis during recovery from exercise. Together this indicates that skeletal muscle IL-6 contributes to reestablishing metabolic homeostasis during recovery from exercise by regulating WAT and skeletal muscle metabolism.

Dose dependent effects of exercise training and detraining ontotal and regional adiposity in 4,663 men and 1,743

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Paul T.; Thompson, Paul D.

2006-01-06

Objective: To determine if exercise reduces body weight andto examine the dose-response relationships between changes in exerciseand changes in total and regional adiposity. Methods and Results:Questionnaires on weekly running distance and adiposity from a largeprospective study of 3,973 men and 1,444 women who quit running(detraining), 270 men and 146 women who started running (training) and420 men and 153 women who remained sedentary during 7.4 years offollow-up. There were significant inverse relationships between change inthe amount of vigorous exercise (km/wk run) and changes in weight and BMIin men (slope+-SE:-0.039+-0.005 kg and -0.012+-0.002 kg/m2 per km/wk,respectively) and older women (-0.060+-0.018 kg andmore » -0.022+-0.007 kg/m2per km/wk) who quit running, and in initially sedentary men(-0.098+-0.017 kg and -0.032+-0.005 kg/m2 per km/wk) and women(-0.062+-0.023 kg and -0.021+-0.008 kg/m2 per km/wk) who started running.Changes in waist circumference were also inversely related to changes inrunning distance in men who quit (-0.026+-0.005 cm per km/wk) or startedrunning (-0.078+-0.017 cm per km/wk). Conclusions. The initiation andcessation of vigorous exercise decrease and increase body weight andintra-abdominal fat, respectively, and these changes are proportional tothe change in exercise dose.« less

Regulation of angiopoietin‐like protein 4 production during and after exercise

PubMed Central

Norheim, Frode; Hjorth, Marit; Langleite, Torgrim M.; Lee, Sindre; Holen, Torgeir; Bindesbøll, Christian; Stadheim, Hans K.; Gulseth, Hanne L.; Birkeland, Kåre I.; Kielland, Anders; Jensen, Jørgen; Dalen, Knut T.; Drevon, Christian A.

2014-01-01

Abstract Angiopoietin‐like protein 4 (ANGPTL4) may regulate lipoprotein lipase‐dependent plasma clearance of triacylglycerol from skeletal muscle during exercise. The aim of this study was to examine the importance of muscle in regulating ANGPTL4 in response to exercise. We sampled muscle biopsies and serum before, immediately after, and 2 h after 45 min of ergometer cycling. Sampling was done before and after a 12‐week training intervention in controls and dysglycemic subjects. Moreover, fat biopsies were taken before and after the training intervention. The regulation of ANGPTL4 was also investigated in several tissues of exercising mice, and in cultured myotubes. ANGPTL4 levels in serum and expression in muscle were highest 2 h after exercise in both groups. Whereas ANGPTL4 was higher in muscle of exercising controls as compared to dysglycemic subjects, the opposite was observed in serum. In exercising mice, Angptl4 mRNA showed both higher basal expression and induction in liver compared to muscle. Angptl4 mRNA was much higher in adipose tissue than muscle and was also induced by exercise. We observed two mRNA isoforms of ANGPTL4 in muscle and fat in humans. Both were induced by exercise in muscle; one isoform was expressed 5‐ to 10‐fold higher than the other. Studies in mice and cultured myotubes showed that both fatty acids and cortisol have the potential to increase ANGPTL4 expression in muscle during exercise. In conclusion, ANGPTL4 is markedly induced in muscle in response to exercise. However, liver and adipose tissue may contribute more than muscle to the exercise‐induced increase in circulating ANGPTL4. PMID:25138789

Regional Differences in Adipose Tissue Hormone/Cytokine Production Before and After Weight Loss in Abdominally Obese Women

PubMed Central

You, Tongjian; Wang, Xuewen; Murphy, Karin M.; Lyles, Mary F.; Demons, Jamehl L.; Yang, Rongze; Gong, Da-Wei; Nicklas, Barbara J.

2014-01-01

Objective To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. Design and Methods Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ~2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Results Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. The intervention resulted in significant weight loss (−10.1 ±0.7 kg, P<0.001). At baseline, gene expression of adiponectin were higher (P<0.01), and gene expression and release of IL-6 were lower (both P<0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P<0.05 to P<0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P<0.05). Conclusion A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity. PMID:24634403

Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

PubMed

Tamura, Shohei; Honda, Kazuhisa; Morinaga, Ryoji; Saneyasu, Takaoki; Kamisoyama, Hiroshi

2017-01-01

The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

Exercise prevents high fat diet-induced bone loss, marrow adiposity and dysbiosis in male mice.

PubMed

McCabe, Laura R; Irwin, Regina; Tekalur, Arjun; Evans, Christian; Schepper, Jonathan D; Parameswaran, Narayanan; Ciancio, Mae

2018-03-29

High fat diets can have detrimental effects on the skeleton as well as cause intestinal dysbiosis. Exercise prevents high fat (HF) diet-induced obesity and also improves bone density and prevents the intestinal dysbiosis that promotes energy storage. Previous studies indicate a link between intestinal microbial balance and bone health. Therefore, we examined whether exercise could prevent HF-induced bone pathology in male mice and determined whether benefits correlate to changes in host intestinal microbiota. Male C57Bl/6 mice were fed either a low fat diet (LF; 10 kcal% fat) or a HF diet (60 kcal% fat) and put under sedentary or voluntary exercise conditions for 14 weeks. Our results indicated that HF diet reduced trabecular bone volume, when corrected for differences in body weight, of both the tibia (40% reduction) and vertebrae (25% reduction) as well and increased marrow adiposity (44% increase). More importantly, these effects were prevented by exercise. Exercise also had a significant effect on several cortical bone parameters and enhanced bone mechanical properties in LF but not HF fed mice. Microbiome analyses indicated that exercise altered the HF induced changes in microbial composition by reducing the Firmicutes/Bacteriodetes ratio. This ratio negatively correlated with bone volume as did levels of Clostridia and Lachnospiraceae. In contrast, the abundance of several Actinobacteria phylum members (i.e., Bifidobacteriaceae) were positively correlated with bone volume. Taken together, exercise can prevent many of the negative effects of a high fat diet on male skeletal health. Exercise induced changes in microbiota composition could represent a novel mechanism that contributes to exercise induced benefits to bone health. Copyright © 2018 Elsevier Inc. All rights reserved.

Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training.

PubMed

He, Zihong; Rankinen, Tuomo; Leon, Arthur S; Skinner, James S; Tchernof, André; Bouchard, Claude

2018-03-05

Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program. In the sedentary state, 270 men (29% Blacks) and 304 women (34% Blacks) from the HERITAGE Family Study were available. Among them, 242 men and 238 women completed a 20-week fully standardized exercise program. Fourteen steroid hormones and SHBG concentrations were assayed in a fasted state and were compared for their associations with adiposity in men and women and in response to the exercise program. Covariates adjusted for in partial correlation analysis were age, ancestry, menopause status (women), and oral contraceptives/hormone replacement treatment status (women) at baseline, as well as baseline value of the trait for the training response. Differences among normal weight, overweight, and obese subjects were also considered. Statistical significance was set at P < 0.0001. Baseline levels of dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone-binding globulin (SHBG), and testosterone (TESTO) were negatively associated with fat mass and abdominal fat (P < 0.0001) in men and for SHBG in women (P < 0.0001). TESTO was not correlated with fat-free mass in men or women, but was significantly associated with % fat-free mass in men. No association was detected between baseline steroid hormone levels and changes in adiposity traits in response to 20 weeks of exercise. In men, low DHT, OHPROG, SHBG, and TESTO were associated with higher adiposity and abdominal and visceral fat. A similar adiposity profile was observed in women with low SHBG.

Exercise Decreases Marrow Adipose Tissue Through ß-Oxidation in Obese Running Mice

PubMed Central

Styner, Maya; Pagnotti, Gabriel M; McGrath, Cody; Wu, Xin; Sen, Buer; Uzer, Gunes; Xie, Zhihui; Zong, Xiaopeng; Styner, Martin A; Rubin, Clinton T; Rubin, Janet

2017-01-01

The relationship between marrow adipose tissue (MAT) and bone health is poorly understood. We used running exercise to ask whether obesity-associated MAT can be attenuated via exercise and whether this correlates with gains in bone quantity and quality. C57BL/6 mice were divided into diet-induced obesity (DIO, n = 14) versus low-fat diet (LFD, n = 14). After 3 months, 16-week-old mice were allocated to an exercise intervention (LFD-E, DIO-E) or a control group (LFD, DIO) for 6 weeks (4 groups, n = 7/group). Marrow adipocyte area was 44% higher with obesity (p<0.0001) and after exercise 33% lower in LFD (p<0.0001) and 39% lower in DIO (p<0.0001). In LFD, exercise did not affect adipocyte number; however, in DIO, the adipocyte number was 56% lower (p<0.0001). MAT was 44% higher in DIO measured by osmium-µCT, whereas exercise associated with reduced MAT (–23% in LFD, –48% in DIO, p<0.05). MAT was additionally quantified by 9.4TMRI, and correlated with osmium-µCT (r = 0.645; p<0.01). Consistent with higher lipid beta oxidation, perilipin 3 (PLIN3) rose with exercise in tibial mRNA (+92% in LFD,+60% in DIO, p<0.05). Tibial µCT-derived trabecular bone volume (BV/TV) was not influenced by DIO but responded to exercise with an increase of 19% (p<0.001). DIO was associated with higher cortical periosteal and endosteal volumes of 15% (p = 0.012) and 35% (p<0.01), respectively, but Ct. Ar/Tt.Ar was lower by 2.4% (p<0.05). There was a trend for higher stiffness (N/m) in DIO, and exercise augmented this further. In conclusion, obesity associated with increases in marrow lipid—measured by osmium-µCT and MRI—and partially due to an increase in adipocyte size, suggesting increased lipid uptake into preexisting adipocytes. Exercise associated with smaller adipocytes and less bone lipid, likely invoking increased ß-oxidation and basal lipolysis as evidenced by higher levels of PLIN3. PMID:28436105

Involuntary wheel running improves but does not fully reverse the deterioration of bone structure of obese rats despite decreasing adiposity

USDA-ARS?s Scientific Manuscript database

Excessive adiposity induced by a high-fat diet is detrimental to bone structure and strength in various animal models. This study investigated whether exercise or anti-oxidant supplementation with vitamin C and E during exercise counteracts bone structure deterioration at different skeletal sites an...

Obesity: genes, glands or gluttony?

PubMed

Chisholm, D J; Samaras, K; Markovic, T; Carey, D; Lapsys, N; Campbell, L V

1998-01-01

Distribution as well as amount of fat has health implications; central abdominal fat seems to be the major contributor to insulin resistance and risk of diabetes, hypertension and cardiovascular disease. Physical activity and diet affect overall adiposity; moreover, exercise specifically reduces visceral fat. The sexes differ in fat distribution; in particular, pre-menopausal women, despite greater overall adiposity, have much less visceral fat than men. There is a strong genetic determination of overall obesity and central abdominal adiposity. Genes regulating obesity (e.g. Ob) could modulate appetite, satiety, metabolic rate or physical activity. Moderate obesity probably results from interaction between genetic predisposition and an environment of abundant calories and reduced physical activity. Single gene mutations are being identified in a few morbidly obese people; however, the common genetic predisposition for obesity may relate to more subtle variations in regulatory controls. Diet and exercise are effective for some, but the response is often disappointing. Definition of pathways controlling appetite, metabolic rate and lipid metabolism may generate improved pharmacological compounds. Education and availability of lower-energy foods may help, but more radical approaches may be needed, such as environmental restructuring to increase physical activity. The problem is great, but failure will mean intolerably increased health costs.

Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice

PubMed Central

Kawanishi, Noriaki; Niihara, Hiroyuki; Mizokami, Tsubasa; Yada, Koichi; Suzuki, Katsuhiko

2015-01-01

The innate immune system is associated with the development of local inflammation. Neutrophils play an essential role in the development of the adipose tissue (AT) inflammation associated with obesity by producing elastase, which can promote the activation and infiltration of macrophages. Exercise training attenuates AT inflammation via suppression of macrophage infiltration. However, the mechanisms driving this phenomenon remains to be elucidated. Here, we evaluated the effects of exercise training on the infiltration of neutrophils and elastase expression in an obese mouse model. Four-week-old male C57BL/6J mice were randomly assigned to one of three groups that either received a normal diet (ND) plus sedentary activity (n = 15), a high-fat diet (HFD) plus sedentary activity (n = 15), or a HFD plus exercise training (n = 15). Mice were fed the ND or HFD from the age of 4 weeks until 20 weeks. Mice in the exercise group ran on a treadmill for 60 min/day, 5 days/week over the same experimental period. Mice fed with the HFD had increased content of macrophages in the AT and increased inflammatory cytokine mRNA levels, which were reduced by exercise training. Similarly, AT from the HFD sedentary mice contained more neutrophils than AT from the ND mice, and the amount of neutrophils in this tissue in HFD-fed mice was lowered by exercise training. The mRNA levels of neutrophil elastase in AT were lower in the HFD exercise-trained mice than those in the HFD sedentary mice. These results suggest that exercise training plays a critical role in reducing macrophage infiltration and AT inflammation by regulating the infiltration of neutrophils. PMID:26341995

Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

PubMed Central

Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Mathai, Michael L.

2016-01-01

Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. Conclusion Ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. PMID:27058737

12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake.

PubMed

Stanford, Kristin I; Lynes, Matthew D; Takahashi, Hirokazu; Baer, Lisa A; Arts, Peter J; May, Francis J; Lehnig, Adam C; Middelbeek, Roeland J W; Richard, Jeffrey J; So, Kawai; Chen, Emily Y; Gao, Fei; Narain, Niven R; Distefano, Giovanna; Shettigar, Vikram K; Hirshman, Michael F; Ziolo, Mark T; Kiebish, Michael A; Tseng, Yu-Hua; Coen, Paul M; Goodyear, Laurie J

2018-05-01

Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise. Copyright © 2018 Elsevier Inc. All rights reserved.

Medium-chain triglycerides are advantageous in promoting weight loss although not beneficial to exercise performance.

PubMed

Clegg, Miriam E

2010-11-01

Medium-chain triglycerides (MCT) are triglycerides with a fatty acid chain length varying between 6 and 10 carbon atoms. MCT differ from long-chain triglycerides as they are relatively soluble in water and, hence, rapidly hydrolysed and absorbed. MCT are transported in the blood through the portal system, consequently they bypass adipose tissue that makes them less susceptible to hormone-sensitive lipase and deposition into adipose tissue stores. Due to these properties, MCT have been researched for both benefits to exercise performance and health. The present review aims to assess whether MCT are beneficial in either of these situations. MCT have been proposed as a means to maximizing an athlete's ability to maintain their glycogen stores so they can be more competitive. However, only two studies to date have shown an improvement in exercise performance. From a health perspective, MCT increase fat oxidation and energy expenditure as well as reduce food intake and beneficially alter body composition. Results indicate that MCT feeding is ineffective in improving exercise performance and future work should focus on the health benefits and applications of MCT.

A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

PubMed

Morettini, Micaela; Palumbo, Maria Concetta; Sacchetti, Massimo; Castiglione, Filippo; Mazzà, Claudia

2017-01-01

Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (<10%) was found for each parameter and the physiologically meaningful parameters were all consistent with literature data. Moreover, plasma IL-6 dynamics during exercise and post-exercise were consistent with literature data from exercise protocols differing in intensity, duration and modality. The model successfully emulated the physiological effects of exercise on plasma IL-6 levels and provided a reliable description of the role of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system model here proposed is suitable to simulate IL-6 response to different exercise modalities. Its future integration with existing models of GLP-1-induced insulin secretion might provide a more reliable description of exercise's effects on glucose homeostasis and hence support the definition of more tailored interventions for the treatment of type 2 diabetes.

Serum levels of fatty acid binding protein 4 and fat metabolic markers in relation to catecholamines following exercise.

PubMed

Iso, Tatsuya; Sunaga, Hiroaki; Matsui, Hiroki; Kasama, Shu; Oshima, Naomi; Haruyama, Hikari; Furukawa, Nozomi; Nakajima, Kiyomi; Machida, Tetsuo; Murakami, Masami; Yokoyama, Tomoyuki; Kurabayashi, Masahiko

2017-11-01

Lipolysis is stimulated by activation of adrenergic inputs to adipose tissues. Our recent study showed that serum concentrations of fatty acid binding protein 4 (FABP4) are robustly elevated in patients with acute myocardial infarction and ventricular tachyarrhythmia, that display a marked activation of the sympathetic nervous system (SNS). However, it remains unknown whether circulating FABP4 concentrations are associated with exercise-induced SNS activation. Thirty one healthy volunteers underwent cardiopulmonary exercise testing on a cycle ergometer up to the workload levels below and above anaerobic threshold, low- and high-intensity exercise, respectively. Serial blood samplings were performed before and after exercise. High-intensity exercise significantly increased serum concentrations of FABP4 and catecholamines, and their concentrations declined fast thereafter in a similar fashion. These changes were accompanied by little, if any, changes in other metabolic markers. Regardless of adiposity, percent change from baseline to peak FABP4 levels (%FABP4) was comparable in all subjects. Stepwise regression analysis revealed that %FABP4 was highly correlated with that in norepinephrine. Our study reveals the significant correlation between circulating FABP4 and norepinephrine levels during exercise testing. Together with the fact that FABP4 is secreted from adipocytes via β-adrenergic-mediated lipolytic mechanisms, this study suggests FABP4 as a potential biomarker for adrenergic overdrive. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity - A randomized trial.

PubMed

Winn, Nathan C; Liu, Ying; Rector, R Scott; Parks, Elizabeth J; Ibdah, Jamal A; Kanaley, Jill A

2018-01-01

Exercise training is commonly prescribed for individuals diagnosed with nonalcoholic fatty liver disease (NAFLD); however, consensus regarding the volume and intensity of exercise for optimal benefits is lacking. Thus, we determined whether high intensity interval exercise training (HIIT) produced greater reductions in intrahepatic lipid (IHL) content and NAFLD risk factors compared with energy-matched moderate intensity continuous exercise training (MICT) in obese adults with liver steatosis. Eighteen obese adults were randomized to either 4weeks of HIIT (4min 80% VO 2 peak/3min, 50% VO 2 peak) or MICT (55% VO 2 peak, ~60min), matched for energy expenditure (~400kcal/session) and compared to five non-exercising age-matched control subjects. IHL was measured by 1 H-MRS and frequent blood samples were analyzed for glucose, insulin, c-peptide, and NEFA levels during a liquid meal test (180min) to characterize metabolic phenotype. Baseline body weight, visceral abdominal adiposity, and fasting insulin concentrations were greater in the MICT vs HIIT group (P<0.05), while IHL was tightly matched between MICT and HIIT subjects (P>0.05), albeit higher than control subjects (P<0.01). Visceral abdominal adiposity, body mass, liver aminotransferases (ALT, AST), and hepatic apoptotic/inflammatory markers (cytokeratin 18 and fetuin a) were not reduced with either exercise training intervention (P>0.05). Both HIIT and MICT lowered IHL (HIIT, -37.0±12.4%; MICT, -20.1±6.6%, P<0.05); however, the reduction in IHL was not statistically different between exercise intensities (P=0.25). Furthermore, exercise training decreased postprandial insulin, c-peptide, and lipid peroxidation levels (iAUC, P<0.05). Collectively, these findings indicate that energy-matched high intensity and moderate intensity exercise are effective at decreasing IHL and NAFLD risk that is not contingent upon reductions in abdominal adiposity or body mass. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats.

PubMed

Gao, Ya; Wang, Changjiang; Pan, Tianrong; Luo, Li

2014-02-01

Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.

Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome
.

PubMed

Rubin, Daniela A; Clark, Susan J; Haqq, Andrea M; Castner, Diobel M; Ng, Jason; Judelson, Daniel A

2017-01-01

Prader-Willi syndrome (PWS) is characterized by excessive adiposity. Excess adiposity negatively affects hormonal and metabolic responses to aerobic exercise. This study determined whether PWS and/or adiposity affected hormonal and metabolic responses to resistance exercise. Eleven children with PWS (11.4 ± 3.1 years, 43.9 ± 7.5% body fat), 12 lean children (9.3 ± 1.4 years, 18.3 ± 4.9% body fat), and 13 obese children (9.6 ± 1.3 years, 40.3 ± 5.2% body fat) participated. The children stepped onto an elevated platform while wearing a weighted vest for 6 sets of 10 repetitions per leg (sets separated by 1 min of rest). For the children with PWS, the platform height was 23.0 cm and vest load was computed as (20% of stature × 50% of lean body mass)/23.0 cm. For the controls, the platform height was 20% of the stature and vest load 50% of the lean body mass. Blood samples were obtained before, immediately after, and during recovery from exercise (+15, +30, and +60 min). All groups had similar catecholamine, insulin, and glucagon responses. The groups showed no major differences in glucose and lactate levels. The PWS children demonstrated earlier increases in fatty acids during recovery and higher glycerol and ketone levels than the controls. The PWS children demonstrated largely intact hormonal, glycolytic, and lipolytic responses to lower-body resistance exercise. In PWS, elevated ketone levels suggest an incomplete fat oxidation.
. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.

PubMed

Langbein, Heike; Hofmann, Anja; Brunssen, Coy; Goettsch, Winfried; Morawietz, Henning

2015-05-01

Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Secular Changes of Adiposity and Motor Development in Czech Preschool Children: Lifestyle Changes in Fifty-Five Year Retrospective Study

PubMed Central

Sedlak, Petr; Pařízková, Jana; Daniš, Robert; Dvořáková, Hana; Vignerová, Jana

2015-01-01

Secular trends of adiposity and motor development in preschool children since the fifties of the last century up to the beginning of this millennium were analyzed so as to reveal possible changes due to continuously differentiating lifestyle. In preschool children (n = 3678) height, weight, skinfold thickness over triceps, subscapular, and suprailiac were measured by Harpenden caliper in 1957, 1977, 1980, 1985, 1990, and 2012. Simultaneously, motor performance was tested by evaluating the achievements in broad jump and throwing a ball, as a marker of adaptation to changing level of physical activity, free games, and exercise. Along the period of five decades the values of skinfold thickness increased significantly until 2012, mainly on the trunk. Simultaneously, the level of motor performance significantly decreased. Modifications of the way of life during the mentioned five decades characterized by sedentarism and inadequate food intake as related to energy output influenced negatively both adiposity and motor performance already in preschool children. Mostly increased deposition of fat on the trunk which is considered as a marker of possible development of metabolic syndrome was apparent already in preschool age, indicating the importance of early intervention concerning also physical activity and availability for exercise since early life. PMID:26380296

Effects of a12-week endurance exercise program on adiposity and flexibility of Nigerian perimenopausal and postmenopausal women.

PubMed

Ogwumike, O O; Arowojolu, A O; Sanya, A O

2011-12-20

Menopause is a sign of aging in the woman. Loss of ovarian function induces a reduction in resting metabolic rate, physical energy expenditure, fat-free mass and abdominal adipose tissue accumulation. Location of adipose tissue deposit in abdominal region plays an important role in occurrence of hyperlipidemia, diabetes, hypertension and atherosclerosis. Although regular participation in physical exercise have been suggested to improve adiposity and body flexibility which are important health related components of physical fitness, few published studies are available on the effect of exercise on Nigerian menopausal women. This study investigated effects of a twelve-week endurance exercise program (EEP) on central and abdominal obesity as well as flexibility of perimenopausal and postmenopausal Nigerian women. The study employed a pretest- posttest control group design comprising a sample of 175 apparently healthy, literate, sedentary women within age range 40-59 years. They were workers in state and federal establishments in Ibadan North Local Government Area of Oyo State, Nigeria. Based on history of their last menstrual period, women with regular or irregular menstrual cycle status were allocated into perimenopausal group and those who no longer menstruated into postmenopausal group. A table of random numbers was used for further allocation into perimenopausal exercise group (PEMEG, 45), postmenopausal exercise group (POMEG, 45) perimenopausal control group (PEMCG, 42) and postmenopausal control group (POMCG, 43). Waist Hip Ratio (WHR), Body Mass Index (BMI) as well as Hip and Trunk Flexibility (HTF) were evaluated at baseline and 4weekly intervals until end of 12th week. EEP consisted of a 10-station circuit of cardiovascular endurance, flexibility, coordination, abdominal and pelvic floor muscle exercises. Data were analyzed using descriptive and inferential statistics. Mean age of participants was 52.3±4.1 years, 95% C.I (51.64-52.88) years. Significant reduction occurred between baseline and end of 12th week mean values of WHR in PEMEG (0.86 ± 0.08 vs 0.71 ± 0.07)and POMEG groups (0.88± 0.06 vs0.77 ± 0.07) while significant increases were observed between baseline values and end of 12th week mean values of HTF in PEMEG (18.84 ± 4.23vs28.27± 3.82) and POMEG (19.51 ± 4.02vs25.97± 2.36) (p<0.05). Significant changes did not occur in BMI in both groups even though mean differences were observed in baseline values compared with end of 12th week mean values of these variables. In PEMCG and POMCG groups, there were no observable changes in mean values of WHR, BMI and HTF from baseline to end of study. Participation in endurance exercise program is essential for perimenopausal and postmenopausal Nigerian women for improved central and abdominal adiposity as well as flexibility.

[Immunometabolism of exercise and sedentary lifestyle].

PubMed

Moreno-Eutimio, Mario Adán; Acosta-Altamirano, Gustavo

2014-01-01

Sedentary lifestyle leads to the accumulation of visceral fat. This is accompanied by the infiltration of immune cells with pro-inflammatory characteristics in adipose tissue, causing an increased release of cytokines and generating a low-grade inflammatory state. It has been associated with the development of insulin resistance, atherosclerosis, neurodegeneration, and development of tumors. Exercise can be used as a treatment to improve symptoms of many of these conditions because it promotes an anti-inflammatory effect. In this review we analyze the pro-inflammatory factors present in obesity and the induction of antiinflammatory factors that occur with exercise.

Endurance exercise training induces fat depot-specific differences in basal autophagic activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Goki; Kato, Hisashi; Izawa, Tetsuya, E-mail: tizawa@mail.doshisha.ac.jp

The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly highermore » in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased autophagosome associated LC3-II in WAT. • Exercise-induced changes in p62 and ATG7 were WAT-type specific. • Exercise-induced basal autophagic activity shows fat depot-specific differences.« less

Rationale, design, methodology and sample characteristics for the family partners for health study: a cluster randomized controlled study

PubMed Central

2012-01-01

Background Young children who are overweight are at increased risk of becoming obese and developing type 2 diabetes and cardiovascular disease later in life. Therefore, early intervention is critical. This paper describes the rationale, design, methodology, and sample characteristics of a 5-year cluster randomized controlled trial being conducted in eight elementary schools in rural North Carolina, United States. Methods/Design The first aim of the trial is to examine the effects of a two-phased intervention on weight status, adiposity, nutrition and exercise health behaviors, and self-efficacy in overweight or obese 2nd, 3 rd, and 4th grade children and their overweight or obese parents. The primary outcome in children is stabilization of BMI percentile trajectory from baseline to 18 months. The primary outcome in parents is a decrease in BMI from baseline to 18 months. Secondary outcomes for both children and parents include adiposity, nutrition and exercise health behaviors, and self-efficacy from baseline to 18 months. A secondary aim of the trial is to examine in the experimental group, the relationships between parents and children's changes in weight status, adiposity, nutrition and exercise health behaviors, and self-efficacy. An exploratory aim is to determine whether African American, Hispanic, and non-Hispanic white children and parents in the experimental group benefit differently from the intervention in weight status, adiposity, health behaviors, and self-efficacy. A total of 358 African American, non-Hispanic white, and bilingual Hispanic children with a BMI ≥ 85th percentile and 358 parents with a BMI ≥ 25 kg/m2 have been inducted over 3 1/2 years and randomized by cohort to either an experimental or a wait-listed control group. The experimental group receives a 12-week intensive intervention of nutrition and exercise education, coping skills training and exercise (Phase I), 9 months of continued monthly contact (Phase II) and then 6 months (follow-up) on their own. Safety endpoints include adverse event reporting. Intention-to-treat analysis will be applied to all data. Discussion Findings from this trial may lead to an effective intervention to assist children and parents to work together to improve nutrition and exercise patterns by making small lifestyle pattern changes. Trial registration NCT01378806. PMID:22463125

Zinc-α2-glycoprotein expression in adipose tissue of obese postmenopausal women before and after weight loss and exercise + weight loss.

PubMed

Ge, Shealinna; Ryan, Alice S

2014-08-01

Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX + WL) on ZAG expression. A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25-46 kg/m(2)) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR. Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r = -0.50, P < 0.005), sagittal diameter (r = -0.42, P < 0.05), and positively related to VO(2)max (r = 0.37, P < 0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r = -0.39 to -0.50, all P < 0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX + WL and WL. Abdominal ZAG expression may be important in central fat accumulation and fitness but only modestly increase (nonsignificantly) with weight reduction alone or with aerobic training in obese postmenopausal women. Published by Elsevier Inc.

Zinc-α2-Glycoprotein Expression in Adipose Tissue of Obese Postmenopausal Women before and after Weight Loss with and without Exercise

PubMed Central

Ge, Shealinna; Ryan, Alice S.

2014-01-01

Objective Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX+WL) on ZAG expression. Design and Methods A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25–46 kg/m2) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX+WL (n=17) and WL (n=16). ZAG expression was determined by RT-PCR. Results Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r=−0.50, P<0.005), sagittal diameter (r=−0.42, P<0.05), and positively related to VO2max (r=0.37, P<0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r=−0.39 to −0.50, all P<0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX+WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX+WL and WL. Conclusions Abdominal ZAG expression may be important in central fat accumulation and fitness that modestly but not significantly increases with weight reduction alone or with aerobic training in obese postmenopausal women. PMID:24929893

Differential Effects of Bariatric Surgery Versus Exercise on Excessive Visceral Fat Deposits

PubMed Central

Wu, Fu-Zong; Huang, Yi-Luan; Wu, Carol C.; Wang, Yen-Chi; Pan, Hsiang-Ju; Huang, Chin-Kun; Yeh, Lee-Ren; Wu, Ming-Ting

2016-01-01

Abstract The aim of the present study was to compare differential impacts of bariatric surgery and exercise-induced weight loss on excessive abdominal and cardiac fat deposition. Excessive fat accumulation around the heart may play an important role in the pathogenesis of cardiovascular disease. Recent evidences have suggested that bariatric surgery results in relatively less decrease in epicardial fat compared with abdominal visceral fat and paracardial fat. Sixty-four consecutive overweight or obese subjects were enrolled in the study. Clinical characteristics and metabolic profiles were recorded. The volumes of abdominal visceral adipose tissue (AVAT), abdominal subcutaneous adipose tissue (ASAT), epicardial (EAT), and paracardial adipose tissue (PAT) were measured by computed tomography in the bariatric surgery group (N = 25) and the exercise group (N = 39) at baseline and 3 months after intervention. Subjects in both the surgery and exercise groups showed significant reduction in body mass index (15.97%, 7.47%), AVAT (40.52%, 15.24%), ASAT (31.40, 17.34%), PAT (34.40%, 12.05%), and PAT + EAT (22.31%, 17.72%) (all P < 0.001) after intervention compared with baseline. In both the groups, the decrease in EAT was small compared with the other compartments (P < 0.01 in both groups). Compared with the exercise group, the surgery group had greater loss in abdominal and cardiac visceral adipose tissue (AVAT, ASAT, PAT, EAT+PAT) (P < 0.001), but lesser loss in EAT (P = 0.037). Compared with the exercise group, bariatric surgery results in significantly greater percentage loss of excessive fat deposits except for EAT. EAT, but not PAT, was relatively preserved despite weight reduction in both the groups. The physiological impact of persistent EAT deserves further investigation. PMID:26844473

Behavioral and psychosocial correlates of adiposity and healthy lifestyle in Asian Indians.

PubMed

Weber, Mary Beth; Ranjani, Harish; Anjana, Ranjit Mohan; Mohan, Viswanathan; Narayan, K M Venkat; Gazmararian, Julie A

2015-12-01

Adiposity is an important diabetes risk factor, and Asian Indians have elevated diabetes risk. This analysis assessed the relationship between behavioral and psychosocial factors and adiposity among Asian Indians to better understand factors driving elevated weight/waist circumference in this population. This study used screening data (N=1285) from the D-CLIP study, a randomized controlled diabetes prevention trial in Chennai, India. Correlation tests and linear regression models were done to describe relationships among exposure variables (weight loss/exercise self-efficacy, fruit/vegetable intake, weekly exercise, past weight loss experience) and between these exposures and BMI or waist circumference. Exercise and weight loss self-efficacy were positively correlated with average minutes per week exercising (R=0.26, p<0.0001) and fruit (R=0.07, p<0.05) and vegetable intake (R=0.12, p<0.0001). Weekly fruit consumption, past weight loss experience, and weight loss self-efficacy, along with sex, age, and marital status, explained 13.6% and 25.9% in the variation in BMI and waist circumference, respectively. Low fruit consumption, unsuccessful past weight loss attempts, and low self-efficacy for weight loss are associated with higher BMI and waist circumference in this population. Understanding factors related to adiposity is important for preventing and treating weight gain. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

PubMed Central

Koh, Ho-Jin; Hirshman, Michael F.; He, Huamei; Li, Yangfeng; Manabe, Yasuko; Balschi, James A.; Goodyear, Laurie J.

2007-01-01

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis. PMID:17253964

Preferential reductions in intermuscular and visceral adipose tissue with exercise-induced weight loss compared with calorie restriction

PubMed Central

Murphy, Joan C.; McDaniel, Jennifer L.; Mora, Katherine; Villareal, Dennis T.; Fontana, Luigi

2012-01-01

Intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) are associated with insulin resistance. We sought to determine whether exercise-induced weight loss (EX) results in greater reductions in IMAT and VAT compared with similar weight loss induced by calorie restriction (CR) and whether these changes are associated with improvements in glucoregulation. Sedentary men and women (50–60 yr; body mass index of 23.5–29.9 kg/m2) were randomized to 1 yr of CR (n = 17), EX (n = 16), or a control group (CON; n = 6). Bilateral thigh IMAT and VAT volumes were quantified using multi-slice magnetic resonance imaging. Insulin sensitivity index (ISI) was determined from oral glucose tolerance test glucose and insulin levels. Weight loss was comparable (P = 0.25) in the CR (−10.8 ± 1.4%) and EX groups (−8.3 ± 1.5%) and greater than in the control group (−2.0 ± 2.4%; P < 0.05). IMAT and VAT reductions were larger in the CR and EX groups than in the CON group (P ≤ 0.05). After controlling for differences in total fat mass change between the CR and EX groups, IMAT and VAT reductions were nearly twofold greater (P ≤ 0.05) in the EX group than in the CR group (IMAT: −45 ±5 vs. −25 ± 5 ml; VAT: −490 ± 64 vs. −267 ± 61 ml). In the EX group, the reductions in IMAT were correlated with increases in ISI (r = −0.71; P = 0.003), whereas in the CR group, VAT reductions were correlated with increases in ISI (r = −0.64; P = 0.006). In conclusion, calorie restriction and exercise-induced weight loss both decrease IMAT and VAT volumes. However, exercise appears to result in preferential reductions in these fat depots. PMID:22016371

Effects of acute exercise on postprandial triglyceride response after a high-fat meal in overweight black and white adolescents.

PubMed

Lee, S; Burns, S F; White, D; Kuk, J L; Arslanian, S

2013-07-01

We examined the effects of acute exercise on postprandial triglyceride (TG) metabolism following a high-fat meal in overweight black vs white adolescents. Twenty-one black and 17 white adolescents (12-18 yrs, body mass index 85th percentile) were evaluated twice, during control versus exercise trials, 1-4 weeks apart, in a counterbalanced randomized design. In the control trial, participants performed no exercise on day 1. In the exercise trial, participants performed a single bout of 60-min exercise (50% VO2 peak) on a cycle ergometer on day 1. On day 2 of both trials, participants consumed a high-fat breakfast (70% calories from fat) and blood was sampled for TG concentration in the fasted state and for 6 h postprandially. There was a significant main effect of condition on postprandial peak TG concentration (P=0.01) and TG area under the curve (AUC) (P=0.003), suggesting that independent of race, peak TG and TG-AUC was lower in the exercise trial vs control trial. Including Tanner stage, gender, total fat (kg) and visceral adipose tissue (VAT) as independent variables, stepwise multiple regression analyses revealed that in whites, VAT was the strongest (P<0.05) predictor of postprandial TG-AUC, explaining 56 and 25% of the variances in TG-AUC in the control and exercise trials, respectively. In blacks, VAT was not associated with postprandial TG-AUC, independent of trial. A single bout of aerobic exercise preceding a high-fat meal is beneficial to reduce postprandial TG concentrations in overweight white adolescents to a greater extent than black adolescents, particularly those with increased visceral adiposity.

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity

PubMed Central

Garcia, Emmanuel; Becker, Veronika G. C.; McCullough, Danielle J.; Stabley, John N.; Gittemeier, Elizabeth M.; Opoku-Acheampong, Alexander B.; Sieman, Dietmar W.

2016-01-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10−9 to 10−4 M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. PMID:27125846

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

PubMed

Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

2016-07-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

Resistance to Aerobic Exercise Training Causes Metabolic Dysfunction and Reveals Novel Exercise-Regulated Signaling Networks

PubMed Central

Lessard, Sarah J.; Rivas, Donato A.; Alves-Wagner, Ana B.; Hirshman, Michael F.; Gallagher, Iain J.; Constantin-Teodosiu, Dumitru; Atkins, Ryan; Greenhaff, Paul L.; Qi, Nathan R.; Gustafsson, Thomas; Fielding, Roger A.; Timmons, James A.; Britton, Steven L.; Koch, Lauren G.; Goodyear, Laurie J.

2013-01-01

Low aerobic exercise capacity is a risk factor for diabetes and a strong predictor of mortality, yet some individuals are “exercise-resistant” and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease risk, we used selective breeding for 15 generations to develop rat models of low and high aerobic response to training. Before exercise training, rats selected as low and high responders had similar exercise capacities. However, after 8 weeks of treadmill training, low responders failed to improve their exercise capacity, whereas high responders improved by 54%. Remarkably, low responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise-resistant phenotype segregates with disease risk. Low responders had impaired exercise-induced angiogenesis in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low responders. Low responders had increased stress/inflammatory signaling and altered transforming growth factor-β signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system, we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease. PMID:23610057

The skeletal and heart muscle triacylglycerol lipolysis revisited.

PubMed

Knapp, M; Gorski, J

2017-02-01

For 40 years, the enzyme hormone sensitive lipase was considered to hydrolyze the first ester bond of the triacylglycerol moiety and thus initiate hydrolysis. However, 12 years ago a new lipolytic enzyme, termed adipose triglyceride lipase was discovered. It was further shown that the process of lipolysis of triacylglycerol to diacylglycerol and fatty acid is initiated by adipose triglyceride lipase and not by hormone sensitive lipase, responsible for hydrolysis of diacylglycerol to monoacyglycerol and fatty acid. Adipose triglyceride lipase is present in all types of cells containing neutral fat. The enzyme is activated by a protein called comparative gene identification-58 and inhibited by a protein called G0/G1 switch protein 2. It has also been discovered that perilipins, the main proteins coating lipid droplets in the cells, are involved in the process of triacylglycerol lipolysis. Five perilipins (1-5) were identified, however, up to now their role has been poorly assessed. In skeletal muscles, exercise and training affect the mRNA expression and protein content of adipose triglyceride lipase, comparative gene identification-58, G0/G1 switch protein 2, perilipin 2 and 5. The effect of exercise/training depends on exercise intensity and type of muscle fiber. An interaction between comparative gene identification-58 and adipose triglyceride lipase seems to be responsible for the enzyme activation during contractile activity. Adipose triglyceride lipase is also responsible for the activation of the first step of triacylglycerol lipolysis in the heart. There is substantial evidence that cardiac triacylglycerol metabolism affects the function of the heart. ATGL gene mutations leads to the development of neutral lipid storage diseases.

Homocysteine, visceral adiposity-related novel cardiometabolic risk factors, and exaggerated blood pressure response to the exercise treadmill test.

PubMed

Türker Duyuler, Pinar; Duyuler, Serkan; Demir, Mevlüt; Uçar Elalmiş, Özgül; Güray, Ümit; İleri, Mehmet

2017-12-01

Exaggerated blood pressure response to exercise is a risk factor for the development of future hypertension. In this study, we aimed to investigate the association between homocysteine, epicardial fat thickness, nonalcoholic hepatic steatosis, and exaggerated blood pressure response to exercise. We included 44 normotensive and 40 patients with exaggerated blood pressure response to exercise who have normal resting blood pressure and without a previous diagnosis of hypertension. All patients underwent treadmill exercise test and clinical, ultrasonographic, and echocardiographic evaluation. Exaggerated blood pressure response to exercise is defined as peak exercise systolic blood pressure of at least 210 mmHg in men and at least 190 mmHg in women. Homocysteine and other biochemical parameters were determined with standardized automated laboratory tests. Mean age of all participants is 47.9±8.5 years, and 36 of 84 participants were female. The frequency of diabetes mellitus in both groups was similar (P=0.250). Homeostasis model assessment index-insulin resistance had a statistically insignificant trend to be higher in a patient with exercise hypertension (P=0.058). The nonalcoholic fatty liver was more frequent in patients with exercise hypertension (13.6 vs. 47.5%, P=0.002). Epicardial fat thickness was increased in patients with exercise hypertension (5.5±1.5 vs. 7.3±1.1 mm; P=0.001). However, homocysteine levels did not significantly differ between normotensive and exercise hypertensive patients [12.3 μmol/l (5.7-16.9 μmol/l) vs. 13 μmol/l (5.9-28.3 μmol/l); P=0.883]. In our study, homocysteine levels were not associated with exaggerated blood pressure response to exercise; however, fatty liver and epicardial fat thickness as visceral adiposity-related cardiometabolic risk factors were significantly related with exaggerated blood pressure response to exercise in patients without a previous diagnosis of hypertension.

Calorie Restriction in Overweight SeniorS: Response of Older Adults to a Dieting Study: The CROSSROADS Randomized Controlled Clinical Trial

PubMed Central

Haas, Marilyn C.; Bodner, Eric V.; Brown, Cynthia J.; Bryan, David; Buys, David R.; Keita, Akilah Dulin; Flagg, Lee Anne; Goss, Amy; Gower, Barbara; Hovater, Martha; Hunter, Gary; Ritchie, Christine S.; Roth, David L.; Wingo, Brooks C.; Ard, Jamy; Locher, Julie L.

2014-01-01

We conducted a study designed to evaluate whether the benefits of intentional weight loss exceed the potential risks in a group of community-dwelling, obese, older adults who were at increased risk for cardiometabolic disease. The CROSSROADS trial used a prospective randomized controlled design to compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition and adipose tissue deposition (Specific Aim #1: To compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition, namely visceral adipose tissue (VAT)), cardiometabolic disease risk (Specific Aim #2: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on cardiometabolic disease risk), functional status and quality of life (Specific Aim #3: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on functional status and quality of life). Participants were randomly assigned to one of three groups: Exercise Only (Control) Intervention, Exercise + Diet Quality + Weight Maintenance Intervention, or Exercise + Diet Quality + Weight Loss Intervention. CROSSROADS utilized a lifestyle intervention approach consisting of exercise, dietary, and behavioral components. The development and implementation of the CROSSROADS protocol, including a description of the methodology, detailing specific elements of the lifestyle intervention, assurances of treatment fidelity, and participant retention; outcome measures and adverse event monitoring; as well as unique data management features of the trial results, are presented in this article. PMID:25424512

Calorie restriction in overweight seniors: response of older adults to a dieting study: the CROSSROADS randomized controlled clinical trial.

PubMed

Haas, Marilyn C; Bodner, Eric V; Brown, Cynthia J; Bryan, David; Buys, David R; Keita, Akilah Dulin; Flagg, Lee Anne; Goss, Amy; Gower, Barbara; Hovater, Martha; Hunter, Gary; Ritchie, Christine S; Roth, David L; Wingo, Brooks C; Ard, Jamy; Locher, Julie L

2014-01-01

We conducted a study designed to evaluate whether the benefits of intentional weight loss exceed the potential risks in a group of community-dwelling obese older adults who were at increased risk for cardiometabolic disease. The CROSSROADS trial used a prospective randomized controlled design to compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition and adipose tissue deposition (Specific Aim #1: To compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition, namely visceral adipose tissue), cardiometabolic disease risk (Specific Aim #2: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on cardiometabolic disease risk), and functional status and quality of life (Specific Aim #3: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on functional status and quality of life). Participants were randomly assigned to one of three groups: Exercise Only (Control) Intervention, Exercise + Diet Quality + Weight Maintenance Intervention, or Exercise + Diet Quality + Weight Loss Intervention. CROSSROADS utilized a lifestyle intervention approach consisting of exercise, dietary, and behavioral components. The development and implementation of the CROSSROADS protocol, including a description of the methodology, detailing specific elements of the lifestyle intervention, assurances of treatment fidelity, and participant retention; outcome measures and adverse event monitoring; as well as unique data management features of the trial results, are presented in this article.

Effects of exercise and heat stress on regional blood flow in pregnant sheep.

PubMed

Bell, A W; Hales, J R; Fawcett, A A; King, R B

1986-05-01

Radioactive microspheres were used to measure cardiac output and blood flow to most major tissues, including those in the pregnant uterus, in late-pregnant ewes at rest and during treadmill exercise (approximately 3-fold increase in metabolic rate for 30 min) in thermoneutral (TN) (dry bulb temperature (Tdb) = 13 degrees C, wet bulb temperature (Twb) = 10 degrees C) and mildly hot (MH) (Tdb = 40 degrees C, Twb = 27 degrees C) environments. Exercise caused major increases in blood flow to respiratory muscles, nonrespiratory limb muscles, and adipose tissue, and flow was decreased to some gastrointestinal tissues, spleen, pancreas, and to placental and nonplacental tissues in the pregnant uterus. Heat exposure had relatively little effect on these exercise-induced changes, except that flow was further increased in the respiratory muscles. Results are compared with those of a similar study on nonpregnant sheep in which changes in muscle, skin, and visceral flows during exercise were attenuated by heat exposure. It is suggested that redistribution of blood flow from the pregnant uterus, which in resting ewes took 22% of cardiac output, is a significant buffer against the potentially deleterious effects of combined exercise and heat stress on blood flow to exercising muscles and thermoregulatory tissues.

Acute aerobic exercise differentially alters acylated ghrelin and perceived fullness in normal-weight and obese individuals.

PubMed

Heden, Timothy D; Liu, Ying; Park, Youngmin; Dellsperger, Kevin C; Kanaley, Jill A

2013-09-01

Adiposity alters acylated ghrelin concentrations, but it is unknown whether adiposity alters the effect of exercise and feeding on acylated ghrelin responses. Therefore, the purpose of this study was to determine whether adiposity [normal-weight (NW) vs. obese (Ob)] influences the effect of exercise and feeding on acylated ghrelin, hunger, and fullness. Fourteen NW and 14 Ob individuals completed two trials in a randomized counterbalanced fashion, including a prior exercise trial (EX) and a no exercise trial (NoEX). During the EX trial, the participants performed 1 h of treadmill walking (55-60% peak O2 uptake) during the evening, 12 h before a 4-h standardized mixed meal test. Frequent blood samples were taken and analyzed for acylated ghrelin, and a visual analog scale was used to assess perceived hunger and fullness. In NW individuals, EX, compared with NoEX, reduced fasting acylated ghrelin concentrations by 18% (P = 0.03), and, in response to feeding, the change in acylated ghrelin (P = 0.02) was attenuated by 39%, but perceived hunger and fullness were unaltered. In Ob individuals, despite no changes in fasting or postprandial acylated ghrelin concentrations with EX, postprandial fullness was attenuated by 46% compared with NoEX (P = 0.05). In summary, exercise performed the night before a meal suppresses acylated ghrelin concentrations in NW individuals without altering perceived hunger or fullness. In Ob individuals, despite no changes in acylated ghrelin concentrations, EX reduced the fullness response to the test meal. Acylated ghrelin and perceived fullness responses are differently altered by acute aerobic exercise in NW and Ob individuals.

Aerobic exercise and other healthy lifestyle factors that influence vascular aging.

PubMed

Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R

2014-12-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. Copyright © 2014 The American Physiological Society.

Aerobic exercise and other healthy lifestyle factors that influence vascular aging

PubMed Central

Santos-Parker, Jessica R.; LaRocca, Thomas J.

2014-01-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote “resistance” against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. PMID:25434012

Diet and diet combined with chronic aerobic exercise decreases body fat mass and alters plasma and adipose tissue inflammatory markers in obese women.

PubMed

Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

2013-12-01

The purpose of this study was to investigate the effect of 6 months aerobic exercise and diet alone or in combination on markers of inflammation (MOI) in circulation and in adipose abdominal tissue (AT) in obese women. Thirty obese subjects were randomized into a 24-week intervention: (1) exercise (EX), (2) diet (DI), and (3) exercise and diet (EXD). Blood samples were collected at baseline, after 12 and 24 weeks. AT biopsies were obtained only at baseline and after 24 weeks. In the EXD and DI groups, the fat loss was after 12 weeks was -13.74 and -7.8 % (P < 0.01) and after 24 weeks was -21.82 and -17 % (P < 0.01) with no changes in the EX group. After 12 and 24 weeks, maximal oxygen consumption (VO2max) was increased by 21.81-39.54 % (P < 0.05) in the EXD group and 18.09-40.95 % in the EX group with no changes in the DI group. In the EXD and DI groups, circulating levels of tumor necrosis factor α and interleukin 6 were decreased after 24 weeks for both groups (P < 0.01). No changes in the EX group. Homeostatic model assessment for insulin resistance decreased (P < 0.05) only after 24 weeks in the EXD group. In AT biopsies, subjects in the EXD and DI groups exhibited a significant decrease in MO (P < 0.01 for all). No changes in AT biopsies were found in the EX group. In conclusion, chronic aerobic exercise was found to have no effects on circulating and AT MOI despite an increased VO2max. Rather important body composition modifications were found to have beneficial effects on circulating and AT MOI in these obese women.

Aerobic exercise is necessary to improve glucose utilization with moderate weight loss in women.

PubMed

Ryan, Alice S; Nicklas, Barbara J; Berman, Dora M

2006-06-01

To determine the effects of weight loss (WL) alone and combined with aerobic exercise on visceral adipose tissue (VAT), intramuscular fat, insulin-stimulated glucose uptake, and the rate of decline in free fatty acid (FFA) concentrations during hyperinsulinemia. We studied 33 sedentary, obese (BMI = 32 +/- 1 kg/m(2)) postmenopausal women who completed a 6-month (three times per week) program of either WL alone (n = 16) or WL + aerobic exercise (AEX) (n = 17). Glucose utilization (M) was measured during a 3-hour hyperinsulinemic-euglycemic clamp (40 mU/m(2) per minute). M/I, the amount of glucose metabolized per unit of plasma insulin (I), was used as an index of insulin sensitivity. Body weight, total fat mass, and percentage fat decreased similarly in both groups (p < 0.01). VAT, subcutaneous abdominal adipose tissue, mid-thigh subcutaneous fat, and intramuscular fat decreased to a similar extent in both groups and between 14% and 27% after WL and WL+AEX (p < 0.05). WL alone did not change M or M/I; however, M and M/I increased 15% and 21% after WL+AEX (p < 0.05). Fasting concentrations and rate of decline of FFA did not change in either group. In stepwise regression models to determine the independent predictors of changes in M and M/I, the change in VAT was the single independent predictor of M (r(2) = 0.30) and M/I (r(2) = 0.33). Intramuscular fat decreases similarly with 6 months of moderate WL alone or with aerobic exercise in postmenopausal women. In contrast, only WL combined with exercise results in increased glucose utilization and insulin sensitivity. These findings should be validated in a larger population.

Exercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysis.

PubMed

Sabag, A; Way, K L; Keating, S E; Sultana, R N; O'Connor, H T; Baker, M K; Chuter, V H; George, J; Johnson, N A

2017-06-01

Ectopic adipose tissue surrounding the intra-abdominal organs (visceral fat) and located in the liver, heart, pancreas and muscle, is linked to cardio-metabolic complications commonly experienced in type 2 diabetes. A systematic review and meta-analysis was performed to determine the effect of exercise on ectopic fat in adults with type 2 diabetes. Relevant databases were searched to February 2016. Included were randomised controlled studies, which implemented≥4 weeks of aerobic and/or resistance exercise and quantified ectopic fat via magnetic resonance imaging, computed tomography, proton magnetic resonance spectroscopy or muscle biopsy before and after intervention. Risk of bias and study quality was assessed using Egger's funnel plot test and modified Downs and Black checklist, respectively. Of the 10,750 studies retrieved, 24 were included involving 1383 participants. No studies were found assessing the interaction between exercise and cardiac or pancreas fat. One study assessed the effect of exercise on intramyocellular triglyceride concentration. There was a significant pooled effect size for the meta-analysis comparing exercise vs. control on visceral adiposity (ES=-0.21, 95% CI: -0.37 to -0.05; P=0.010) and a near-significant pooled effect size for liver steatosis reduction with exercise (ES=-0.28, 95% CI: -0.57 to 0.01; P=0.054). Aerobic exercise (ES=-0.23, 95% CI: -0.44 to -0.03; P=0.025) but not resistance training exercise (ES=-0.13, 95% CI: -0.37 to 0.12; P=0.307) was effective for reducing visceral fat in overweight/obese adults with type 2 diabetes. These data suggest that exercise effectively reduces visceral and perhaps liver adipose tissue and that aerobic exercise should be a key feature of exercise programs aimed at reducing visceral fat in obesity-related type 2 diabetes. Further studies are required to assess the relative efficacy of exercise modality on liver fat reduction and the effect of exercise on pancreas, heart, and intramyocellular fat in type 2 diabetes and to clarify the effect of exercise on ectopic fat independent of weight loss. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats.

PubMed

da Rocha, Guilherme L; Crisp, Alex H; de Oliveira, Maria R M; da Silva, Carlos A; Silva, Jadson O; Duarte, Ana C G O; Sene-Fiorese, Marcela; Verlengia, Rozangela

2016-01-01

This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats.

Effects of Exercise in the Treatment of Overweight and Obese Children and Adolescents: A Systematic Review of Meta-Analyses

PubMed Central

Kelley, George A.; Kelley, Kristi S.

2013-01-01

Purpose. Conduct a systematic review of previous meta-analyses addressing the effects of exercise in the treatment of overweight and obese children and adolescents. Methods. Previous meta-analyses of randomized controlled exercise trials that assessed adiposity in overweight and obese children and adolescents were included by searching nine electronic databases and cross-referencing from retrieved studies. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. The alpha level for statistical significance was set at P ≤ 0.05. Results. Of the 308 studies reviewed, two aggregate data meta-analyses representing 14 and 17 studies and 481 and 701 boys and girls met all eligibility criteria. Methodological quality was 64% and 73%. For both studies, statistically significant reductions in percent body fat were observed (P = 0.006 and P < 0.00001). The number-needed-to treat (NNT) was 4 and 3 with an estimated 24.5 and 31.5 million overweight and obese children in the world potentially benefitting, 2.8 and 3.6 million in the US. No other measures of adiposity (BMI-related measures, body weight, and central obesity) were statistically significant. Conclusions. Exercise is efficacious for reducing percent body fat in overweight and obese children and adolescents. Insufficient evidence exists to suggest that exercise reduces other measures of adiposity. PMID:24455215

Potential Mechanisms of Exercise in Gestational Diabetes

PubMed Central

Golbidi, Saeid; Laher, Ismail

2013-01-01

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first diagnosed during pregnancy. This condition shares same array of underlying abnormalities as occurs in diabetes outside of pregnancy, for example, genetic and environmental causes. However, the role of a sedentary lifestyle and/or excess energy intake is more prominent in GDM. Physically active women are less likely to develop GDM and other pregnancy-related diseases. Weight gain in pregnancy causes increased release of adipokines from adipose tissue; many adipokines increase oxidative stress and insulin resistance. Increased intramyocellular lipids also increase cellular oxidative stress with subsequent generation of reactive oxygen species. A well-planned program of exercise is an important component of a healthy lifestyle and, in spite of old myths, is also recommended during pregnancy. This paper briefly reviews the role of adipokines in gestational diabetes and attempts to shed some light on the mechanisms by which exercise can be beneficial as an adjuvant therapy in GDM. In this regard, we discuss the mechanisms by which exercise increases insulin sensitivity, changes adipokine profile levels, and boosts antioxidant mechanisms. PMID:23691290

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

PubMed

Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. © 2016 Authors; published by Portland Press Limited.

Soluble Leptin Receptor Predicts Insulin Sensitivity and Correlates With Upregulation of Metabolic Pathways in Men.

PubMed

Sommer, Christine; Lee, Sindre; Gulseth, Hanne Løvdal; Jensen, Jørgen; Drevon, Christian A; Birkeland, Kåre Inge

2018-03-01

Plasma soluble leptin receptor (sOb-R) seems protective of gestational and type 2 diabetes in observational studies, but the mechanisms are unknown. sOb-R is formed by ectodomain shedding of membrane-bound leptin receptors (Ob-Rs), but its associations with messenger RNA (mRNA) expression are scarcely explored. To explore associations between plasma levels of sOb-R and (1) insulin sensitivity, (2) mRNA pathways in adipose tissue and skeletal muscle, and (3) mRNA of candidate genes for sOb-R generation in adipose tissue and skeletal muscle. The MyoGlu study included 26 sedentary, middle-aged men who underwent a 12-week intensive exercise intervention. We measured plasma sOb-R with enzyme-linked immunosorbent assay, insulin sensitivity with a hyperinsulinemic euglycemic clamp, and mRNA in skeletal muscle and adipose tissue with high-throughput sequencing. Baseline plasma sOb-R was strongly associated with baseline glucose infusion rate (GIR) [β (95% confidence interval), 1.19 (0.57 to 1.82) mg/kg/min, P = 0.0006] and GIR improvement after the exercise intervention [0.58 (0.03 to 1.12) mg/kg/min, P = 0.039], also independently of covariates, including plasma leptin. In pathway analyses, high plasma sOb-R correlated with upregulation of metabolic pathways and downregulation of inflammatory pathways in both adipose tissue and skeletal muscle. In skeletal muscle, mRNA of LEPROT and LEPROTL1 (involved in Ob-R cell surface expression) and ADAM10 and ADAM17 (involved sOb-R-shedding) increased after the exercise intervention. Higher plasma sOb-R was associated with improved GIR, upregulation of metabolic pathways, and downregulation of inflammatory pathways, which may be possible mechanisms for the seemingly protective effect of plasma sOb-R on subsequent risk of gestational and type 2 diabetes found in observational studies.

Hormonal and metabolic responses to endurance exercise in children with Prader-Willi syndrome and non-syndromic obesity.

PubMed

Rubin, Daniela A; Clark, Susan J; Ng, Jason; Castner, Diobel M; Haqq, Andrea M; Judelson, Daniel A

2015-03-01

Excess adiposity affects endocrine and metabolic function at rest and during exercise. This study evaluated the endocrine and metabolic responses to exercise in syndromic (Prader-Willi syndrome) and non-syndromic pediatric obesity. Eleven PWS (10.9±1.6 y, 45.4±9.5% body fat), 12 lean (9.4±1.2 y, 17.5±4.6% body fat), and 12 obese (9.2±1.2 y, 39.9±6.8% body fat) children completed ten two-minute cycling exercise bouts, separated by one-minute rest. Blood samples were obtained at rest pre-exercise (PRE), immediately post-exercise (IP), and 15, 30 and 60 minutes into recovery. Samples were analyzed for hormones and metabolites. Growth hormone increased in response to exercise in lean and obese but not PWS (IP>PRE; IP: lean>obese). Epinephrine increased with exercise in lean (IP>PRE), while norepinephrine increased in lean and obese (IP>PRE) but not PWS; no differences were observed between lean and obese groups at IP. No other significant hormonal group interactions existed. Glucose, lactate, free fatty acid, glycerol and ketone responses were similar among groups. PWS children exhibited altered stress hormone responses to exercise. However, glucose-regulating hormones and metabolic responses to exercise appeared normal. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial

USDA-ARS?s Scientific Manuscript database

The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and se...

Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis in the aged

PubMed Central

Camell, Christina D.; Sander, Jil; Spadaro, Olga; Lee, Aileen; Nguyen, Kim Y.; Wing, Allison; Goldberg, Emily L.; Youm, Yun-Hee; Brown, Chester W.; Elsworth, John; Rodeheffer, Matthew S.; Schultze, Joachim L.; Dixit, Vishwa Deep

2017-01-01

Catecholamine-induced lipolysis, the first step in generation of energy substrates through hydrolysis of triglycerides (TGs) 1, declines with age 2,3. The defect in mobilization of free fatty acids (FFA) in elderly is accompanied with increased visceral adiposity, lower exercise capacity, failure to maintain core body temperature during cold stress, and reduced ability to survive starvation. While catecholamine signaling in adipocytes is normal in elderly, how lipolysis is impaired in aging remains unknown 2,4. Here we uncover that the adipose tissue macrophages (ATMs) regulate age-related reduction in adipocyte lipolysis by lowering the bioavailability of norepinephrine (NE). Unexpectedly, unbiased whole transcriptome analyses of adipose macrophages revealed that aging upregulates genes controlling catecholamine degradation in an NLRP3 inflammasome-dependent manner. Deletion of NLRP3 in aging restored catecholamine-induced lipolysis through downregulation of growth differentiation factor-3 (GDF3) and monoamine oxidase-a (MAOA) that is known to degrade NE. Consistent with this, deletion of GDF3 in inflammasome-activated macrophages improved lipolysis by decreasing MAOA and caspase-1. Furthermore, inhibition of MAOA reversed age-related reduction in adipose tissue NE concentration and restored lipolysis with increased levels of key lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Our study reveals that targeting neuro-innate signaling between sympathetic nervous system and macrophages may offer new approaches to mitigate chronic inflammation-induced metabolic impairment and functional decline. PMID:28953873

Vibration Training Triggers Brown Adipocyte Relative Protein Expression in Rat White Adipose Tissue

PubMed Central

Sun, Chao; Zeng, Ruixia; Cao, Ge; Song, Zhibang; Zhang, Yibo; Liu, Chang

2015-01-01

Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group (n = 6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 and inflammatory relative proteins, IL-6 and TNFα. Simultaneously, ATP content and PPARγ protein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve. PMID:26125027

Higher Circulating Leukocytes in Women with PCOS is Reversed by Aerobic Exercise

PubMed Central

Covington, Jeffrey D.; Tam, Charmaine S.; Pasarica, Magdalena; Redman, Leanne M.

2014-01-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r= -0.73, p=0.03; and r= -0.82, p=0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. PMID:25446648

FTO genotype is associated with exercise training-induced changes in body composition

PubMed Central

Rankinen, Tuomo; Rice, Treva; Teran-Garcia, Margarita; Rao, D.C.; Bouchard, Claude

2010-01-01

The fat mass and obesity associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known if regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test if the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO SNP rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (p=0.004) but not in women (p=0.331; gene-by-sex interaction p=0.0053). The FTO genotype was associated with body fat responses to regular exercise (p<0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C-allele showed three times greater fat mass and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity. PMID:19543202

Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats

PubMed Central

da Rocha, Guilherme L.; Crisp, Alex H.; de Oliveira, Maria R. M.; da Silva, Carlos A.; Silva, Jadson O.; Duarte, Ana C. G. O.; Sene-Fiorese, Marcela; Verlengia, Rozangela

2016-01-01

This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb.

PubMed

Heinonen, Ilkka; Wendelin-Saarenhovi, Maria; Kaskinoro, Kimmo; Knuuti, Juhani; Scheinin, Mika; Kalliokoski, Kari K

2013-07-15

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ~40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min(-1)·100 g(-1) in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min(-1)·100 g(-1)) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min(-1)·100 g(-1)). During exercise, NE reduced exercising muscle BF by ~16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT (P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

Lipolytic signaling in response to acute exercise is altered in female mice following ovariectomy

PubMed Central

Wohlers, Lindsay M.; Jackson, Kathryn C.; Spangenburg, Espen E.

2011-01-01

Impaired ovarian function alters lipid metabolism, ultimately resulting in increased visceral fat mass. Currently, we have a poor understanding of alterations in signaling events regulating lipolysis after ovarian function declines. The purpose of this study was to determine if cellular mechanisms regulating lipolysis are altered in mice after ovariectomy (OVX) and if OVX mice exhibit impaired lipolytic signaling when stimulated by acute exercise. SHAM and OVX mice were divided into two groups: control (SHAM cont; OVX cont) or acute treadmill exercise (SHAM ex; OVX ex). The omental/mesenteric (O/M) fat mass of all OVX mice was significantly greater than the SHAM mice. Serum glycerol and blood glucose levels were significantly elevated in OVX cont compared to SHAM cont. Treadmill exercise increased serum glycerol levels only in SHAM mice, with no exercise-induced change detected in OVX mice. NEFA levels were significantly elevated by acute exercise in the SHAM and OVX groups. In O/M fat from both OVX groups there were significant increases in cytosolic ATGL and PLIN2 in the fat cake fraction with concurrent reductions in PLIN1 in the fat cake compared to SHAM. Further, exercise induced significant increases in HSL Ser660 phosphorylation in SHAM mice, but not OVX mice. This suggests that reduced ovarian function has significant effects on critical lipolytic cell signaling mechanisms in O/M adipose tissue. PMID:21815195

Evaluation of markers of beige adipocytes in white adipose tissue of the mouse

USDA-ARS?s Scientific Manuscript database

Beige or brite (brown in white) adipocytes are cells that arise in white adipose tissue (WAT) in response to stimuli like excess energy, exercise, or cold exposure. The induction of beige adipocytes (beigeing) confers resistance to obesity and type-2 diabetes in animal models. There is a growing int...

The impact of physical activity and nutrition on inflammatory bowel disease: the potential role of cross talk between adipose tissue and skeletal muscle.

PubMed

Bilski, J; Mazur-Bialy, A I; Wierdak, M; Brzozowski, T

2013-04-01

Crohn's disease and ulcerative colitis are both chronic inflammatory bowel diseases (IBDs) characterized by a cyclical nature, which alternates between active and quiescent states, ultimately impairing a patients' quality of life. The etiology of IBD is not known but it likely involves a combination of genetic predisposition and environmental risk factors. Physical exercise has been suggested to provide protection against the onset of IBD, but there are inconsistencies in the findings of the published literature. Current research recommends exercise to help counteract some IBD-specific complications and preliminary studies suggest that physical activity may be beneficial in reducing the symptoms of IBD. Obesity is becoming more prevalent in patients diagnosed with IBD and may be associated with higher disease activity. There is evidence that adipokines are involved in the inflammatory and metabolic pathways. Hypertrophy of the mesenteric white adipose tissue has been long recognized as a characteristic feature of Crohn's disease; however its importance is unknown. Recent data suggest that dysregulation of adipokine secretion by white adipose tissue is involved in the pathogenesis of Crohn's disease. Skeletal muscle was shown to produce biologically active myokines, which could be a important contributor to the beneficial effects of exercise. There is mounting evidence for the bi-directional endocrine cross talk between adipose tissue and skeletal muscle. The objective of the present review is to explore the role of exercise and its impact on IBD. Also, we discuss how current discoveries regarding the importance of adipokines and myokines and their cross talk expand our view of the pathological changes and the therapeutic options for IBD.

Effect of different exercise protocols on metabolic profiles and fatty acid metabolism in skeletal muscle in high-fat diet-fed rats.

PubMed

Shen, Youqing; Xu, Xiangfeng; Yue, Kai; Xu, Guodong

2015-05-01

To evaluate the efficacy of mild-intensity endurance, high-intensity interval, and concurrent exercise on preventing high-fat diet-induced obesity. Male rats were divided into five groups, control diet/sedentary group, high-fat diet/sedentary, high-fat diet/endurance exercise, high-fat diet/interval exercise (HI), and high-fat diet/concurrent exercise. All exercise groups were made to exercise for 10 weeks, with matched running distances. Body weight, fat content, blood metabolites, quantitative insulin sensitivity check index (QUICKI), and adipocyte and liver lipid droplet size were assessed, and the expression of fatty acid metabolism-related genes was quantified. All exercise protocols reduced body weight, adiposity, serum triglycerides, and fasting glucose and also improved QUICKI to some extent. However, only HI prevented obesity and its associated pathologies completely. The expression of stearoyl-coenzyme A desaturase-1 was elevated in all rats fed a high-fat diet whereas carnitine palmitoyltransferase 1 (CPT1) expression was increased with exercise. Rev-erbα expression was elevated only in the HI group, which also had the highest level of CPT1 expression. The HI-induced increase in Rev-erbα and CPT1 expression was associated with the complete prevention of diet-induced obesity. Moreover, the increased caloric expenditure achieved with this protocol was preferential over other exercise regimens, and might be used to improve lipid metabolism. © 2015 The Obesity Society.

Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review

PubMed Central

Dinas, Petros C.; Lahart, Ian M.; Timmons, James A.; Svensson, Per-Arne; Koutedakis, Yiannis; Flouris, Andreas D.; Metsios, George S.

2017-01-01

Background: Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Methods: Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. Results: We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. Conclusions: The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews. PMID:28620456

Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor–Deficient Mice

PubMed Central

McGee-Lawrence, Meghan E.; Wenger, Karl H.; Misra, Sudipta; Davis, Catherine L.; Pollock, Norman K.; Elsalanty, Mohammed; Ding, Kehong; Isales, Carlos M.; Hamrick, Mark W.; Wosiski-Kuhn, Marlena; Arounleut, Phonepasong; Mattson, Mark P.; Cutler, Roy G.; Yu, Jack C.

2017-01-01

Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor–deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes. PMID:28323991

Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise

PubMed Central

Styner, Maya; Thompson, William R.; Galior, Kornelia; Uzer, Gunes; Wu, Xin; Kadari, Sanjay; Case, Natasha; Xie, Zhihui; Sen, Buer; Romaine, Andrew; Pagnotti, Gabriel M.; Rubin, Clinton T.; Styner, Martin A.; Horowitz, Mark C.; Rubin, Janet

2014-01-01

Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminish bone quantity, while exercise would slow MAT acquisition and promote bone formation. Eight week-old female C57BL/6 mice were fed a regular (RD) or HFD, and exercise groups were provided voluntary access to running wheels (RD-E, HFD-E). Femoral MAT was assessed by μCT (lipid binder osmium) using a semi-automated approach employing rigid co-alignment, regional bone masks and was normalized for total femoral volume (TV) of the bone compartment. MAT was 2.6-fold higher in HFD relative to RD mice. Exercise suppressed MAT in RD-E mice by more than half compared with RD. Running similarly inhibited MAT acquisition in HFD mice. Exercise significantly increased bone quantity in both diet groups. Thus, HFD caused significant accumulation of MAT; importantly running exercise limited MAT acquisition while promoting bone formation during both diets. That MAT is exquisitely responsive to diet and exercise, and its regulation by exercise appears to be inversely proportional to effects on exercise induced bone formation, is relevant for an aging and sedentary population. PMID:24709686

Aerobic Exercise Attenuates the Loss of Skeletal Muscle during Energy Restriction in Adults with Visceral Adiposity

PubMed Central

Yoshimura, Eiichi; Kumahara, Hideaki; Tobina, Takuro; Matsuda, Takuro; Watabe, Kiwa; Matono, Sakiko; Ayabe, Makoto; Kiyonaga, Akira; Anzai, Keizo; Higaki, Yasuki; Tanaka, Hiroaki

2014-01-01

Objective To evaluate the effects of energy restriction with or without aerobic exercise on thigh muscle mass and quality in adults with visceral adiposity. Methods 75 males and females were randomly assigned to the groups ‘diet only’ (DO; n = 42) or ‘diet plus aerobic exercise’ (D/Ex; n = 33) for 12 weeks. The target energy intake in both groups was 25 kcal/kg of ideal body weight. Subjects in the D/Ex group were instructed to exercise for ≥300 min/week at lactate threshold. Computed tomography was used to measure thigh muscle cross-sectional area (CSA), normal-density muscle area (NDMA), and visceral fat area. Results Total body weight (DO: −6.6 ± 3.6%; D/Ex: −7.3 ± 4.6%) and visceral fat (DO: −16.0 ± 13.8%; D/Ex: −23.1 ± 14.7%) decreased significantly in both groups; however, the changes were not significantly different between the two groups. The decrease in muscle CSA was significantly greater in the DO group (-5.1 ± 4.5%) compared with the D/Ex group (-2.5 ± 5.0%). NDMA decreased significantly in the DO (-4.9 ± 4.9%) but not in the D/Ex group (-1.4 ± 5.0%). Conclusion Aerobic exercise attenuated the loss of skeletal muscle during energy restriction in adults with visceral adiposity. PMID:24457527

High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity

PubMed Central

Denou, Emmanuel; Marcinko, Katarina; Surette, Michael G.; Steinberg, Gregory R.

2016-01-01

Diet and exercise underpin the risk of obesity-related metabolic disease. Diet alters the gut microbiota, which contributes to aspects of metabolic disease during obesity. Repeated exercise provides metabolic benefits during obesity. We assessed whether exercise could oppose changes in the taxonomic and predicted metagenomic characteristics of the gut microbiota during diet-induced obesity. We hypothesized that high-intensity interval training (HIIT) would counteract high-fat diet (HFD)-induced changes in the microbiota without altering obesity in mice. Compared with chow-fed mice, an obesity-causing HFD decreased the Bacteroidetes-to-Firmicutes ratio and decreased the genetic capacity in the fecal microbiota for metabolic pathways such as the tricarboxylic acid (TCA) cycle. After HFD-induced obesity was established, a subset of mice were HIIT for 6 wk, which increased host aerobic capacity but did not alter body or adipose tissue mass. The effects of exercise training on the microbiota were gut segment dependent and more extensive in the distal gut. HIIT increased the alpha diversity and Bacteroidetes/Firmicutes ratio of the distal gut and fecal microbiota during diet-induced obesity. Exercise training increased the predicted genetic capacity related to the TCA cycle among other aspects of metabolism. Strikingly, the same microbial metabolism indexes that were increased by exercise were all decreased in HFD-fed vs. chow diet-fed mice. Therefore, exercise training directly opposed some of the obesity-related changes in gut microbiota, including lower metagenomic indexes of metabolism. Some host and microbial pathways appeared similarly affected by exercise. These exercise- and diet-induced microbiota interactions can be captured in feces. PMID:27117007

High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity.

PubMed

Denou, Emmanuel; Marcinko, Katarina; Surette, Michael G; Steinberg, Gregory R; Schertzer, Jonathan D

2016-06-01

Diet and exercise underpin the risk of obesity-related metabolic disease. Diet alters the gut microbiota, which contributes to aspects of metabolic disease during obesity. Repeated exercise provides metabolic benefits during obesity. We assessed whether exercise could oppose changes in the taxonomic and predicted metagenomic characteristics of the gut microbiota during diet-induced obesity. We hypothesized that high-intensity interval training (HIIT) would counteract high-fat diet (HFD)-induced changes in the microbiota without altering obesity in mice. Compared with chow-fed mice, an obesity-causing HFD decreased the Bacteroidetes-to-Firmicutes ratio and decreased the genetic capacity in the fecal microbiota for metabolic pathways such as the tricarboxylic acid (TCA) cycle. After HFD-induced obesity was established, a subset of mice were HIIT for 6 wk, which increased host aerobic capacity but did not alter body or adipose tissue mass. The effects of exercise training on the microbiota were gut segment dependent and more extensive in the distal gut. HIIT increased the alpha diversity and Bacteroidetes/Firmicutes ratio of the distal gut and fecal microbiota during diet-induced obesity. Exercise training increased the predicted genetic capacity related to the TCA cycle among other aspects of metabolism. Strikingly, the same microbial metabolism indexes that were increased by exercise were all decreased in HFD-fed vs. chow diet-fed mice. Therefore, exercise training directly opposed some of the obesity-related changes in gut microbiota, including lower metagenomic indexes of metabolism. Some host and microbial pathways appeared similarly affected by exercise. These exercise- and diet-induced microbiota interactions can be captured in feces. Copyright © 2016 the American Physiological Society.

Plasma irisin levels progressively increase in response to increasing exercise workloads in young, healthy, active subjects.

PubMed

Daskalopoulou, Stella S; Cooke, Alexandra B; Gomez, Yessica-Haydee; Mutter, Andrew F; Filippaios, Andreas; Mesfum, Ertirea T; Mantzoros, Christos S

2014-09-01

Irisin, a recently discovered myokine, has been shown to induce browning of white adipose tissue, enhancing energy expenditure and mediating some of the beneficial effects of exercise. We aimed to estimate the time frame of changes in irisin levels after acute exercise and the effect of different exercise workloads and intensities on circulating irisin levels immediately post-exercise. In a pilot study, four healthy subjects (22.5±1.7 years) underwent maximal workload exercise (maximal oxygen consumption, VO2 max) and blood was drawn at prespecified intervals to define the time frame of pre- and post-exercise irisin changes over a 24-h period. In the main study, 35 healthy, non-smoking (23.0±3.3 years) men and women (n=20/15) underwent three exercise protocols ≥48-h apart, in random order: i) maximal workload (VO2 max); ii) relative workload (70% of VO2 max/10 min); and iii) absolute workload (75 W/10 min). Blood was drawn immediately pre-exercise and 3 min post-exercise. In the pilot study, irisin levels increased by 35% 3 min post-exercise, then dropped and remained relatively constant. In the main study, irisin levels post-exercise were significantly higher than those of pre-exercise after all workloads (all, P<0.001). Post-to-pre-exercise differences in irisin levels were significantly different between workloads (P=0.001), with the greatest increase by 34% following maximal workload (P=0.004 vs relative and absolute). Circulating irisin levels were acutely elevated in response to exercise, with a greater increase after maximal workload. These findings suggest that irisin release could be a function of muscle energy demand. Future studies need to determine the underlying mechanisms of irisin release and explore irisin's therapeutic potential. © 2014 European Society of Endocrinology.

The effect of a multidisciplinary intervention program on hepatic adiposity in overweight-obese children: protocol of the EFIGRO study.

PubMed

Medrano, M; Maiz, E; Maldonado-Martín, S; Arenaza, L; Rodríguez-Vigil, B; Ortega, F B; Ruiz, J R; Larrarte, E; Diez-López, I; Sarasúa-Miranda, A; Tobalina, I; Barrenechea, L; Pérez-Asenjo, J; Kannengiesser, S; Manhães-Savio, A; Echaniz, O; Labayen, I

2015-11-01

Non-alcoholic fatty liver disease is the most frequent liver abnormality observed in overweight or obese children and is strongly associated with metabolic syndrome and insulin resistance. (i) To evaluate the effect of a 22-week multidisciplinary intervention program on hepatic fat fraction in overweight or obese children and (ii) to examine the effect of the intervention on cardiometabolic risk factors, self-esteem and well-being. A total of 160 children, 9-11 years, will be recruited by pediatricians and randomly assigned to control (N = 80) or intervention (N = 80) groups. The control group will receive a family-based lifestyle and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week). The duration of training sessions will be 90 min of exercise, including warm-up, moderate to vigorous aerobic activities, and strength exercises. The primary outcome is the change in hepatic fat fraction (magnetic resonance imaging, MRI). Secondary outcomes include cardiometabolic risk factors such as total adiposity (dual Xray absorptiometry), visceral adiposity (MRI), functional peak aerobic capacity (cardiopulmonary exercise testing), blood pressure, muscular fitness, speed–agility, and fasting blood insulin, glucose, C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, lipid profile and psychological measurements (questionnaires). All the measurements will be evaluated at baseline prior to randomization and after the intervention. This study will provide insight in the efficacy of a multidisciplinary intervention program including healthy lifestyle education, psycho-education and supervised exercise to reduce hepatic fat and cardiometabolic risk in overweight children.

Relationship of adiposity to the population distribution of plasma triglyceride concentrations in vigorously active men and women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Paul T.

2002-12-21

Context and Objective: Vigorous exercise, alcohol and weight loss are all known to increase HDL-cholesterol, however, it is not known whether these interventions raise low HDL as effectively as has been demonstrated for normal HDL. Design: Physician-supplied medical data from 7,288 male and 2,359 female runners were divided into five strata according to their self-reported usual running distance, reported alcohol intake, body mass index (BMI) or waist circumference. Within each stratum, the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for HDL-cholesterol were then determined. Bootstrap resampling of least-squares regression was applied to determine the cross-sectional relationships between thesemore » factors and each percentile of the HDL-cholesterol distribution. Results: In both sexes, the rise in HDL-cholesterol per unit of vigorous exercise or alcohol intake was at least twice as great at the 95th percentile as at the 5th percentile of the HDL-distribution. There was also a significant graded increase in the slopes relating exercise (km run) and alcohol intake to HDL between the 5th and the 95th percentile. Men's HDL-cholesterol decreased in association with fatness (BMI and waist circumference) more sharply at the 95th than at the 5th percentile of the HDL-distribution. Conclusions: Although exercise, alcohol and adiposity were all related to HDL-cholesterol, the elevation in HDL per km run or ounce of alcohol consumed, and reduction in HDL per kg of body weight (men only), was least when HDL was low and greatest when HDL was high. These cross-sectional relationships support the hypothesis that men and women who have low HDL-cholesterol will be less responsive to exercise and alcohol (and weight loss in men) as compared to those who have high HDL-cholesterol.« less

A systematic review and meta-analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue.

PubMed

Verheggen, R J H M; Maessen, M F H; Green, D J; Hermus, A R M M; Hopman, M T E; Thijssen, D H T

2016-08-01

Exercise training ('exercise') and hypocaloric diet ('diet') are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta-analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P < 0.0001). When comparing diet versus training, diet caused a larger weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R(2)  = 0.737, P < 0.001), and a modest correlation after exercise (R(2)  = 0.451, P < 0.001). In the absence of weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle-interventions. © 2016 World Obesity.

Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer.

PubMed

Zahid, Heba; Simpson, Evan R; Brown, Kristy A

2016-12-01

Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat. The regulation of aromatase in the breast adipose stromal cell in response to inflammatory mediators is under the control of complex signaling pathways, including metabolic pathways involving LKB1/AMPK, p53, HIF1α and PKM2. Interventions aimed at modifying weight, including diet and exercise, are associated with changes in adipose tissue inflammation and estrogen production that are likely to impact breast cancer risk. This review will present an overview of these topics. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Positive effects of physical exercise on reducing the relationship between subcutaneous abdominal fat and morbility risk].

PubMed

González Calvo, G; Hernández Sánchez, S; Pozo Rosado, P; García López, D

2011-01-01

The consequences related to the accumulation of abdominal fat above healthy levels create a considerable organic damage. Among the physiological consequences we can highlight heart diseases, hypertension, type-2 diabetes, obesity and metabolic syndrome, which drastically reduce life expectancy and quality. Evidence shows that health improvement is correlated to greater levels of physical activity. However, physical exercise can create oxidative damage on organs and muscular tissue, more relevant in subjects with a high percentage of abdominal fat. This piece of work determines which are the fundamental variables of the exercise program in order to optimize its advantages while minimizing oxidative stress. To know the key variables in the accumulation of abdominal fat above healthy levels, and the role of exercise in prevention and improvement of such issue. SPECIFIC PURPOSES: 1) to identify the key variables in an exercise program aimed at reducing abdominal fat; 2) to understand the relationship between abdominal fat, health and exercise; 3) to review the latest research related to physical exercise and its effect on abdominal adipose tissue. A search and identification of original and reviewed articles will be carried out in indexed impact journals within the main databases. Regular physical exercise, most notably aerobic one, reduces body adipose tissue deposits in general, and abdominal ones in particular, both in obese and overweight subjects.

Pigment epithelium-derived factor, insulin sensitivity, and adiposity in polycystic ovary syndrome: impact of exercise training.

PubMed

Joham, Anju E; Teede, Helena J; Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Strauss, Boyd J; Paul, Eldho; Watt, Matthew J

2012-12-01

Pigment epithelium-derived factor (PEDF) is upregulated in obese rodents and is involved in the development of insulin resistance (IR). We aim to explore the relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular risk factors in obese women with polycystic ovary syndrome (PCOS) and weight-matched controls and to examine the impact of endurance exercise training on PEDF. This prospective cohort intervention study was based at a tertiary medical center. Twenty obese PCOS women and 14 non-PCOS weight-matched women were studied at baseline. PEDF, cardiometabolic markers, detailed body composition, and euglycemic-hyperinsulinemic clamps were performed and measures were repeated in 10 PCOS and 8 non-PCOS women following 12 weeks of intensified aerobic exercise. Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to controls (175.6 ± 96.3 and 257.2 ± 64.3 mg.m(-2).min(-1)) at baseline, yet both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR (r = -0.41, P = 0.03) and high-density lipoprotein (HDL) (r = -0.46, P = 0.01), and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P = 0.004). The correlation with GIR was not significant after adjusting for fat mass (P = 0.07). Exercise training maintained BMI and increased GIR in both groups; however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is not associated with IR when adjusted for fat mass, and is not reduced by endurance exercise training despite improved insulin sensitivity. PEDF was associated with cardiovascular risk factors, suggesting PEDF may be a marker of cardiovascular risk status.

Reduction in obesity and coronary risk factors after high caloric exercise training in overweight coronary patients.

PubMed

Savage, Patrick D; Brochu, Martin; Poehlman, Eric T; Ades, Philip A

2003-08-01

The majority of patients with coronary heart disease (CHD) are overweight. However, little weight loss occurs with participation in a standard cardiac rehabilitation (CR) program. Fifteen overweight patients (average body mass index of 31.0 kg/m2) with CHD completed a 4-month exercise training program in a CR program. The exercise program consisted primarily of walking long duration (60-90 minutes per session) 5 to 7 days per week at a relatively low intensity of 50% to 60% of peak VO2. Measures of body composition by dual-energy x-ray absorptiometry, body fat distribution by computed tomography, plasma lipid-lipoprotein, glucose and insulin concentrations, and peak VO2 were obtained before and after the exercise intervention. Patients maintained an isocaloric diet throughout the study. Patients had reductions in total body weight (-4.6 kg), fat mass (-3.6 kg), percent body fat (-2.9%), and waist circumference (-5.6 cm) (all P <.001) while maintaining fat-free mass. Subcutaneous adipose tissue was reduced by 12% (P <.001) and visceral adipose tissue was lowered by 14% (P <.001). There were favorable changes in the lipid-metabolic profile with reductions in triglyceride levels (-23.7%), total cholesterol/HDL-C ratio (-14.3%), and fasting insulin levels (-22.3%) (all P <.05). Peak VO2 increased by 21.2% (P <.001). The present pilot study results suggest that a high caloric training exercise training program in the CR setting may be effective in promoting weight loss and improving coronary risk factors in overweight coronary patients. Although additional research with randomized control patients is needed, this alternative to traditional CR may be considered to maximize weight loss as part of a secondary prevention program.

Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise.

PubMed

Covington, Jeffrey D; Tam, Charmaine S; Pasarica, Magdalena; Redman, Leanne M

2016-05-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r = -0.73, p = 0.03; and r = -0.82, p = 0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. Copyright © 2014 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.

PubMed

Vandanmagsar, Bolormaa; Youm, Yun-Hee; Ravussin, Anthony; Galgani, Jose E; Stadler, Krisztian; Mynatt, Randall L; Ravussin, Eric; Stephens, Jacqueline M; Dixit, Vishwa Deep

2011-02-01

The emergence of chronic inflammation during obesity in the absence of overt infection or well-defined autoimmune processes is a puzzling phenomenon. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated 'danger signals' leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) and IL-18 secretion. We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity. We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue. Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling. Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-γ (IFN-γ) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue. Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.

Chronic exercise preserves lean muscle mass in masters athletes.

PubMed

Wroblewski, Andrew P; Amati, Francesca; Smiley, Mark A; Goodpaster, Bret; Wright, Vonda

2011-09-01

Aging is commonly associated with a loss of muscle mass and strength, resulting in falls, functional decline, and the subjective feeling of weakness. Exercise modulates the morbidities of muscle aging. Most studies, however, have examined muscle-loss changes in sedentary aging adults. This leaves the question of whether the changes that are commonly associated with muscle aging reflect the true physiology of muscle aging or whether they reflect disuse atrophy. This study evaluated whether high levels of chronic exercise prevents the loss of lean muscle mass and strength experienced in sedentary aging adults. A cross-section of 40 high-level recreational athletes ("masters athletes") who were aged 40 to 81 years and trained 4 to 5 times per week underwent tests of health/activity, body composition, quadriceps peak torque (PT), and magnetic resonance imaging of bilateral quadriceps. Mid-thigh muscle area, quadriceps area (QA), subcutaneous adipose tissue, and intramuscular adipose tissue were quantified in magnetic resonance imaging using medical image processing, analysis, and visualization software. One-way analysis of variance was used to examine age group differences. Relationships were evaluated using Spearman correlations. Mid-thigh muscle area (P = 0.31) and lean mass (P = 0.15) did not increase with age and were significantly related to retention of mid-thigh muscle area (P < 0.0001). This occurred despite an increase in total body fat percentage (P = 0.003) with age. Mid-thigh muscle area (P = 0.12), QA (P = 0.17), and quadriceps PT did not decline with age. Specific strength (strength per QA) did not decline significantly with age (P = 0.06). As muscle area increased, PT increased significantly (P = 0.008). There was not a significant relationship between intramuscular adipose tissue (P = 0.71) or lean mass (P = 0.4) and PT. This study contradicts the common observation that muscle mass and strength decline as a function of aging alone. Instead, these declines may signal the effect of chronic disuse rather than muscle aging. Evaluation of masters athletes removes disuse as a confounding variable in the study of lower-extremity function and loss of lean muscle mass. This maintenance of muscle mass and strength may decrease or eliminate the falls, functional decline, and loss of independence that are commonly seen in aging adults.

Exercise induces autophagy in peripheral tissues and in the brain.

PubMed

He, Congcong; Sumpter, Rhea; Levine, Beth

2012-10-01

We recently identified physical exercise as a newly defined inducer of autophagy in vivo. Exercise induced autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue. To study the physiological role of exercise-induced autophagy, we generated mice with a knock-in nonphosphorylatable mutation in BCL2 (Thr69Ala, Ser70Ala and Ser84Ala) (BCL2 AAA) that are defective in exercise- and starvation-induced autophagy but not in basal autophagy. We found that BCL2 AAA mice could not run on a treadmill as long as wild-type mice, and did not undergo exercise-mediated increases in skeletal glucose muscle uptake. Unlike wild-type mice, the BCL2 AAA mice failed to reverse high-fat diet-induced glucose intolerance after 8 weeks of exercise training, possibly due to defects in signaling pathways that regulate muscle glucose uptake and metabolism during exercise. Together, these findings suggested a hitherto unknown important role of autophagy in mediating exercise-induced metabolic benefits. In the present addendum, we show that treadmill exercise also induces autophagy in the cerebral cortex of adult mice. This observation raises the intriguing question of whether autophagy may in part mediate the beneficial effects of exercise in neurodegeneration, adult neurogenesis and improved cognitive function.

High-intensity interval versus moderate-intensity continuous training: Superior metabolic benefits in diet-induced obesity mice.

PubMed

Wang, Ningning; Liu, Yang; Ma, Yanan; Wen, Deliang

2017-12-15

Exercise is beneficial in obesity, however, the debate about the value of high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MICT) has been long lasting. Therefore, here we have compared the possible beneficial effects of two different exercise training regimes in a mouse model of diet-induced obesity (DIO). Following 7wk. on high fat diet (HFD), ten-week-old male ICR mice (n=30) were assigned to HIIT, distance-matched MICT or remained sedentary for the next 8 constitutive weeks while maintaining the dietary treatments. Age-matched sedentary mice with standard diet were used as a control (n=10). Exercise was performed on a motorized treadmill for 5days a week. Both modes of exercise ameliorated adiposity and related metabolic dysfunction induced by HFD and sedentary lifestyle, while mice following HIIT exhibited significantly lower body weight, percentage of fat mass and smaller adipocyte size. HIIT was more favorable in preventing liver lipid accumulation by restoring mRNA levels of genes involved in hepatic lipogenesis (SREBP1, ACC1, FAS) and β-oxidation (PPARα, CPT1a, HAD). In addition, HIIT was more efficient in mitigating adipose tissue inflammation and insulin insensitivity, partly dependent on abrogating phosphorylation of JNK/IRS1 (Ser307) pathway. Moreover, only HIIT led to pronounced beige adipocyte recruitment in inguinal subcutaneous adipose tissue. We conclude that HIIT contribute a more favorable regulation of metabolic dysfunctions in DIO mice compared with MICT. Copyright © 2017 Elsevier Inc. All rights reserved.

TSHB mRNA is linked to cholesterol metabolism in adipose tissue.

PubMed

Moreno-Navarrete, José María; Moreno, María; Ortega, Francisco; Xifra, Gemma; Hong, Shangyu; Asara, John M; Serrano, José C E; Jové, Mariona; Pissios, Pavlos; Blüher, Matthias; Ricart, Wifredo; Portero-Otin, Manuel; Fernández-Real, José Manuel

2017-10-01

Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-β ( TSHB ) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined. The bidirectional relationship between cholesterol and TSHB were studied in isolated human adipocytes. TSHB mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total- and LDL-cholesterol, and with AT-specific cholesterol metabolism-associated lipids [arachidonoyl cholesteryl ester, C8-dihydroceramide, N -stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased TSHB mRNA in human AT, whereas excess cholesterol up-regulated TSHB mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased HMGCR mRNA levels in human adipocytes. In mice, subcutaneous AT Tshb expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of TSHB as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT.-Moreno-Navarrete, J. M., Moreno, M., Ortega, F., Xifra, G., Hong, S., Asara, J. M., Serrano, J. C. E., Jové, M., Pissios, P., Blüher, M., Ricart, W., Portero-Otin, M., Fernández-Real, J. M. TSHB mRNA is linked to cholesterol metabolism in adipose tissue. © FASEB.

Abdominal fat reducing outcome of exercise training: fat burning or hydrocarbon source redistribution?

PubMed

Kuo, Chia-Hua; Harris, M Brennan

2016-07-01

Fat burning, defined by fatty acid oxidation into carbon dioxide, is the most described hypothesis to explain the actual abdominal fat reducing outcome of exercise training. This hypothesis is strengthened by evidence of increased whole-body lipolysis during exercise. As a result, aerobic training is widely recommended for obesity management. This intuition raises several paradoxes: first, both aerobic and resistance exercise training do not actually elevate 24 h fat oxidation, according to data from chamber-based indirect calorimetry. Second, anaerobic high-intensity intermittent training produces greater abdominal fat reduction than continuous aerobic training at similar amounts of energy expenditure. Third, significant body fat reduction in athletes occurs when oxygen supply decreases to inhibit fat burning during altitude-induced hypoxia exposure at the same training volume. Lack of oxygen increases post-meal blood distribution to human skeletal muscle, suggesting that shifting the postprandial hydrocarbons towards skeletal muscle away from adipose tissue might be more important than fat burning in decreasing abdominal fat. Creating a negative energy balance in fat cells due to competition of skeletal muscle for circulating hydrocarbon sources may be a better model to explain the abdominal fat reducing outcome of exercise than the fat-burning model.

Quantifying the effect of adipose tissue in muscle oximetry by near infrared spectroscopy

PubMed Central

Nasseri, Nassim; Kleiser, Stefan; Ostojic, Daniel; Karen, Tanja; Wolf, Martin

2016-01-01

Change of muscle tissue oxygen saturation (StO2), due to exercise, measured by near infrared spectroscopy (NIRS) is known to be lower for subjects with higher adipose tissue thickness. This is most likely not physiological but caused by the superficial fat and adipose tissue. In this paper we assessed, in vitro, the influence of adipose tissue thickness on muscle StO2, measured by NIRS oximeters. We measured StO2 of a liquid phantom by 3 continuous wave (CW) oximeters (Sensmart Model X-100 Universal Oximetry System, INVOS 5100C, and OxyPrem v1.3), as well as a frequency-domain oximeter, OxiplexTS, through superficial layers with 4 different thicknesses. Later, we employed the results to calibrate OxyPrem v1.3 for adipose tissue thickness in-vivo. PMID:27895999

Exercise in the management of type 2 diabetes mellitus: what are the benefits and how does it work?

PubMed

Duclos, Martine; Virally, Marie-Laure; Dejager, Sylvie

2011-05-01

In this article, we examine the results from meta-analyses of studies that have focused on the effects of supervised exercise in patients with established type 2 diabetes mellitus. Exercise has been clearly demonstrated to have benefits on blood glucose control (average reduction of glycated hemoglobin, 0.6%) and cardiovascular risk factors. These benefits are observed independently of any change in body mass index and fat mass, and are also seen in older populations. Multiple mechanisms are involved, and the improved insulin-sensitizing effect of exercise training is not restricted to muscle but extends to hepatic and adipose tissue. However, while the benefits of exercise in type 2 diabetes management are undisputable, it is not as easy to draw correlations between clinical benefit and the amount of physical activity included in daily life. Recent studies have shown encouraging results with moderate increases in physical activity, which are feasible for most patients and are sufficient to induce sustained positive changes for 2 years. Thus, the benefits of structured and supervised exercise in patients with type 2 diabetes have been consistently demonstrated. Currently, the primary challenge is to determine how long-term increased physical activity can be durably implemented in a patient's daily life.

Eight weeks of a combination of high intensity interval training and conventional training reduce visceral adiposity and improve physical fitness: a group-based intervention.

PubMed

Giannaki, Christoforos D; Aphamis, George; Sakkis, Panikos; Hadjicharalambous, Marios

2016-04-01

High intensity interval training (HIIT) has been recently promoted as an effective, low volume and time-efficient training method for improving fitness and health related parameters. The aim of the current study was to examine the effect of a combination of a group-based HIIT and conventional gym training on physical fitness and body composition parameters in healthy adults. Thirty nine healthy adults volunteered to participate in this eight-week intervention study. Twenty three participants performed regular gym training 4 days a week (C group), whereas the remaining 16 participants engaged twice a week in HIIT and twice in regular gym training (HIIT-C group) as the other group. Total body fat and visceral adiposity levels were calculated using bioelectrical impedance analysis. Physical fitness parameters such as cardiorespiratory fitness, speed, lower limb explosiveness, flexibility and isometric arm strength were assessed through a battery of field tests. Both exercise programs were effective in reducing total body fat and visceral adiposity (P<0.05) and improving handgrip strength, sprint time, jumping ability and flexibility (P<0.05) whilst only the combination of HIIT and conventional training improved cardiorespiratory fitness levels (P<0.05). A between of group changes analysis revealed that HIIT-C resulted in significantly greater reduction in both abdominal girth and visceral adiposity compared with conventional training (P<0.05). Eight weeks of combined group-based HIIT and conventional training improve various physical fitness parameters and reduce both total and visceral fat levels. This type of training was also found to be superior compared with conventional exercise training alone in terms of reducing more visceral adiposity levels. Group-based HIIT may consider as a good methods for individuals who exercise in gyms and craving to acquire significant fitness benefits in relatively short period of time.

Exercise-induced hypertension in men with metabolic syndrome: anthropometric, metabolic, and hemodynamic features.

PubMed

Gaudreault, Valérie; Després, Jean-Pierre; Rhéaume, Caroline; Alméras, Natalie; Bergeron, Jean; Tremblay, Angelo; Poirier, Paul

2013-02-01

Metabolic syndrome is associated with increased cardiac morbidity. The aim of this study was to evaluate exercise-induced hypertension (EIH) in men with metabolic syndrome and to explore potential associations with anthropometric and metabolic variables. A total of 179 normotensive men with metabolic syndrome underwent a maximal symptom-limited treadmill test. Blood pressure was measured at 5-min rest prior to exercise testing (anticipatory blood pressure), at every 3 min during the exercise, and during the recovery period. EIH was defined as maximum systolic blood pressure (SBP) ≥220 mmHg and/or maximum diastolic blood pressure (DBP) ≥100 mmHg. Of the 179 men, 87 (47%) presented EIH. Resting blood pressure values at baseline were 127±10/83±6 mmHg in EIH and 119±9/80±6 mmHg (P=0.01 for both) in normal blood pressure responders to exercise. Anticipatory SBP and DPS were higher in the group with EIH (P=0.001). Subjects with EIH presented higher waist circumference (WC) (P<0.01), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) levels as well as insulin resistance (all P<0.05). Abdominal subcutaneous adipose tissue and total body fat mass were comparable between groups. Subjects with EIH had higher abdominal visceral adipose tissue (P<0.001). The best predictors of EIH were resting SBP and abdominal obesity. Each increment of 5 cm in WC was associated with an odds ratio of 1.30 (1.20-1.68) for EIH. About half of our subjects with metabolic syndrome showed EIH. These men are characterized by a worsened metabolic profile. Our data suggest that a treadmill exercise test may be helpful to identify a potentially higher risk metabolic syndrome subset of subjects.

Muscle irisin response to aerobic vs HIIT in overweight female adolescents.

PubMed

Archundia-Herrera, Carolina; Macias-Cervantes, Maciste; Ruiz-Muñoz, Bernardo; Vargas-Ortiz, Katya; Kornhauser, Carlos; Perez-Vazquez, Victoriano

2017-01-01

Exercise stimulates the production of fibronectin type III domain-containing protein 5 (FNDC5), which is cleaved to release a protein called irisin. This protein induces browning of white adipose tissue resulting in increased thermogenesis. Different studies have measured circulating irisin at baseline and in response to exercise among a wide variety of individuals; yet, regarding the effect of different exercise intensities in obese adolescent girls, limited insight is available. This study compares the effect of acute aerobic exercise of moderate intensity and high-intensity interval training (HIIT) on irisin levels in skeletal muscle and plasma of sedentary overweight or obese female adolescents. The aerobic group (n = 15) and HIIT group (n = 15) underwent anthropometric and metabolic measurements, electrocardiogram, peak oxygen uptake (VO 2peak ), and two vastus lateralis muscle biopsies before and after session of workout. The session of aerobic exercise included cycling at 65% of their peak heart rate (HRpeak) for 40 min. In the HIIT group, exercise included six bouts of 1 min at 85-95% HRpeak separated by 1 min of recovery. Irisin levels were evaluated in samples of skeletal muscle (western blot) and plasma (ELISA). The levels of expression of irisin in skeletal muscle increased significantly after a session of HIIT (p < 0.05), while aerobic exercise no affect irisin levels. No significant differences between the groups in plasma irisin levels were found. The increase in muscle irisin levels was observed only following HIIT session. No increases in plasma irisin concentration were observed.

Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice.

PubMed

Uddin, Golam M; Youngson, Neil A; Sinclair, David A; Morris, Margaret J

2016-01-01

Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD(+) levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD(+) only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

Endurance training blocks uncoupling protein 1 up-regulation in brown adipose tissue while increasing uncoupling protein 3 in the muscle tissue of rats fed with a high-sugar diet.

PubMed

de Queiroz, Karina Barbosa; Rodovalho, Gisele Vieira; Guimarães, Juliana Bohnen; de Lima, Daniel Carvalho; Coimbra, Cândido Celso; Evangelista, Elísio Alberto; Guerra-Sá, Renata

2012-09-01

The mitochondrial uncoupling proteins (UCPs) of interscapular brown adipose tissue (iBAT) and of muscles play important roles in energy balance. For instance, the expression of UCP1 and UCP3 are modulated by free fatty acid gradients induced by high-sugar diets and acute exercise that is dependent on sympathetic stimulation. However, the effects of endurance training in animals fed with high-sugar diets are unknown. This study aims to evaluate the long-term effects of diet and exercise on UCP1 and UCP3 levels and energy balance efficiency. Rats fed with standard or high-sugar (HSD) diets were simultaneously subjected to running training over an 8-week period. After the training period, the rats were decapitated, and the iBAT and gastrocnemius muscle tissues were removed for evaluation of the β₃-receptor, Ucp1, and Ucp3 mRNA and protein expression, which were analyzed by quantitative reverse transcriptase polymerase chain reaction and Western blot, respectively. Groups fed with an HSD displayed a higher adiposity index and iBAT weight (P < .05), whereas exhibited an up-regulation of Ucp1 mRNA and protein levels (P < .05). Training increased β₃-receptor mRNA in iBAT and reduced the Ucp3 mRNA in muscle tissues. In association with an HSD, training restored the increasing β₃-receptor mRNA and greatly up-regulated the levels of Ucp3 mRNA. Therefore, training blocked the HSD-induced up-regulation of UCP1 expression in iBAT, whereas it up-regulated the expression of Ucp3 mRNA in muscle. These results suggest that training enhances the relationship between Ucp1/Ucp3 mRNA levels, which could result in higher energy efficiency, but not when HSD-induced elevated sympathetic activity is maintained. Copyright © 2012. Published by Elsevier Inc.

Catecholamines and obesity: effects of exercise and training.

PubMed

Zouhal, Hassane; Lemoine-Morel, Sophie; Mathieu, Marie-Eve; Casazza, Gretchen A; Jabbour, Georges

2013-07-01

Excess body fat in obese individuals can affect the catecholamine response to various stimuli. Indeed, several studies report lower plasma catecholamine concentrations in obese subjects compared with nonobese subjects in response to submaximal or maximal exercise. This low catecholamine response reflects decreased sympathetic nervous system (SNS) activity. Although the relationship between the SNS and obesity is not well established, some authors have suggested that low SNS activity may contribute to the development of obesity. A decreased catecholamine response could affect α- and β-adrenoceptor sensitivity in adipose tissue, reducing lipolysis and increasing fat stores. Few studies have examined the effects of obesity on the plasma catecholamine response at rest and during exercise in adolescents. It is interesting to note that the effects of age, sex, and degree of obesity and the impact of very intense exercise on the catecholamine response have not yet been well examined. Moreover, the hormonal concentrations measured in the majority of obesity studies did not take into account plasma volume changes. This methodological factor can also undoubtedly influence plasma catecholamine results.

SMAD3 Negatively Regulates Serum Irisin and Skeletal Muscle FNDC5 and Peroxisome Proliferator-activated Receptor γ Coactivator 1-α (PGC-1α) during Exercise*

PubMed Central

Tiano, Joseph P.; Springer, Danielle A.; Rane, Sushil G.

2015-01-01

Beige adipose cells are a distinct and inducible type of thermogenic fat cell that express the mitochondrial uncoupling protein-1 and thus represent a powerful target for treating obesity. Mice lacking the TGF-β effector protein SMAD3 are protected against diet-induced obesity because of browning of their white adipose tissue (WAT), leading to increased whole body energy expenditure. However, the role SMAD3 plays in WAT browning is not clearly understood. Irisin is an exercise-induced skeletal muscle hormone that induces WAT browning similar to that observed in SMAD3-deficient mice. Together, these observations suggested that SMAD3 may negatively regulate irisin production and/or secretion from skeletal muscle. To address this question, we used wild-type and SMAD3 knock-out (Smad3−/−) mice subjected to an exercise regime and C2C12 myotubes treated with TGF-β, a TGF-β receptor 1 pharmacological inhibitor, adenovirus expressing constitutively active SMAD3, or siRNA against SMAD3. We find that in Smad3−/− mice, exercise increases serum irisin and skeletal muscle FNDC5 (irisin precursor) and its upstream activator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) to a greater extent than in wild-type mice. In C2C12 myotubes, TGF-β suppresses FNDC5 and PGC-1α mRNA and protein levels via SMAD3 and promotes SMAD3 binding to the FNDC5 and PGC-1α promoters. These data establish that SMAD3 suppresses FNDC5 and PGC-1α in skeletal muscle cells. These findings shed light on the poorly understood regulation of irisin/FNDC5 by demonstrating a novel association between irisin and SMAD3 signaling in skeletal muscle. PMID:25648888

Red grape leaf extract improves endurance capacity by facilitating fatty acid utilization in skeletal muscle in mice.

PubMed

Minegishi, Yoshihiko; Haramizu, Satoshi; Hase, Tadashi; Murase, Takatoshi

2011-09-01

Improving endurance capacity leads to increased athletic performance and active lifestyles. The aim of this study was to investigate the effect of the intake of red grape leaf extract (RGLE), used as a traditional herbal medicine in the Mediterranean area, on endurance capacity in mice. Male BALB/c mice were divided into three experimental groups with similar swimming times and body weights; control group, 0.2% (w/w) and 0.5% RGLE group. Swimming times were measured for evaluation of endurance capacity once a week during the 10-week experimental period. Blood and tissues were collected from anesthetized mice immediately after 30 min of swimming exercise, and analyzed blood component and fatty acid oxidation enzyme activity, and gene expression in soleus muscle and mesenteric adipose tissue. Endurance capacity was improved by RGLE in a dose-related manner, and was significantly longer in the 0.5% RGLE group than in the control group at week 10. Plasma lactate levels after exercise in the 0.5% RGLE group were significantly lower than that in the control group. RGLE induced the upregulation of hormone-sensitive lipase mRNA in mesenteric adipose tissue, increased the plasma free fatty acid concentration after exercise, and enhanced fatty acid oxidation enzyme activity in the soleus muscle. Furthermore, peroxisome proliferator-activated receptor-gamma coactivator 1α (Pgc1α) and its downstream target genes were also significantly upregulated in the soleus muscle in the 0.5% RGLE group. Intake of RGLE upregulated Pgc1α expression and facilitated fatty acid oxidation in skeletal muscle, and these effects contributed, in part, to improve endurance capacity.

Effects of endurance exercise training on inflammatory circulating progenitor cell content in lean and obese adults.

PubMed

Niemiro, Grace M; Allen, Jacob M; Mailing, Lucy J; Khan, Naiman A; Holscher, Hannah D; Woods, Jeffrey A; De Lisio, Michael

2018-06-19

Chronic inflammation underlies many of the health decrements associated with obesity. Circulating progenitor cells can sense and respond to inflammatory stimuli, increasing the local inflammatory response within tissues. Here we show that 6 weeks of endurance exercise training significantly decreases inflammatory circulating progenitor cells in obese adults. These findings provide novel cellular mechanisms for the beneficial effects of exercise in obese adults. Circulating progenitor cells (CPCs) and subpopulations are normally found in the bone marrow, but can migrate to peripheral tissues to participate in local inflammation and/or remodelling. The purpose of this study was to compare the CPC response, particularly the inflammatory-primed haematopoietic stem and progenitor (HSPC) subpopulation, to a 6 week endurance exercise training (EET) intervention between lean and obese adults. Seventeen healthy weight (age: 23.9 ± 5.4 years, body mass index (BMI): 22.0 ± 2.6 kg m -2 ) and 10 obese (age: 29.0 ± 8.0 years, BMI: 33.1 ± 6.0 kg m -2 ) previously sedentary adults participated in an EET. Blood was collected before and after EET for quantification of CPCs and subpopulations via flow cytometry, colony forming unit assays and plasma concentrations of C-X-C motif chemokine 12 (CXCL12), granulocyte-colony stimulating factor (G-CSF), and chemokine (C-C motif) ligand 2 (CCL2). Exercise training reduced the number of circulating HSPCs and adipose tissue-derived mesenchymal stem cells (AT-MSCs). EET increased the colony forming potential of granulocytes and macrophages irrespective of BMI. EET reduced the number of HSPCs expressing the chemokine receptor CCR2 and the pro-inflammatory marker TLR4. EET-induced changes in adipose tissue-derived MSCs and bone marrow-derived MSCs were negatively related to changes in absolute fitness. Our results indicate that EET, regardless of BMI status, decreases CPCs and subpopulations, particularly those primed for contribution to tissue inflammation. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

PubMed

Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

2017-10-24

Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

Behavior change

USDA-ARS?s Scientific Manuscript database

This brief entry presents the mediating-moderating variable model as a conceptual framework for understanding behavior change in regard to physical activity/exercise and adiposity. The ideas are applied to real world situations....

A randomised placebo-exercise controlled trial of Kung Fu training for improvements in body composition in overweight/obese adolescents: the “Martial Fitness” study

PubMed Central

Tsang, Tracey W.; Kohn, Michael; Chow, Chin Moi; Singh, M Fiatarone

2009-01-01

The purpose of the study was to investigate if Chinese martial arts (Kung Fu, KF) might be effective for improving body composition, as well as being an appealing form of physical activity for inexperienced, sedentary, overweight/obese adolescents. Twenty subjects (age: 13.3 ± 1.8 y; BMI percentile: 98.6(86.5 - 99.8); 60% girls) were randomly-assigned to the supervised KF or placebo (Tai Chi, TC) control group 3 d.wk-1 for 6 months. We assessed body composition, including total and regional fat and lean mass, total and regional bone mineral density (BMD), percent lean and fat mass, body mass index and waist circumference, at baseline and after 6 months of training using anthropometry and dual-energy X-ray absorptiometry (DXA). Habitual physical activity and dietary intake were recorded as covariates via self-report at each time-point. As expected due to natural growth, significant increases in height, weight, total and lumbar BMD, and lean mass were seen in the cohort over time, with a trend for increased whole body fat mass, with no difference between groups. By contrast, percent fat and android fat mass via DXA did not increase in either group over time. The absence of a similar expected increase in central adiposity over 6 months could indicate a positive effect of participation in both programs on the metabolically critical abdominal adiposity in this cohort. Further research in this area is warranted to determine ways to increase uptake and compliance, and to see if longer-term martial arts training not only maintains, but improves abdominal fat mass and related metabolic health indices in overweight/ obese adolescents. Key points Participation in our martial arts trial attenuated the increases in body fat mass expected due to growth in our overweight/obese adolescent group. All subjects allocated to the Kung Fu intervention were satisfied with their Kung Fu training, in contrast to our placebo-exercise (Tai Chi) subjects, suggesting that this form of exercise is worth investigating further for adherence and efficacy. This was the first randomized, placebo-exercise controlled trial to be conducted, examining the effects of martial arts training alone on body composition in sedentary overweight/obese adolescents. Larger, longer-term trials are required to confirm our findings. PMID:24150562

[Microcirculatory investigations in hemophilia patients].

PubMed

Davydkin, I L; Kosiakova, Iu A

2012-01-01

to evaluate microcirculation (MC) and its influencing factors in hemophilia patients. In 44 hemophilia patients with recurrent hemarthrosis, laser Doppler flowmetry was used to evaluate resting MC above the index fingers, knee and ankle joints during an occlusion test, with allowance made for muscle and adipose tissue mass. The increased perfusion value above the afflicted joints was found to correspond to the phase of an exacerbation of posthemorrhagic inflammation and to be a risk factor of recurrent hemarrthrosis. Analysis of the occlusion test above the knee joints and index fingers revealed a diminished MC reserve and a tendency to precapillary spasm. MC changes were more pronounced in a shortage of muscle and adipose tissue mass. Hemophilia patients must regularly do physical exercises to make skeletal muscles develop well in order to prevent an exacerbation of the joint inflammatory process.

Physical exercise introduced after weaning enhances pancreatic islet responsiveness to glucose and potentiating agents in adult MSG-obese rats.

PubMed

Ribeiro, R A; Bonfleur, M L; Vanzela, E C; Zotti, A I; Scomparin, D X; Boschero, A C; Balbo, S L

2014-08-01

Physical exercise represents an alternative way to prevent and/or ameliorate chronic metabolic diseases. Disruption of sympathetic nervous system (SNS) activity contributes to adiposity in obese subjects. Here, we verified the preventive effect of swimming training upon adiposity, adrenal catecholamine storage, and pancreatic islet function in obese monosodium glutamate (MSG)-treated rats. Male neonatal Wistar rats received MSG (4 mg/g body weight) during the first 5 days of life and, at weaning, half of the rats were submitted to swimming training, 30 min/day, 3 days a week, until 90 days of age (exercised rats: MSGex). Half of the rats were used as controls (sedentary group, MSGsd). Exercise training (ET) decreased insulinemia and fat deposition in MSGex, and increased adrenal catecholamine content, compared with MSGsd rats. Insulinemia during the ivGTT was lower in MSGex rats, despite a lack of difference in glycemia. Swimming training enhanced insulin release in islets challenged by 2.8-8.3 mmol/l glucose, whereas, at supraphysiological glucose concentrations (11.1-16.7 mmol/l), MSGex islets secreted less insulin than MSGsd. No differences in insulin secretion were observed following l-arginine (Arg) or K(+) stimuli. In contrast, islets from MSGex rats secreted more insulin when exposed to carbachol (100 μmol/l), forskolin (10 μmol/l), or IBMX (1 mmol/l) at 8.3 mmol/l glucose. Additionally, MSGex islets presented a better epinephrine inhibition upon insulin release. These results demonstrate that ET prevented the onset of obesity in MSG rats, probably by enhancing adrenal catecholamine levels. ET ameliorates islet responsiveness to several compounds, as well as insulin peripheral action. © Georg Thieme Verlag KG Stuttgart · New York.

Adaptations of the aging animal to exercise: role of daily supplementation with melatonin.

PubMed

Mendes, Caroline; Lopes, Ana Maria de Souza; do Amaral, Fernanda Gaspar; Peliciari-Garcia, Rodrigo A; Turati, Ariane de Oliveira; Hirabara, Sandro M; Scialfa Falcão, Julieta H; Cipolla-Neto, José

2013-10-01

The pineal gland, through melatonin, seems to be of fundamental importance in determining the metabolic adaptations of adipose and muscle tissues to physical training. Evidence shows that pinealectomized animals fail to develop adaptive metabolic changes in response to aerobic exercise and therefore do not exhibit the same performance as control-trained animals. The known prominent reduction in melatonin synthesis in aging animals led us to investigate the metabolic adaptations to physical training in aged animals with and without daily melatonin replacement. Male Wistar rats were assigned to four groups: sedentary control (SC), trained control (TC), sedentary treated with melatonin (SM), and trained treated with melatonin (TM). Melatonin supplementation lasted 16 wk, and the animals were subjected to exercise during the last 8 wk of the experiment. After euthanasia, samples of liver, muscle, and adipose tissues were collected for analysis. Trained animals treated with melatonin presented better results in the following parameters: glucose tolerance, physical capacity, citrate synthase activity, hepatic and muscular glycogen content, body weight, protein expression of phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and protein kinase activated by adenosine monophosphate (AMPK) in the liver, as well as the protein expression of the glucose transporter type 4 (GLUT4) and AMPK in the muscle. In conclusion, these results demonstrate that melatonin supplementation in aging animals is of great importance for the required metabolic adaptations induced by aerobic exercise. Adequate levels of circulating melatonin are, therefore, necessary to improve energetic metabolism efficiency, reducing body weight and increasing insulin sensitivity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rare adipose disorders (RADs) masquerading as obesity

PubMed Central

Herbst, Karen L

2012-01-01

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations. PMID:22301856

An Online Guided E-Journal Exercise in Pre-Clerkship Years: Oxidative Phosphorylation in Brown Adipose Tissue

ERIC Educational Resources Information Center

Abali, Emine Ercikan; Phadtare, Sangita; Galt, Jim; Brodsky, Barbara

2014-01-01

The rationale for this mandatory, guided online e-journal exercise is to foster the ability of students to independently read medical and scientific literature in a critical manner and to integrate journal reading with their basic science knowledge. After a lecture on oxidative phosphorylation, students were assigned to read an article on brown…

Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

PubMed

Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

2016-08-01

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. Copyright © 2016 the American Physiological Society.

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice

PubMed Central

Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-01-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day−1). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training. PMID:22674717

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

PubMed

Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-09-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

Effect of High-Intensity Interval Training on Fitness, Fat Mass and Cardiometabolic Biomarkers in Children with Obesity: A Randomised Controlled Trial.

PubMed

Dias, Katrin A; Ingul, Charlotte B; Tjønna, Arnt E; Keating, Shelley E; Gomersall, Sjaan R; Follestad, Turid; Hosseini, Mansoureh S; Hollekim-Strand, Siri M; Ro, Torstein B; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Coombes, Jeff S

2018-03-01

Paediatric obesity significantly increases the risk of developing cardiometabolic diseases across the lifespan. Increasing cardiorespiratory fitness (CRF) could mitigate this risk. High-intensity interval training (HIIT) improves CRF in clinical adult populations but the evidence in paediatric obesity is inconsistent. The objectives of this study were to determine the efficacy of a 12-week, HIIT intervention for increasing CRF and reducing adiposity in children with obesity. Children with obesity (n = 99, 7-16 years old) were randomised into a 12-week intervention as follows: (1) HIIT [n = 33, 4 × 4-min bouts at 85-95% maximum heart rate (HR max ), interspersed with 3 min of active recovery at 50-70% HR max , 3 times/week] and nutrition advice; (2) moderate-intensity continuous training (MICT) [n = 32, 44 min at 60-70% HR max , 3 times/week] and nutrition advice; and (3) nutrition advice only (nutrition) [n = 34]. CRF was quantified through a maximal exercise test ([Formula: see text]) while adiposity was assessed using magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and air-displacement plethysmography. HIIT stimulated significant increases in relative [Formula: see text] compared with MICT (+3.6 mL/kg/min, 95% CI 1.1-6.0, P = 0.004) and the nutrition intervention (+5.4 mL/kg/min, 95% CI 2.9-7.9, P = 0.001). However, the intervention had no significant effect on visceral and subcutaneous adipose tissue, whole body composition or cardiometabolic biomarkers (P > 0.05). A 12-week, HIIT intervention was highly effective in increasing cardiorespiratory fitness when compared with MICT and nutrition interventions. While there were no concomitant reductions in adiposity or blood biomarkers, the cardiometabolic health benefit conferred through increased CRF should be noted. Clinicaltrials.gov; NCT01991106.

Endurance exercise and selective breeding for longevity extend Drosophila healthspan by overlapping mechanisms.

PubMed

Sujkowski, Alyson; Bazzell, Brian; Carpenter, Kylie; Arking, Robert; Wessells, Robert J

2015-08-01

Endurance exercise has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. In addition, long-term exercise reduces the incidence of age-related diseases in humans and in model organisms. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare gene expression changes during endurance training in Drosophila melanogaster to gene expression changes during selective breeding for longevity. Microarrays indicate that 65% of gene expression changes found in flies selectively bred for longevity are also found in flies subjected to three weeks of exercise training. We find that both selective breeding and endurance training increase endurance, cardiac performance, running speed, flying height, and levels of autophagy in adipose tissue. Both interventions generally upregulate stress defense, folate metabolism, and lipase activity, while downregulating carbohydrate metabolism and odorant receptor expression. Several members of the methuselah-like (mthl) gene family are downregulated by both interventions. Knockdown of mthl-3 was sufficient to provide extension of negative geotaxis behavior, endurance and cardiac stress resistance. These results provide support for endurance exercise as a broadly acting anti-aging intervention and confirm that exercise training acts in part by targeting longevity assurance pathways.

Effects of fasted vs fed-state exercise on performance and post-exercise metabolism: A systematic review and meta-analysis.

PubMed

Aird, T P; Davies, R W; Carson, B P

2018-05-01

The effects of nutrition on exercise metabolism and performance remain an important topic among sports scientists, clinical, and athletic populations. Recently, fasted exercise has garnered interest as a beneficial stimulus which induces superior metabolic adaptations to fed exercise in key peripheral tissues. Conversely, pre-exercise feeding augments exercise performance compared with fasting conditions. Given these seemingly divergent effects on performance and metabolism, an appraisal of the literature is warranted. This review determined the effects of fasting vs pre-exercise feeding on continuous aerobic and anaerobic or intermittent exercise performance, and post-exercise metabolic adaptations. A search was performed using the MEDLINE and PubMed search engines. The literature search identified 46 studies meeting the relevant inclusion criteria. The Delphi list was used to assess study quality. A meta-analysis and meta-regression were performed where appropriate. Findings indicated that pre-exercise feeding enhanced prolonged (P = .012), but not shorter duration aerobic exercise performance (P = .687). Fasted exercise increased post-exercise circulating FFAs (P = .023) compared to fed exercise. It is evidenced that pre-exercise feeding blunted signaling in skeletal muscle and adipose tissue implicated in regulating components of metabolism, including mitochondrial adaptation and substrate utilization. This review's findings support the hypothesis that the fasted and fed conditions can divergently influence exercise metabolism and performance. Pre-exercise feeding bolsters prolonged aerobic performance, while seminal evidence highlights potential beneficial metabolic adaptations that fasted exercise may induce in peripheral tissues. However, further research is required to fully elucidate the acute and chronic physiological adaptations to fasted vs fed exercise. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Browning of subcutaneous fat and higher surface temperature in response to phenotype selection for advanced endurance exercise performance in male DUhTP mice.

PubMed

Brenmoehl, J; Ohde, D; Albrecht, E; Walz, C; Tuchscherer, A; Hoeflich, A

2017-02-01

For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice. Analysis of peripheral fat pads revealed increased brite (brown-in-white) subcutaneous adipose tissues and in subcutaneous fat from DUhTP mice higher levels of irisin and different markers of fat cell browning like T-box transcription factor (Tbx1), PPARα, and uncoupling protein (UCP1) (P < 0.05) when compared to unselected controls. UCP1 was further increased in subcutaneous fat from DUhTP mice in response to mild exercise (fourfold, P < 0.05). In addition, surface temperature of DUhTP mice was increased when compared to controls indicating a physiological effect of increased UCP1 expression. The present study suggests that DUhTP mice exhibit different markers of mitochondrial biogenesis and fat browning without external stimuli. At an age of 43 days, sedentary DUhTP mice have improved metabolic health as judged from lower levels of blood glucose after an oral glucose tolerance test. Consequently, the non-inbred mouse model DUhTP represents a novel model for the identification of fat cell browning mechanisms in white adipose tissues.

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels

PubMed Central

Abbenhardt, Clare; McTiernan, Anne; Alfano, Catherine M.; Wener, Mark H.; Campbell, Kristin L.; Duggan, Catherine; Foster-Schubert, Karen E.; Kong, Angela; Toriola, Adetunji T; Potter, John D.; Mason, Caitlin; Xiao, Liren; Blackburn, George L.; Bain, Carolyn; Ulrich, Cornelia M.

2013-01-01

Background Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes, and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Methods Overweight/obese postmenopausal women (n=439) were randomized as follows: 1) a reduced calorie, weight loss diet (diet; N=118); 2) moderate-to-vigorous intensity aerobic exercise (exercise; N=117); 3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117); or 4) control (N=87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Results Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet+exercise group (both p≤0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, −40.1%, p<0.0001; diet, −27.1%, p<0.0001; exercise, −12.7%, p=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, p-trend=0.0002; diet+exercise, p-trend=0.0005) and directly associated with leptin (diet, p-trend<0.0001; diet+exercise, p-trend<0.0001). Conclusion Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. PMID:23432360

Obesity, Asthma, and Exercise in Child and Adolescent Health

PubMed Central

Lu, Kim D.; Manoukian, Krikor; Radom-Aizik, Shlomit; Cooper, Dan M.; Galant, Stanley P.

2018-01-01

Obesity increases the risk of asthma throughout life but the underlying mechanisms linking these all too common threats to child health are poorly understood. Acute bouts of exercise, aerobic fitness, and levels of physical activity clearly play a role in the pathogenesis and/or management of both childhood obesity and asthma. Moreover, both obesity and physical inactivity are associated with asthma symptomatology and response to therapy (a particularly challenging feature of obesity-related asthma). In this article, we review current understandings of the link between physical activity, aerobic fitness and the asthma-obesity link in children and adolescents (e.g., the impact of chronic low-grade inflammation, lung mechanics, and direct effects of metabolic health on the lung). Gaps in our knowledge regarding the physiological mechanisms linking asthma, obesity and exercise are often compounded by imprecise estimations of adiposity and challenges of assessing aerobic fitness in children. Addressing these gaps could lead to practical interventions and clinical approaches that could mitigate the profound health care crisis of the increasing comorbidity of asthma, physical inactivity, and obesity in children. PMID:26618409

Reduction in trunk fat predicts cardiovascular exercise training-related reductions in C-reactive protein.

PubMed

Vieira, V J; Hu, L; Valentine, R J; McAuley, E; Evans, E M; Baynard, T; Woods, J A

2009-05-01

C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. We sought to determine (1) if 10 months of cardiovascular exercise training (Cardio) reduces CRP in a group of older adults, (2) if such a reduction is related to improvements in trunk fat, fitness, and/or psychosocial variables, and (3) if the effect of Cardio on CRP differs between men and women. Community-dwelling residents (n=127; 60-83 yrs) were randomized to a Flex group (n=61) where they participated in 2-75 min supervised sessions per wk during which they performed non-cardiovascular flexibility and balance exercises or a Cardio group (n=66) where they participated in three supervised sessions per wk during which they performed cardiovascular exercises for approximately 45-60 min at 60-70% maximal oxygen uptake. The main outcome measures were serum CRP, cardiovascular fitness, total and central adiposity, and self-reported psychosocial function. Cardio experienced a reduction in CRP (-0.5mg/L), as well as improvements in fitness (+7%) and total (-1.5%) and central (i.e., trunk) (-2.5%) adiposity. These relationships were not modified by sex. Regression analyses indicated that only the reduction in trunk fat was significantly related to the reduction in CRP. Ten months of cardiovascular exercise training reduced CRP in previously sedentary older adults and this effect was partially mediated by a reduction in trunk fat.

Why even active people get fatter--the asymmetric effects ofincreasing and decreasing exercise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Paul T.

2006-01-06

Background: Public health policies for preventing obesityneed guidelines for active individuals who are at risk due to exerciserecidivism. Methods: Changes in adiposity were compared to the runningdistances at baseline and follow-up in men and women whose reportedexercise increased (N=4,632 and 1,953, respectively) or decreased (17,280and 5,970, respectively) during 7.7 years of follow-up. Results: PerDelta km/wk, decreases in running distance caused over four-fold greaterweight gain between 0-8 km/wk (slope+-SE, males: -0.068+ -0.005 kg/m2,females: -0.080+-0.01 kg/m2) than between 32-48 km/wk (-0.017+-0.002 and-0.010+-0.005 kg/m2, respectively). In contrast, increases in runningdistance produced the smallest weight losses between 0-8 km/wk andstatistically significant weight loss onlymore » above 16 km/wk in males and 32km/wk in females. Above 32 km/wk (30 kcal/kg) in men and 16 km/wk (15kcal/kg) in women, weight loss from increasing exercise was equal to orgreater than weight gained with decreasing exercise, otherwise weightgain exceeded weight loss. Substantial weight gain occurred in runnerswho quit running, which would be mostly retained with resumed activity.Conclusion: Public health recommendations should warn against the risksof irreversible weight gain with exercise cessation. Weight gained due toreductions in exercise below 30 kcal/kg in men and 15 kcal/kg in womenmay not be reversed by resuming prior activity. Current IOM guidelines(i.e., maintain total energy expenditure at 160 percent of basal) agreewith the men s exercise threshold for symmetric weight change withchanging exercise levels.« less

Reduced cortical BACE1 content with one bout of exercise is accompanied by declines in AMPK, Akt, and MAPK signaling in obese, glucose-intolerant mice

PubMed Central

Baumeister, P.; Peppler, W. T.; Wright, D. C.; Little, J. P.

2015-01-01

Obesity and type 2 diabetes are significant risk factors in the development of neurodegenerative diseases, such as Alzheimer's disease. A variety of cellular mechanisms, such as altered Akt and AMPK and increased inflammatory signaling, contribute to neurodegeneration. Exercise training can improve markers of neurodegeneration, but the underlying mechanisms remain unknown. The purpose of this study was to determine the effects of a single bout of exercise on markers of neurodegeneration and inflammation in brains from mice fed a high-fat diet. Male C57BL/6 mice were fed a low (LFD; 10% kcal from lard)- or a high-fat diet (HFD; 60% kcal from lard) for 7 wk. HFD mice underwent an acute bout of exercise (treadmill running: 15 m/min, 5% incline, 120 min) followed by a recovery period of 2 h. The HFD increased body mass and glucose intolerance (both P < 0.05). This was accompanied by an approximately twofold increase in the phosphorylation of Akt, ERK, and GSK in the cortex (P < 0.05). Following exercise, there was a decrease in beta-site amyloid precursor protein cleaving enzyme 1 (BACE1; P < 0.05) and activity (P < 0.001). This was accompanied by a reduction in AMPK phosphorylation, indicative of a decline in cellular stress (P < 0.05). Akt and ERK phosphorylation were decreased following exercise in HFD mice to a level similar to that of the LFD mice (P < 0.05). This study demonstrates that a single bout of exercise can reduce BACE1 content and activity independent of changes in adiposity. This effect is associated with reductions in Akt, ERK, and AMPK signaling in the cortex. PMID:26404616

Comparison of the effects of swimming and Tai Chi Chuan on body fat composition in elderly people.

PubMed

Yu, Tung-Yang; Pei, Yu-Cheng; Lau, Yiu-Chung; Chen, Chih-Kuang; Hsu, Hung-Chih; Wong, Alice M K

2007-01-01

Accumulation of fat and substantial loss of muscle mass are common phenomena in the elderly. In this study, we observed the effects of Tai Chi Chuan (TCC) and swimming, two exercises suitable for elderly people, on the percentage body fat and fat distribution by measuring subcutaneous adipose tissue thickness and body composition. Subjects were divided into three groups: regular swimmers (n = 20), regular TCC practitioners (n = 32), and age-matched control subjects (n = 31). Subcutaneous adipose tissue thickness was taken using a Lange skinfold caliper at the chests, abdomens, and thighs in the men, and the triceps, suprailium, and thighs in the women. Mid-arm circumference (MAC) was measured on the non-dominant upper arm using fiberglass tape. Body composition was analyzed using the Inbody 3.0 logo, a bioelectrical impedance analysis (BIA) system. No significant differences were found between the three test groups in relation to total body adiposity and arm muscle circumference in the men and women. There was significantly less subcutaneous adipose tissue at the abdomen (p = 0.011) and thigh (p < 0.001) of TCC-group men and at the thighs (p < 0.001) of the swimming group compared with the control group. In women, only the thigh skinfold (p = 0.002) showed a decrease in the TCC group compared with the control group. Swimming and TCC may not decrease total fat adiposity in elderly men and women, however, they may change body fat distribution due to certain muscle group usage. The differences observed in the effects of exercise on body fat distribution between elderly women and men may be gender-related.

Aerobic exercise training performed by parents reduces mice offspring adiposity.

PubMed

Romero, Paulo Vitor da Silva; Guariglia, Débora Alves; Da Rocha, Francielli Ferreira; Picoli, Caroline de Carvalho; Gilio, Gustavo Renan; Fabricio, Gabriel Sergio; Mathias, Paulo Cesar de Freitas; Moraes, Solange Marta Franzói de; Peres, Sidney Barnabé

2018-07-01

The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

Autonomic function responses to training: Correlation with body composition changes.

PubMed

Tian, Ye; Huang, Chuanye; He, Zihong; Hong, Ping; Zhao, Jiexiu

2015-11-01

The causal relation between autonomic function and adiposity is an unresolved issue. Thus, we studied whether resting heart rate variability (HRV) changes could be used to predict changes in body composition after 16 weeks of individualized exercise training. A total of 117 sedentary overweight/obese adults volunteered to join an intervention group (IN, n=82) or a control group (CON, n=35). The intervention group trained for 30-40 min three times a week with an intensity of 85-100% of individual ventilatory threshold (Thvent). At baseline and after a 16-week training period, resting HRV variables, body composition and peak oxygen uptake (VO2peak) were assessed. Compared with CON, exercise training significantly improved HRV and body composition and increased VO2peak (P<0.05). Significant correlations were observed between changes of HRV variables and body composition indices and VO2peak (P<0.05). Greater individual changes in HRV in response to exercise training were observed for those with greater total and central fat loss. Individual aerobic-based exercise training was for improving autonomic function and resting HRV responses to aerobic training is a potential indicator for adaptations to exercise training. Copyright © 2015. Published by Elsevier Inc.

AMPK and the biochemistry of exercise: Implications for human health and disease

PubMed Central

Richter, Erik A.; Ruderman, Neil B.

2009-01-01

Synopsis AMP-activated protein kinase (AMPK) is a phylogenetically conserved fuel-sensing enzyme that is present in all mammalian cells. During exercise, it is activated in skeletal muscle in humans, and at least in rodents, also in adipose tissue, liver and perhaps other organs by events that increase the AMP/ATP ratio. When activated AMPK stimulates energy generating processes such as glucose uptake and fatty acid oxidation and decreases energy consuming processes such as protein and lipid synthesis. Exercise is perhaps the most powerful physiological activator of AMPK and a unique model for studying its many physiological roles. In addition, it improves the metabolic status of rodents with a metabolic syndrome phenotype, as does treatment with AMPK activating agents; therefore, it is tempting to attribute the therapeutic benefits of regular physical activity to activation of AMPK. Here we review the acute and chronic effects of exercise on AMPK activity in skeletal muscle and other tissues. We also discuss the potential role of AMPK activation in mediating the prevention and treatment by exercise of specific disorders associated with the metabolic syndrome including type 2 diabetes and Alzheimer’s disease. PMID:19196246

Reduction of O2 slow component by priming exercise: novel mechanistic insights from time-resolved near-infrared spectroscopy

PubMed Central

Fukuoka, Yoshiyuki; Poole, David C; Barstow, Thomas J; Kondo, Narihiko; Nishiwaki, Masato; Okushima, Dai; Koga, Shunsaku

2015-01-01

Novel time-resolved near-infrared spectroscopy (TR-NIRS), with adipose tissue thickness correction, was used to test the hypotheses that heavy priming exercise reduces the V̇O2 slow component (V̇O2SC) (1) by elevating microvascular [Hb] volume at multiple sites within the quadriceps femoris (2) rather than reducing the heterogeneity of muscle deoxygenation kinetics. Twelve subjects completed two 6-min bouts of heavy work rate exercise, separated by 6 min of unloaded cycling. Priming exercise induced faster overall V̇O2 kinetics consequent to a substantial reduction in the V̇O2SC (0.27 ± 0.12 vs. 0.11 ± 0.09 L·min−1, P < 0.05) with an unchanged primary V̇O2 time constant. An increased baseline for the primed bout [total (Hb + Mb)] (197.5 ± 21.6 vs. 210.7 ± 22.5 μmol L−1, P < 0.01), reflecting increased microvascular [Hb] volume, correlated significantly with the V̇O2SC reduction. At multiple sites within the quadriceps femoris, priming exercise reduced the baseline and slowed the increase in [deoxy (Hb + Mb)]. Changes in the intersite coefficient of variation in the time delay and time constant of [deoxy (Hb + Mb)] during the second bout were not correlated with the V̇O2SC reduction. These results support a mechanistic link between priming exercise-induced increase in muscle [Hb] volume and the reduced V̇O2SC that serves to speed overall V̇O2 kinetics. However, reduction in the heterogeneity of muscle deoxygenation kinetics does not appear to be an obligatory feature of the priming response. PMID:26109190

Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages.

PubMed

Kizaki, Takako; Maegawa, Taketeru; Sakurai, Takuya; Ogasawara, Jun-etsu; Ookawara, Tomomi; Oh-ishi, Shuji; Izawa, Tetsuya; Haga, Shukoh; Ohno, Hideki

2011-09-30

Chronic low-level inflammation is associated with obesity and a sedentary lifestyle, causing metabolic disturbances such as insulin resistance. Exercise training has been shown to decrease chronic low-level systemic inflammation in high-fat diet (HFD)-induced obesity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Ghrelin is a peptide hormone predominantly produced in the stomach that stimulates appetite and induces growth hormone release. In addition to these well-known functions, recent studies suggest that ghrelin localizes to immune cells and exerts an anti-inflammatory effect. The purpose of the current study was to investigate the role of ghrelin expressed in macrophages in the anti-inflammatory effects of voluntary exercise training. Expression of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP)-1 and F4/80 was increased in adipose tissue from mice fed a HFD (HFD mice) compared with mice fed a standard diet (SD mice), whereas the expression of these inflammatory cytokines was markedly decreased in mice performing voluntary wheel running during the feeding of a HFD (HFEx mice). The expression of TNF-α was also increased in peritoneal macrophages by a HFD and exercise training inhibited the increase of TNF-α expression. Interestingly, expression of ghrelin in peritoneal macrophages was decreased by a HFD and recovered by exercise training. Suppression of ghrelin expression by siRNA increased TNF-α expression and LPS-stimulated NF-κB activation in RAW264 cells, which is a macrophage cell line. TNF-α expression by stimulation with LPS was significantly suppressed in RAW264 cells cultured in the presence of ghrelin. These results suggest that ghrelin exerts potent anti-inflammatory effects in macrophages and functions as a mediator of the beneficial effects of exercise training. Copyright © 2011 Elsevier Inc. All rights reserved.

Adaptation to exercise in the cold.

PubMed

Shephard, R J

1985-01-01

The winter athlete has several potential tactics for sustaining body temperature in the face of severe cold. An increase in the intensity of physical activity may be counter-productive because of increased respiratory heat loss, increased air or water movement over the body surface, and a pumping of air or water beneath the clothing. Shivering can generate heat at a rate of 10 to 15 kJ/min, but it impairs skilled performance, while the resultant glycogen usage hastens the onset of fatigue and mental confusion. Non-shivering thermogenesis could arise in either brown adipose tissue or white fat. Brown adipose tissue generates heat by the action of free fatty acids in uncoupling mitochondrial electron transport, and by noradrenaline-induced membrane depolarisation and sodium pumping. The existence of brown adipose tissue in human adults is controversial, and although there are theoretical mechanisms of heat production in white fat, their contribution to the maintenance of body temperature is small. Acclimatisation to cold develops over the course of about 10 days, and in humans the primary change is an insulative, hypothermic type of response; this reflects the intermittent nature of most occupational and athletic exposures to cold. Nevertheless, with more sustained exposure to cold air or water, humans can apparently develop the humoral type of acclimatisation described in small mammals, with an increased output of noradrenaline and/or thyroxine. The associated mobilisation of free fatty acids suggests the possibility of using winter sport as a pleasant method of treating obesity. In men, a combination of moderate exercise and facial cooling induces a substantial fat loss over a 1- to 2-week period, with an associated ketonuria, proteinuria, and increase of body mass. Possible factors contributing to this fat loss include: (a) a small energy deficit; (b) the energy cost of synthesising new lean tissue; (c) energy loss through the storage and excretion of ketone bodies; (d) catecholamine-induced 'futile' metabolic cycles with increased resting metabolism; and (e) a specific reaction to cold dehydration. Current limitations for the clinical application of such treatment include uncertainty regarding optimal environmental conditions, concern over possible pathological reactions to cold, and suggestions of a less satisfactory fat mobilisation in female patients. Possible interactions between physical fitness and metabolic reactions to cold remain controversial.(ABSTRACT TRUNCATED AT 400 WORDS)

Supplementation with Hualian No. 4 wild bitter gourd (Momordica charantia Linn. var. abbreviata ser.) extract increases anti-fatigue activities and enhances exercise performance in mice

PubMed Central

HSIAO, Chien-Yu; CHEN, Yi-Ming; HSU, Yi-Ju; HUANG, Chi-Chang; SUNG, Hsin-Ching; CHEN, Sheng-Shih

2017-01-01

Hualian No. 4 wild bitter gourd (WBG) is a specific vegetable cultivated by the Hualien District Agricultural Research and Extension Station in Taiwan. WBG is commonly consumed as a vegetable and used as a popular folk medicine. However, few studies have demonstrated the effects of WBG supplementation on exercise performance, physical fatigue and the biochemical profile. The purpose of this study was to evaluate the potential beneficial effects of WBG extract on fatigue and ergogenic functions following physiological challenge. Three groups of male ICR mice (n=8 per group) were orally administered 0, 1 or 2.5 g/kg/day of WBG for 4 weeks. They were respectively designated the vehicle, WBG-1X and WBG-2.5X groups. WBG significantly decreased body weight (BW) and epididymal fat pad (EFP) weight. Concerning physical performance, WBG supplementation dose-dependently increased grip strength and endurance swimming time. Concerning anti-fatigue activity, WBG decreased levels of serum lactate, ammonia, creatine kinase and blood urea nitrogen, and economized glucose metabolism after acute exercise challenge. Glycogen in the liver and gastrocnemius muscle dose-dependently increased with WBG treatment. Concerning the biochemical profile, WBG treatment significantly decreased alanine aminotransferase (ALT), blood urea nitrogen (BUN) and urea acid (UA), and increased total protein (TP). Therefore, 4-week supplementation with WBG may decrease white adipose weight, enhance energy economy, increase glycogen storage to enhance exercise performance and reduce fatigue. PMID:28458274

The effect of aerobic versus strength-based training on high-sensitivity C-reactive protein in older adults.

PubMed

Martins, Raul A; Neves, Ana P; Coelho-Silva, Manuel J; Veríssimo, Manuel T; Teixeira, Ana Maria

2010-09-01

Increased levels of inflammatory markers, namely, high-sensitive C-reactive protein (hs-CRP), have been associated with several chronic diseases including atherosclerosis, type 2 diabetes and hypertension. Forty-five women and men aged >64 years participated in the study and were randomly assigned to two exercise intervention groups and a non-exercising control group. The participants assigned to the exercising groups followed a 16-week exercise protocol based either on aerobic training (AT) or strength training (ST) followed by a further 16 weeks off-training period. The control group (C) remained sedentary throughout the study. Evaluation of body mass, BMI, waist circumference, aerobic endurance, lower-body strength, upper-body strength, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol and hs-CRP were performed at baseline, after 16 weeks (post-training for the exercise groups) and at 32 weeks (follow-up). Both, AT and ST groups significantly increased functional fitness at the end of the exercise programs when compared to baseline values. hs-CRP concentrations were maintained throughout the study for the C group, while decreasing 10% at 16 weeks and 51% at 32 weeks for the AT group. In the ST group the hs-CRP concentrations decreased by 11 and 39% at 16 and 32 weeks, respectively. Decreases in hs-CRP concentrations were statistically significant for the AT and ST groups at the 32-week evaluation when compared to baseline. Reduction in hs-CRP concentrations seemed to be associated with strength gains and adiposity loss.

Swim training and the genetic expression of adipokines in monosodium glutamate-treated obese rats.

PubMed

Svidnicki, Paulo Vinicius; Leite, Nayara Carvalho; Vicari, Marcelo Ricardo; Almeida, Mara Cristina de; Artoni, Roberto Ferreira; Favero, Giovani Marino; Grassiolli, Sabrina; Nogaroto, Viviane

2015-06-01

The aim of this study was to evaluate the genetic expression of adipokines in the adipocytes of monosodium glutamate (MSG)-treated obese rats submitted to physical activity. Obesity was induced by neonatal MSG administration. Exercised rats (MSG and control) were subjected to swim training for 30 min for 10 weeks, whereas their respective controls remained sedentary. Total RNA was obtained from sections of the mesenteric adipose tissue of the rats. mRNA levels of adiponectin (Adipoq), tumor necrosis factor alpha (Tnf), peroxisome proliferator-activated receptor alpha (Ppara), and peroxisome proliferator-activated receptor gamma (Pparg) adipokines were quantified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). In the exercise-trained control group, the expression of Adipoq increased compared to the sedentary control, which was not observed in the MSG-obese rats. Increased levels of Tnf in MSG-obese rats were not reversed by the swim training. The expression of Ppara was higher in sedentary MSG-obese rats compared to the sedentary control. Swimming increased this adipokine expression in the exercise-trained control rats compared to the sedentary ones. mRNA levels of Pparg were higher in the sedentary MSG-rats compared to the sedentary control; however, the exercise did not influenced its expression in the groups analyzed. In conclusion, regular physical activity was not capable to correct the expression of proinflammatory adipokines in MSG-obese rat adipocytes.

The effect of exercise on obesity, body fat distribution and risk for type 2 diabetes.

PubMed

Goedecke, Julia H; Micklesfield, Lisa K

2014-01-01

It is well known that obesity is a major risk factor for type 2 diabetes (T2D), while exercise is known to reduce body fatness and attenuate the risk of T2D. The aim of this chapter is to examine the interactions between exercise, obesity and body fat distribution, and the risk for T2D. Firstly, we show that body fatness, in particular visceral adipose tissue (VAT) accumulation, is associated with insulin resistance and incident T2D. We then show that aerobic exercise of sufficient intensity and volume results in a decrease in body fat and VAT. Conversely, sedentary behavior and physical inactivity are associated with increased body fat and VAT. Finally, the chapter examines the interaction between physical activity (PA), obesity and risk for T2D and shows that both obesity and PA are significant independent predictors of incident T2D, but the magnitude of risk imparted by high levels of body fat is much greater than that of low levels of PA. Further, we show that obese physically active individuals are at greater risk for incident T2D than normal-weight physically inactive individuals. The mechanisms underlying this complex interaction include the ability of exercise to increase free fatty acid oxidation to match high rates of lipolysis associated with obesity, as well as the effects of exercise on adipokine, cytokine and myokine secretion. Exercise, of sufficient volume and intensity, is therefore recommended to reduce obesity, centralization of body fat, and risk of T2D.

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model.

PubMed

Diane, Abdoulaye; Kupreeva, Maria; Borthwick, Faye; Proctor, Spencer D; Pierce, W David; Vine, Donna F

2015-09-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age characterized by ovulatory dysfunction, hyperandrogenism and cardiometabolic risk. The overweight-obese PCOS phenotype appears to have exacerbated reproductive dysfunction and cardiometabolic risk. In overweight-obese adult women with PCOS, exercise and energy restricted diets have shown limited and inconsistent effects on both cardiometabolic indices and reproductive outcomes. We hypothesized that an early lifestyle intervention involving exercise and dietary energy restriction to prevent or reduce the propensity for adiposity would modulate reproductive indices and cardiometabolic risk in an obese PCOS-prone rodent model. Weanling obese PCOS-prone and Lean-Control JCR:LA-cp rodents were given a chow diet ad libitum or an energy-restricted diet combined with or without voluntary exercise (4  h/day) for 8 weeks. Dietary energy restriction and exercise lowered total body weight gain and body fat mass by 30% compared to free-fed sedentary or exercising obese PCOS-prone animals (P<0.01). Energy restriction induced an increase in exercise intensity compared to free-feeding plus exercise conditions. Energy restriction and exercise decreased fasting plasma triglycerides and apoB48 concentrations in obese PCOS-prone animals compared to free-fed and exercise or sedentary groups. The energy restriction and exercise combination in obese PCOS-prone animals significantly increased plasma sex-hormone binding globulin, hypothalamic cocaine-and amphetamine-regulated transcript (CART) and Kisspeptin mRNA expression to levels of the Lean-Control group, and this was further associated with improvements in estrous cyclicity. The combination of exercise and dietary energy restriction when initiated in early life exerts beneficial effects on cardiometabolic and reproductive indices in an obese PCOS-prone rodent model, and this may be associated with normalization of the hypothalamic neuropeptides, Kisspeptin and CART. © 2015 Society for Endocrinology.

The Effect of Diet or Exercise on Visceral Adipose Tissue in Overweight Youth.

PubMed

Vissers, Dirk; Hens, Wendy; Hansen, Dominique; Taeymans, Jan

2016-07-01

Excess visceral adipose tissue (VAT) in children with obesity is associated with the development of cardiovascular and metabolic disease. This meta-analysis investigated if lifestyle interventions can reduce VAT in overweight and obese youth. Pubmed, Cochrane, and PEDro were searched for clinical trials that objectively assessed VAT and included study arms with supervised diet, exercise, or a combination of both. If there was a no-therapy control group, the data of the control group and the intervention groups were used to meta-analyze the data. In all other cases, the preintervention and the postintervention data were used to meta-analyze. Effect sizes were calculated as standardized mean differences or changes of VAT and expressed as Hedges' g. The overall weighted mean effect size on VAT of all included interventions was -0.69 (95% confidence interval [CI] = -0.90 to -0.48) (P < 0.001). Subgroup analysis showed that the overall weighted mean effect size of diet-only interventions on VAT was 0.23 (95% CI = -0.22 to 0.68) (P = 0.311). Interventions that combined diet and exercise showed a pooled effect size on VAT of -0.55 (95% CI = -0.75 to -0.39) (P < 0.001). The pooled effect size of exercise-only interventions on VAT was -0.85 (95% CI = -1.20 to -0.57) (P < 0.001). Supervised exercise-only or combined diet and exercise interventions can reduce VAT in overweight and obese children and adolescents. The strongest effect was found in exercise-only groups. However, high-quality randomized controlled trials describing the effect of supervised dietary interventions on VAT in children are lacking.

The association among skeletal muscle phosphocreatine recovery, adiposity, and insulin resistance in children.

PubMed

Wells, Greg D; Banks, Laura; Caterini, Jessica E; Thompson, Sara; Noseworthy, Michael D; Rayner, Tammy; Syme, Catriona; McCrindle, Brian W; Hamilton, Jill

2017-04-01

Obesity is associated with cardiometabolic disturbances, which may have significant implications for musculoskeletal health and exercise tolerance. We sought to determine the association between muscle structure, function, and metabolism in adolescents across the weight spectrum. This cross-sectional case-control study included overweight and obese participants (n = 24) 8-18 years of age with a body mass index (BMI) ≥ 85th percentile for age and gender, and non-obese participants (n = 24) with a BMI < 85 th percentile. Body composition, physical activity, peak aerobic capacity, cardiometabolic blood markers and insulin resistance (measured by the homeostatic model assessment of insulin resistance, HOMA-IR), skeletal muscle mitochondrial oxidative capacity (via 31 Phosphorous-Magnetic Resonance Spectroscopy, 31 P-MRS, to assess phosphocreatine (PCr) recovery after exercise), and extramyocellular and intramyocellular lipid (IMCL) levels (via 1 Hydrogen-MRS) were assessed. Stepwise regression was performed to examine the factors associated with oxidative capacity. bese and overweight patients had similar age, height, and physical activity to non-obese controls, but obese and overweight participants exhibited higher insulin resistance. Obese and overweight participants had longer PCr recovery than non-obese controls following 5x30s of moderate-intensity exercise (51.2 ± 20.1 s vs. 23.9 ± 7.5 s, p = 0.004). In univariate correlation analysis, impaired PCr recovery was associated with a higher BMI z-score (r s  = 0.51, p < 0.001), circulating triglycerides (r s  = 0.41, p = 0.005), and HOMA-IR (r s  = 0.46, p = 0.001). In stepwise multivariate regression analysis, impaired PCr recovery was associated with a higher BMI z-score (β = 0.47, p = 0.002), but not insulin resistance (β = 0.07, p = 0.07) or circulating triglycerides (β = 0.16 p = 0.33). A slower phosphocreatine recovery following aerobic exercise is strongly associated with increasing adiposity. A slower metabolic recovery following aerobic exercise stress suggests that endurance exercise training in obese adolescents may be an optimal strategy to target exercise intolerance in this cohort. © 2016 World Obesity Federation.

Metabolic cross-talk between skeletal muscle and adipose tissue in high-intensity interval training vs. moderate-intensity continuous training by regulation of PGC-1α.

PubMed

Shirvani, Hossein; Arabzadeh, Ehsan

2018-02-26

An imbalance in the production of adipokines and myokines impairs the energy expenditure, increases adipocyte and develops metabolic pathologies. Physical exercise is able to regulate the secretion of myokines and adipokines. The present study considers the metabolic cross talk between skeletal muscle and adipose tissue in high-intensity interval training vs. moderate-intensity continuous training by regulation of PGC-1α. A sample of 32 male Wistar rats (8 weeks old with mean weight 250 ± 55 g) were divided into four groups randomly: control of base (CO), control of 8 weeks (CO8w), moderate-intensity continuous training (MICT), and high-intensity interval training (HIIT). The rats were fed with standard chow diet. The CO group was killed at the start of the study and the CO8w group was kept alive for the same time as the experimental groups, but did not participate in any exercise. MICT and HIIT groups for 8 weeks were placed under the moderate-intensity continuous training (15-60 min, with speed of 15-30 m/min) and high-intensity interval training (8-4 intense period for 1 min, with speed of 28-55 m/min, with 3-7 slow-intensity period for 1 min, with a speed of 12-30 m/min) for 8 weeks, respectively. To measure the levels of serum irisin, nesfatin, and resistin the ELISA method was used and real-time PCR method was used to evaluate the relative expression of soleus PGC-1α gene mRNA. The levels of irisin and nesfatin significantly increased in the HIIT compared with control groups (p = 0.001). Resistin values in both training groups showed a significant decrease compared to the control groups (p = 0.005). The level of PGC-1α gene expression in both HIIT and MICT groups was significantly increased in comparison with the control groups (p = 0.001). The results showed that HIIT and MICT increase the transcription of the PGC-1α gene and possibly the increased expression of this gene after HIIT and MICT plays a central role in the secretion of skeletal muscle myokines and adipokines of adipose tissue. No Level of evidence: Animal study.

Adiponectin and catecholamine concentrations during acute exercise in children with type 1 diabetes.

PubMed

2008-06-01

Adiponectin, an adipokine secreted by the adipocyte, is inversely related to adiposity and directly related to insulin sensitivity. In type 1 diabetes mellitus (T1DM), however, data thus far are contradictory. We investigated the relationship between adiponectin and exercise inT1DM. Forty-nine children (14.5 +/- 2.0 yr, range 8-17 yr) with T1DM on an insulin pump were studied during two 75-min exercise sessions with and without continuation of the basal rate within 4 wk. Adiponectin and epinephrine concentrations were measured before and during exercise. Mean preexercise adiponectin concentration was 11.2 +/- 4.7 mg/L (range 2.7-23.0 mg/L) with a mean absolute difference of 1.7 mg/L between the 2 d. Adiponectin concentrations did not change meaningfully during exercise (mean change: -0.1 +/- 1.2 mg/L; p = 0.17). Adiponectin correlated inversely with body mass index percentile (p = 0.02) but not with age, gender, duration of diabetes, hemoglobin A1c, or preexercise glucose. However, those with higher baseline adiponectin concentrations were less likely to become hypoglycemic during exercise, 36% becoming hypoglycemic when baseline adiponectin concentration was <10 mg/L, 42% when 10 to <15 mg/L, and 15% when > or =15 mg/L (p = 0.02). Baseline epinephrine concentrations were not associated with adiponectin, and in those whose nadir glucose was < or =100 mg/dL, there was no correlation between epinephrine response and adiponectin (p = 0.16). Adiponectin concentrations are stable from day to day, are not affected by acute exercise or metabolic control, and vary inversely with adiposity. Higher adiponectin concentration appears to be associated with a decrease in hypoglycemia risk during exercise. Further studies are needed to examine whether adiponectin protects against exercise-induced hypoglycemia by directly enhancing the oxidation of alternate fuels.

The effects of resistance training on metabolic health with weight regain.

PubMed

Warner, Shana O; Linden, Melissa A; Liu, Ying; Harvey, Benjamin R; Thyfault, John P; Whaley-Connell, Adam T; Chockalingam, Anand; Hinton, Pamela S; Dellsperger, Kevin C; Thomas, Tom R

2010-01-01

To determine whether resistance training effectively maintains improvements in cardiometabolic syndrome risk factors during weight regain, 9 individuals lost 4% to 6% of their body weight during an 8- to 12-week diet- and aerobic exercise-induced weight loss phase followed by a controlled weight regain phase (8-12 weeks), during which they regained approximately 50% of the lost weight while participating in a supervised resistance training program. Following weight loss (6.0%+/-0.3%), body mass index, body fat percentage, waist circumference, all abdominal adipose tissue depots, total cholesterol, low-density lipoprotein cholesterol, insulin, and homeostasis model assessment (HOMA) were significantly reduced, while quantitative insulin-sensitivity check index (QUICKI) and cardiorespiratory fitness (maximal oxygen consumption) significantly increased. During weight regain (48.3%+/-3.3% of lost weight), body fat percentage, waist circumference, and maximal oxygen consumption were maintained and muscular strength and lean body mass significantly increased. Abdominal adipose tissue depots, insulin, HOMA, and QUICKI did not significantly change after weight regain. Resistance training was effective in maintaining improvements in metabolic health during weight regain.

Physical training improves visceral adipose tissue health by remodelling extracellular matrix in rats with estrogen absence: a gene expression analysis.

PubMed

Duarte, Fernanda O; Gomes-Gatto, Camila do Valle; Oishi, Jorge C; Lino, Anderson Diogo de S; Stotzer, Uliana S; Rodrigues, Maria Fernanda C; Gatti da Silva, Guilherme H; Selistre-de-Araújo, Heloisa S

2017-08-01

Adipose tissue development is associated with modifications involving extracellular matrix remodelling, and metalloproteinases play a significant role in this process. Reduced circulating sexual hormones cause impacts on the size, morphology and functions of the adipose tissue, increasing susceptibility to diseases. This study investigated whether exercise training may be an alternative strategy to combat the effects promoted by estrogen decay through modulation in gene expression patterns in the extracellular matrix (ECM) of visceral adipose tissue of ovariectomized rats. Nulliparous rats (n = 40) were randomly distributed into four groups (n = 10/group): sham sedentary (Sh-S), sham resistance training (Sh-Rt), ovariectomized sedentary (Ovx-S) and ovariectomized resistance training (Ovx-Rt). The Sh-S animals did not have any type of training. The body mass and food intake, ECM gene expression, gelatinase MMP-2 activity and adipocyte area were measured. A lack of estrogen promoted an increase in body mass, food intake and the visceral, parametrial and subcutaneous adipocyte areas. The ovariectomy upregulated the expression of MMP-2, MMP-9, TGF-β, CTGF, VEGF-A and MMP-2 activity. On the other hand, resistance training decreased the body mass, food intake and the adipocyte area of the three fat depots analysed; upregulated TIMP-1, VEGF-A and MMP-2 gene expression; downregulated MMP-9, TGF-β and CTGF gene expression; and decreased the MMP-2 activity. We speculate that resistance training on a vertical ladder could play an important role in maintaining and remodelling ECM by modulation in the ECM gene expression and MMP-2 activity, avoiding its destabilization which is impaired by the lack of estrogen. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Exercise reverses metabolic syndrome in high-fat diet-induced obese rats.

PubMed

Touati, Sabeur; Meziri, Fayçal; Devaux, Sylvie; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

2011-03-01

Chronic consumption of a high-fat diet induces obesity. We investigated whether exercise would reverse the cardiometabolic disorders associated with obesity without it being necessary to change from a high- to normal-fat diet. Sprague-Dawley rats were placed on a high-fat (HFD) or control diet (CD) for 12 wk. HFD rats were then divided into four groups: sedentary HFD (HFD-S), exercise trained (motor treadmill for 12 wk) HFD (HFD-Ex), modified diet (HFD to CD; HF/CD-S), and exercise trained with modified diet (HF/CD-Ex). Cardiovascular risk parameters associated with metabolic syndrome were measured, and contents of aortic Akt, phospho-Akt at Ser (473), total endothelial nitric oxide synthase (eNOS), and phospho-eNOS at Ser (1177) were determined by Western blotting. Chronic consumption of HFD induced a metabolic syndrome. Exercise and dietary modifications reduced adiposity, improved glucose and insulin levels and plasma lipid profile, and exerted an antihypertensive effect. Exercise was more effective than dietary modification in improving plasma levels of thiobarbituric acid-reacting substance and in correcting the endothelium-dependent relaxation to acetylcholine and insulin. Furthermore, independent of the diet used, exercise increased Akt and eNOS phosphorylation. Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.

Physical activity and abdominal obesity in youth.

PubMed

Kim, YoonMyung; Lee, SoJung

2009-08-01

Childhood obesity continues to escalate despite considerable efforts to reverse the current trends. Childhood obesity is a leading public health concern because overweight-obese youth suffer from comorbidities such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, metabolic syndrome, and cardiovascular disease, conditions once considered limited to adults. This increasing prevalence of chronic health conditions in youth closely parallels the dramatic increase in obesity, in particular abdominal adiposity, in youth. Although mounting evidence in adults demonstrates the benefits of regular physical activity as a treatment strategy for abdominal obesity, the independent role of regular physical activity alone (e.g., without calorie restriction) on abdominal obesity, and in particular visceral fat, is largely unclear in youth. There is some evidence to suggest that, independent of sedentary activity levels (e.g., television watching or playing video games), engaging in higher-intensity physical activity is associated with a lower waist circumference and less visceral fat. Several randomized controlled studies have shown that aerobic types of exercise are protective against age-related increases in visceral adiposity in growing children and adolescents. However, evidence regarding the effect of resistance training alone as a strategy for the treatment of abdominal obesity is lacking and warrants further investigation.

[Irisin: a messenger from the gods?].

PubMed

Moreno, María; Moreno-Navarrete, José María; Fernández-Real, José Manuel

2014-01-01

Due to the need to understand the basis of the metabolic benefits of exercise, irisin was discovered a few years ago. This cytokine, secreted by skeletal muscle due to exercise, should have positive effects on energetic metabolism. In particular, it could act as a messenger on white adipose tissue, modifying its phenotype into the beige adipocyte, and increasing its thermogenic capacity. Since it was described, there have been numerous studies led to depict its function, with the aim of determining if irisin could become a therapeutic target in the context of diseases associated with a caloric excess, such as obesity and diabetes. In this review, the irisin discovery is summarized, along with its in vitro and in vivo effects described up until now. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels.

PubMed

Abbenhardt, C; McTiernan, A; Alfano, C M; Wener, M H; Campbell, K L; Duggan, C; Foster-Schubert, K E; Kong, A; Toriola, A T; Potter, J D; Mason, C; Xiao, L; Blackburn, G L; Bain, C; Ulrich, C M

2013-08-01

Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Overweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N = 118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45 min of moderate-to-vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Adiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, -40.1%, P < 0.0001; diet, -27.1%, P < 0.0001; exercise, -12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend = 0.0002; diet + exercise, P-trend = 0.0005) and directly associated with leptin (diet, P-trend < 0.0001; diet + exercise, P-trend < 0.0001). Weight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Serum concentrations and subcutaneous adipose tissue mRNA expression of omentin in morbid obesity and type 2 diabetes mellitus: the effect of very-low-calorie diet, physical activity and laparoscopic sleeve gastrectomy.

PubMed

Urbanová, M; Dostálová, I; Trachta, P; Drápalová, J; Kaválková, P; Haluzíková, D; Matoulek, M; Lacinová, Z; Mráz, M; Kasalický, M; Haluzík, M

2014-01-01

Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.

Longitudinal validity of abdominal adiposity assessment by regional bioelectrical impedance.

PubMed

Alvero-Cruz, José Ramón; García-Romero, Jerónimo C; Carrillo de Albornoz-Gil, Margarita; Jiménez, Manuel; Correas-Gomez, Lorena; Peñaloza, Piero; López-Fernández, Iván; Carnero, Elvis A

2018-03-20

The main goal of this study was to analyze the longitudinal agreement between changes in trunk and abdominal adiposity variables assessed by DXA and portable bioimpedance device (ViScan). A total of 44 women, enrolled in a 4-month exercise intervention, were included in this analysis. Trunk/abdominal compartments were assessed by ViScan and DXA. Adjusted correlations for age and FM at first assessment (pre) were utilized to perform concurrent validation among methods and completed with an agreement analysis. We observed significant differences between the changes detected by DXA and ViScan for %TFM (difference = -1.41%; p < 0.05), and proportional bias (Kendall's Tau = 0.53; p < 0.0001). Changes in abdominal adiposity were similar (difference = -0.1037 z-score units, p = 0.53), although there was proportional bias (Kendall's Tau = -0.24, p < 0.022). ViScan has a limited capability to evaluated changes in trunk and abdominal adiposity, at least for clinical purposes in adult women.

Abdominal fat sub-depots and energy expenditure: Magnetic resonance imaging study.

PubMed

Serfaty, Dana; Rein, Michal; Schwarzfuchs, Dan; Shelef, Ilan; Gepner, Yftach; Bril, Nitzan; Cohen, Noa; Shemesh, Elad; Sarusi, Benjamin; Kovsan, Julia; Kenigsbuch, Shira; Chassidim, Yoash; Golan, Rachel; Witkow, Shula; Henkin, Yaakov; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2017-06-01

We aimed to assess the association between the distinct abdominal sub-depots and resting energy expenditure (REE). We performed magnetic resonance imaging (MRI) to quantify abdominal visceral-adipose-tissue (VAT), deep-subcutaneous-adipose-tissue (deep-SAT), and superficial-subcutaneous-adipose-tissue (superficial-SAT). We measured REE by indirect-calorimetry. Non-exercise activity thermogenesis (NEAT) [1-3 metabolic equivalents (METs)] and exercise thermogenesis (activities of 4+MET S ) were estimated based on 6-days of accelerometry to assess total physical activity energy expenditure (PAEE). We studied 282 participants: 249 men [mean age = 47.4 years, body-mass-index (BMI) = 31 kg/m 2 , mean VAT proportion from total abdominal fat = 34.5%, mean superficial-SAT proportion from total abdominal fat = 24.3%] and 33 women (mean age = 51.2 years, BMI = 30.1 kg/m 2 , mean VAT proportion from total abdominal fat = 22.8%, mean superficial-SAT proportion from total abdominal fat = 37.8%). As expected, women had lower REE [by 32.4% (1488 ± 234 kcal/day vs. 1971 ± 257 kcal/day; p < 0.01)] and lower REE/kg [by 8% (19.6 ± 3 kcal/kg vs. 21.2 ± 2 kcal/kg; p < 0.01)] than men. Exercise and total PAEE were positively associated with REE/kg (p < 0.01 for both) and a positive correlation between NEAT and REE/kg was borderline (p = 0.056). Participants, in whom abdominal VAT was the dominant proportional depot, had higher REE (1964 ± 297 kcal/day vs. 1654 ± 352 kcal/day; p < 0.01) and higher REE∖kg (22.2 ± 2.3 kcal/kg/day vs. 19.6 ± 2.5 kcal/kg/day; p < 0.01) than participants in whom superficial-SAT was the largest proportional depot. In multivariate models, adjusted for age, gender and residual BMI, increased VAT proportion was independently associated with higher REE (β = 0.181; p = 0.05). Likewise, increased VAT proportion (β = 0.482; p < 0.01) remained independently associated with higher REE/kg. In this model younger age (β = -0.329; p < 0.01) was associated with higher REE/kg. Abdominal fat distribution patterns are associated with varying levels of resting energy expenditure, potentially reflecting different metabolic rates of adipose sub-depots and providing an anatomic/anthropometric link to physiological obese sub-phenotypes. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Advanced onset of puberty after metformin therapy in swine with thrifty genotype.

PubMed

Astiz, S; Gonzalez-Bulnes, A; Astiz, I; Barbero, A; Perez-Solana, M L; Garcia-Real, I

2014-09-01

The prevention and treatment of obesity in children is based on adequate nutrition and exercise plus antihyperglycaemic drugs. Currently, the incidence of childhood obesity is aggravated in ethnicities with thrifty genotype, but there is no available information on the effects of metformin therapy. The relative effects of lifestyle and metformin on patterns of growth, fattening, metabolic status and attainment of puberty were assessed in females of an obese swine model (Iberian gilts), allocated to three experimental groups (group A, obesogenic diet and scarce exercise; group DE, adequate diet and opportunity for exercise; and group DEM, adequate diet and opportunity for exercise plus metformin). Group A evidenced high weight, corpulence and adiposity, high plasma triglycerides and impairments of glucose regulation predisposing to insulin resistance. These features were favourably modulated by adequate lifestyle (group DE), and these effects were strengthened by metformin treatment (group DEM), which induced an improvement in body development by favouring muscle deposition. However, contrary to expectations, metformin advanced the onset of puberty. Metformin treatments would have positive effects on growth patterns, adiposity and metabolic features of young females from ethnicities with thrifty genotype or developing leptin resistance, but a negative effect by advancing the attainment of puberty. This study provides a warning regarding the use of metformin, without further studies, in girls from these ethnicities. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Organ-specific physiological responses to acute physical exercise and long-term training in humans.

PubMed

Heinonen, Ilkka; Kalliokoski, Kari K; Hannukainen, Jarna C; Duncker, Dirk J; Nuutila, Pirjo; Knuuti, Juhani

2014-11-01

Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

Compounds of psoriasis with obesity and overweight.

PubMed

Owczarczyk-Saczonek, Agnieszka; Placek, Waldemar

2017-08-24

Many epidemiological studies have confirmed the relationship of obesity and psoriasis, and it is believed that obesity is an independent risk factor for its development and is associated with a worse prognosis. Furthermore, the reduction of body weight, using low-calorie diet combined with exercise, reduces the severity of psoriasis.Visceral adipose tissue is the largest endocrine organ, producing proinflammatory cytokines (TNF-α, IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin). They participate in the development of dyslipidemia, insulin resistance, diabetes, and consequently of the cardiovascular diseases. Macrophages of visceral adipose tissue have a special role and they increase significantly in obesity. They are responsible for the development of inflammation in adipose tissue and produce inflammatory cytokines (TNF alpha, IL-6, Il-8, Il-17, Il-18, MCP-1) and other adipokines: resistin, visfatin, retinol-binding protein 4. This explains the concept of «psoriatic march «and observations of the frequent coexistence of psoriasis with obesity. Inflammation associated with systemic disease, fanned by pro-inflammatory cytokines and adipokines produced by the visceral adipose tissue lead to the development of insulin resistance, endothelial cell damage. Endothelial dysfunction predisposes to the formation of atherosclerotic plaques and faster development of cardiovascular events. Complication of obesity is the development of non-alcoholic fatty liver disease (NAFLD), which states twice as likely in patients with plaque psoriasis and is associated with the severity of the disease. Another consequence is the development of depression. Probably the proinflammatory cytokines can interact with metabolism of neurotransmitters. Obesity also has a significant impact on the treatment of psoriasis, increasing the risk of adverse effects of systemic drugs, reducing the efficacy of biological agents which dose should be adjusted to the weight of the patient. It is a factor responsible for the increased volume of distribution and it causes low titter of drug concentration.

Adipose tissue metabolic and inflammatory responses to a mixed meal in lean, overweight and obese men.

PubMed

Travers, Rebecca L; Motta, Alexandre C; Betts, James A; Thompson, Dylan

2017-02-01

Most of what we know about adipose tissue is restricted to observations derived after an overnight fast. However, humans spend the majority of waking hours in a postprandial (fed) state, and it is unclear whether increasing adiposity impacts adipose tissue responses to feeding. The aim of this research was to investigate postprandial responses in adipose tissue across varying degrees of adiposity. Thirty males aged 35-55 years with waist circumference 81-118 cm were divided equally into groups categorized as either lean, overweight or obese. Participants consumed a meal and insulinaemic, glycaemic and lipidaemic responses were monitored over 6 h. Subcutaneous adipose tissue samples were obtained at baseline and after 6 h to examine changes in gene expression and adipose tissue secretion of various adipokines. Following consumption of the meal, insulin and glucose responses were higher with increased adiposity (total AUC effects of group; p = 0.058 and p = 0.027, respectively). At 6 h, significant time effects reflected increases in IL-6 (F = 14.7, p = 0.001) and MCP-1 (F = 10.7, p = 0.003) and reduction in IRS2 adipose tissue gene expression (F = 24.6, p < 0.001), all independent of adiposity. Ex vivo adipokine secretion from adipose tissue explants remained largely unchanged after feeding. Increased systemic measures of postprandial metabolism with greater adiposity do not translate into increased inflammatory responses within adipose tissue. Instead, postprandial adipose tissue changes may represent a normal response to feeding or a (relatively) normalized response with increased adiposity due to either similar net exposure (i.e. per g of adipose) or reduced adipose tissue responsiveness.

Obesity, growth hormone and exercise.

PubMed

Thomas, Gwendolyn A; Kraemer, William J; Comstock, Brett A; Dunn-Lewis, Courtenay; Maresh, Carl M; Volek, Jeff S

2013-09-01

Growth hormone (GH) is regulated, suppressed and stimulated by numerous physiological stimuli. However, it is believed that obesity disrupts the physiological and pathological factors that regulate, suppress or stimulate GH release. Pulsatile GH has been potently stimulated in healthy subjects by both aerobic and resistance exercise of the right intensity and duration. GH modulates fuel metabolism, reduces total fat mass and abdominal fat mass, and could be a potent stimulus of lipolysis when administered to obese individuals exogenously. Only pulsatile GH has been shown to augment adipose tissue lipolysis and, therefore, increasing pulsatile GH response may be a therapeutic target. This review discusses the factors that cause secretion of GH, how obesity may alter GH secretion and how both aerobic and resistance exercise stimulates GH, as well as how exercise of a specific intensity may be used as a stimulus for GH release in individuals who are obese. Only five prior studies have investigated exercise as a stimulus of endogenous GH in individuals who are obese. Based on prior literature, resistance exercise may provide a therapeutic target for releasing endogenous GH in individuals who are obese if specific exercise programme variables are utilized. Biological activity of GH indicates that this may be an important precursor to beneficial changes in body fat and lean tissue mass in obese individuals. However, additional research is needed including what molecular GH variants are acutely released and involved at target tissues as a result of different exercise stimuli and what specific exercise programme variables may serve to stimulate GH in individuals who are obese.

Fatty acid kinetic responses to running above or below lactate threshold.

PubMed

Kanaley, J A; Mottram, C D; Scanlon, P D; Jensen, M D

1995-08-01

During running exercise above the lactate threshold (LT), it is unknown whether free fatty acid (FFA) mobilization can meet the energy demands for fatty acid oxidation. This study was performed to determine whether FFA availability is reduced during running exercise above compared with below the LT and to assess whether the level of endurance training influences FFA mobilization. Twelve marathon runners and 12 moderately trained runners ran at a workload that was either above or below their individual LT. Fatty acid oxidation (indirect calorimetry) and FFA release ([1-14C]palmitate) were measured at baseline, throughout exercise, and at recovery. The plasma FFA rate of appearance increased during exercise in both groups; running above or below the LT, but the total FFA availability for 30 min of exercise was greater (P < 0.01) in the below LT group (marathon, 23 +/- 2 mmol; moderate, 21 +/- 2 mmol) than in the above LT group (18 +/- 3 and 13 +/- 3 mmol, respectively). Total fatty acid oxidation (indirect calorimetry) greatly exceeded circulating FFA availability, regardless of training or exercise group (P < 0.01). No statistically significant exercise intensity or training differences in fatty acid oxidation were found (above LT: marathon, 71 +/- 12, moderate, 64 +/- 17 mmol/30 min; below LT: marathon 91 +/- 12, moderate, 60 +/- 5 mmol/30 min). In conclusion, during exercise above or below LT, circulating FFA cannot meet the oxidative needs and intramuscular triglyceride stores must be utilized. Further marathon training does not enhance effective adipose tissue lipolysis during exercise compared with moderate endurance training.

Biological mechanisms underlying the role of physical fitness in health and resilience

PubMed Central

Silverman, Marni N.; Deuster, Patricia A.

2014-01-01

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex. PMID:25285199

Biological mechanisms underlying the role of physical fitness in health and resilience.

PubMed

Silverman, Marni N; Deuster, Patricia A

2014-10-06

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex.

Six months training alone or combined with diet alters HOMA-AD, HOMA-IR and plasma and adipose tissue adiponectin in obese women.

PubMed

Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

2014-01-01

We investigate the effect of 6 months aerobic training alone or in combination with diet on adiponectin in circulation and in adipose abdominal tissue (AT) in obese women. Twenty obese subjects were randomized into a 24 weeks intervention: 1) training (TR) and 2) training and diet (TRD). Blood samples were collected at baseline, after 12 wk and 24 wk. AT biopsies were obtained only at baseline and after 24 wk. In the TRD group the fat loss was after 12 wk -13.74% (p<0.01) and after 24 wk -21.82% (p<0.01) with no changes in the TR group. After 12 and 24 wk, VO2max was increased by 21.81-39.54% (p<0.05) in the TRD group and 18.09-40.95% in the TR group (p<0.05). After 12 wk, plasma adiponectin was raised only in the TRD group (55.8%, p<0.05). After 24 weeks, circulating adiponectin was elevated by 110.4% (p<0.01) in the TRD group and by 27% (p<0.05) in the TR group. In AT biopsies, subjects in the TRD and TR groups exhibited a significant increase in adiponectin (p<0.05 and p<0.01, respectively). The two indices HOMA-IR and HOMA-AD for assessing insulin resistance were strongly affected by protocols. HOMA-IR decreased (p<0.05) only after 24 wk in the TRD group. HOMA-AD increased in both groups after 12 (p<0.05) and 24 wk (p<0.01). Six months chronic aerobic exercise alone or combined with diet result in a significant increase in circulating and adipose tissue adiponectin levels in obese women independent of changes in body composition and/or in HOMA-IR.

Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

PubMed Central

Picklo, Matthew J.; Thyfault, John P.

2016-01-01

Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation. PMID:25761734

Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity.

PubMed

Lőrincz, Kende; Haluszka, Dóra; Kiss, Norbert; Gyöngyösi, Nóra; Bánvölgyi, András; Szipőcs, Róbert; Wikonkál, Norbert M

2017-04-01

Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability to detect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.

Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension

PubMed Central

Engeli, Stefan; Stinkens, Rudi; Heise, Tim; May, Marcus; Goossens, Gijs H.; Blaak, Ellen E.; Havekes, Bas; Jax, Thomas; Albrecht, Diego; Pal, Parasar; Tegtbur, Uwe; Haufe, Sven; Langenickel, Thomas H.

2018-01-01

Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks’ treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine. This was a multicenter, randomized, double-blind, active-controlled, parallel-group study enrolling subjects with abdominal obesity and moderate hypertension (mean sitting systolic blood pressure ≥130–180 mm Hg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3-2H]-glycerol tracer kinetics. Energy expenditure and substrate oxidation were measured simultaneously using indirect calorimetry. Plasma nonesterified fatty acids, glycerol, insulin, glucose, adrenaline and noradrenaline concentrations, blood pressure, and heart rate were also determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial glycerol concentrations and increased the rate of glycerol appearance. However, exercise-induced stimulation of lipolysis was not augmented on sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore, sacubitril/valsartan did not alter energy expenditure and substrate oxidation during exercise compared with amlodipine treatment. In conclusion, sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant changes in exercise-induced lipolysis or substrate oxidation in obese patients with hypertension, implying that its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864. PMID:29180454

Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension.

PubMed

Engeli, Stefan; Stinkens, Rudi; Heise, Tim; May, Marcus; Goossens, Gijs H; Blaak, Ellen E; Havekes, Bas; Jax, Thomas; Albrecht, Diego; Pal, Parasar; Tegtbur, Uwe; Haufe, Sven; Langenickel, Thomas H; Jordan, Jens

2018-01-01

Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks' treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine. This was a multicenter, randomized, double-blind, active-controlled, parallel-group study enrolling subjects with abdominal obesity and moderate hypertension (mean sitting systolic blood pressure ≥130-180 mm Hg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3- 2 H]-glycerol tracer kinetics. Energy expenditure and substrate oxidation were measured simultaneously using indirect calorimetry. Plasma nonesterified fatty acids, glycerol, insulin, glucose, adrenaline and noradrenaline concentrations, blood pressure, and heart rate were also determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial glycerol concentrations and increased the rate of glycerol appearance. However, exercise-induced stimulation of lipolysis was not augmented on sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore, sacubitril/valsartan did not alter energy expenditure and substrate oxidation during exercise compared with amlodipine treatment. In conclusion, sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant changes in exercise-induced lipolysis or substrate oxidation in obese patients with hypertension, implying that its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864. © 2017 The Authors.

Exercise Reduces Liver Lipids and Visceral Adiposity in Patients With Nonalcoholic Steatohepatitis in a Randomized Controlled Trial.

PubMed

Houghton, David; Thoma, Christian; Hallsworth, Kate; Cassidy, Sophie; Hardy, Timothy; Burt, Alastair D; Tiniakos, Dina; Hollingsworth, Kieren G; Taylor, Roy; Day, Christopher P; McPherson, Stuart; Anstee, Quentin M; Trenell, Michael I

2017-01-01

Pharmacologic treatments for nonalcoholic steatohepatitis (NASH) are limited. Lifestyle interventions are believed to be effective in reducing features of NASH, although the effect of regular exercise, independent of dietary change, is unclear. We performed a randomized controlled trial to study the effect of exercise on hepatic triglyceride content (HTGC) and biomarkers of fibrosis in patients with NASH. Twenty-four patients (mean age, 52 ± 14 y; body mass index, 33 ± 6 kg/m 2 ) with sedentary lifestyles (<60 min/wk of moderate-vigorous activity) and biopsy-proven NASH were assigned randomly to groups that exercised (n = 12) or continued standard care (controls, n = 12) for 12 weeks while maintaining their weight. The exercise (cycling and resistance training) was supervised at an accredited sports center and supervised by a certified exercise specialist and recorded 3 times per week on nonconsecutive days. We measured HTGC, body composition, circulating markers of inflammation, fibrosis, and glucose tolerance at baseline and at 12 weeks. Compared with baseline, exercise significantly reduced HTGC (reduction of 16% ± 24% vs an increase of 9% ± 15% for controls; P < .05), visceral fat (reduction of 22 ± 33 cm 2 vs an increase of 14 ± 48 cm 2 for controls; P < .05), plasma triglycerides (reduction of 0.5 ± 1.0 mmol/L vs an increase of 0.3 ± 0.4 mmol/L for controls; P < .05), and γ-glutamyltransferase (reduction of 10 ± 28 U/L - 1 vs a reduction of 17 ± 38 U/L -1 for controls; P < .05). There were no effects of exercise on liver enzyme levels, metabolic parameters, circulatory markers of inflammation (levels of interleukin 6, tumor necrosis factor-α, or C-reactive protein) and fibrosis. In a randomized controlled trial, 12 weeks of exercise significantly reduced HTGC, visceral fat, and plasma triglyceride levels in patients with NASH, but did not affect circulating markers of inflammation or fibrosis. Exercise without weight loss therefore affects some but not all factors associated with NASH. Clinical care teams should consider exercise as part of a management strategy of NASH, but weight management strategies should be included. Larger and longer-term studies are required to determine the effects of exercise in patients with NASH. ISRCTN registry.com: ISRCTN16070927. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Abalation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues

USDA-ARS?s Scientific Manuscript database

Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show ...

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with amore » high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.« less

Sustained, Low-Intensity Exercise Achieved by a Dynamic Feeding System Decreases Body Fat in Ponies.

PubMed

de Laat, M A; Hampson, B A; Sillence, M N; Pollitt, C C

2016-09-01

Obesity in horses is increasing in prevalence and can be associated with insulin insensitivity and laminitis. Current treatment strategies for obesity include dietary restriction and exercise. However, whether exercise alone is effective for decreasing body fat is uncertain. Our hypothesis was that twice daily use of a dynamic feeding system for 3 months would induce sustained, low-intensity exercise thereby decreasing adiposity and improving insulin sensitivity (SI). Eight, university-owned, mixed-breed, adult ponies with body condition scores (BCS) ≥5/9 were used. Two treatments ("feeder on" or "feeder off") were administered for a 3-month period by a randomized, crossover design (n = 4/treatment). An interim equilibration period of 6 weeks at pasture separated the 2 study phases. Measurements of body mass (body weight, BCS, cresty neck score [CrNS], and morphometry), body fat (determined before and after the "feeder on" treatment only), triglycerides, and insulin sensitivity (SI; combined glucose-insulin test) were undertaken before and after treatments. The dynamic feeding system induced a 3.7-fold increase in the daily distance travelled (n = 6), compared to with a stationary feeder, which significantly decreased mean BCS (6.53 ± 0.94 to 5.38 ± 1.71), CrNS (2.56 ± 1.12 to 1.63 ± 1.06) and body fat (by 4.95%). An improvement in SI did not occur in all ponies. A dynamic feeding system can be used to induce sustained (daily), low-intensity exercise that promotes weight loss in ponies. However, this exercise may not be sufficient to substantially improve SI. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effects of intermittent fasting and chronic swimming exercise on body composition and lipid metabolism.

PubMed

Moraes, Ruan Carlos Macedo de; Portari, Guilherme Vannucchi; Ferraz, Alex Soares Marreiros; da Silva, Tiago Eugênio Oliveira; Marocolo, Moacir

2017-12-01

Intermittent fasting protocol (IFP) has been suggested as a strategy to change body metabolism and improve health. The effects of IFP seem to be similar to aerobic exercise, having a hormetic adaptation according to intensity and frequency. However, the effects of combining both interventions are still unknown. Therefore, the aim of the present study was to evaluate the effects of IFP with and without endurance-exercise training on body composition, food behavior, and lipid metabolism. Twenty-week-old Wistar rats were kept under an inverted circadian cycle of 12 h with water ad libitum and assigned to 4 different groups: control group (ad libitum feeding and sedentary), exercise group (ad libitum feeding and endurance training), intermittent fasting group (IF; intermittent fasting and sedentary), and intermittent fasting and exercise group (IFEX; intermittent fasting and endurance training). After 6 weeks, the body weight of IF and IFEX animals decreased without changes in food consumption. Yet, the body composition between the 2 groups was different, with the IFEX animals containing higher total protein and lower total fat content than the IF animals. The IFEX group also showed increases in total high-density lipoprotein cholesterol and increased intramuscular lipid content. The amount of brown adipose tissue was higher in IF and IFEX groups; however, the IFEX group showed higher expression levels of uncoupling protein 1 in this tissue, indicating a greater thermogenesis. The IFP combined with endurance training is an efficient method for decreasing body mass and altering fat metabolism, without inflicting losses in protein content.

Effect of different exercise intensities on the pancreas of animals with metabolic syndrome.

PubMed

Amaral, Fernanda; Lima, Nathalia Ea; Ornelas, Elisabete; Simardi, Lucila; Fonseca, Fernando Luiz Affonso; Maifrino, Laura Beatriz Mesiano

2015-01-01

Metabolic syndrome (MS) comprises several metabolic disorders that are risk factors for cardiovascular disease and has its source connected to the accumulation of visceral adipose tissue (VAT) and development of insulin resistance. Despite studies showing beneficial results of exercise on several risk factors for cardiovascular disease, studies evaluating the effects of different intensities of exercise training on the pancreas with experimental models are scarce. In total, 20 Wistar rats were used, divided into four groups: control (C), metabolic syndrome (MS and without exercise), metabolic syndrome and practice of walking (MSWalk), and metabolic syndrome and practice of running (MSRun). The applied procedures were induction of MS by fructose in drinking water; experimental protocol of walking and running; weighing of body mass and VAT; sacrifice of animals with blood collection and removal of organs and processing of samples for light microscopy using the analysis of volume densities (Vv) of the studied structures. Running showed a reduction of VAT weight (-54%), triglyceride levels (-40%), Vv[islet] (-62%), Vv[islet.cells] (-22%), Vv[islet.insterstitial] (-44%), and Vv[acinar.insterstitial] (-24%) and an increase of Vv[acini] (+21%) and Vv[acinar.cells] (+22%). Regarding walking, we observed a decrease of VAT weight (-34%) and triglyceride levels (-27%), an increase of Vv[islet.cells] (+72%) and Vv[acinar.cells] (+7%), and a decrease of Vv[acini] (-4%) and Vv[acinar.insterstitial] (-16%) when compared with those in the MS group. Our results suggest that the experimental model with low-intensity exercise (walking) seems to be more particularly recommended for preventing morphological and metabolic disorders occurring in the MS.

Basal body temperature as a biomarker of healthy aging.

PubMed

Simonsick, Eleanor M; Meier, Helen C S; Shaffer, Nancy Chiles; Studenski, Stephanie A; Ferrucci, Luigi

2016-12-01

Scattered evidence indicates that a lower basal body temperature may be associated with prolonged health span, yet few studies have directly evaluated this relationship. We examined cross-sectional and longitudinal associations between early morning oral temperature (95.0-98.6 °F) and usual gait speed, endurance walk performance, fatigability, and grip strength in 762 non-frail men (52 %) and women aged 65-89 years participating in the Baltimore Longitudinal Study of Aging. Since excessive adiposity (body mass index ≥35 kg/m 2 or waist-to-height ratio ≥0.62) may alter temperature set point, associations were also examined within adiposity strata. Overall, controlling for age, race, sex, height, exercise, and adiposity, lower temperature was associated with faster gait speed, less time to walk 400 m quickly, and lower perceived exertion following 5-min of walking at 0.67 m/s (all p ≤ 0.02). In the non-adipose (N = 662), these associations were more robust (all p ≤ 0.006). Direction of association was reversed in the adipose (N = 100), but none attained significance (all p > 0.22). Over 2.2 years, basal temperature was not associated with functional change in the overall population or non-adipose. Among the adipose, lower baseline temperature was associated with greater decline in endurance walking performance (p = 0.006). In longitudinal analyses predicting future functional performance, low temperature in the non-adipose was associated with faster gait speed (p = 0.021) and less time to walk 400 m quickly (p = 0.003), whereas in the adipose, lower temperature was associated with slower gait speed (p = 0.05) and more time to walk 400 m (p = 0.008). In older adults, lower basal body temperature appears to be associated with healthy aging in the absence of excessive adiposity.

Effects of acute exercise on postprandial triglyceride response after a high fat meal in overweight black and white adolescents

PubMed Central

Lee, SoJung; Burns, Stephen F.; White, David; Kuk, Jennifer L.; Arslanian, Silva

2014-01-01

Objective We examined the effects of acute exercise on postprandial triglyceride (TG) metabolism following a high fat meal in overweight black vs. white adolescents. Design and Subjects Twenty-one black and 17 white adolescents (12-18 yrs, BMI >85th percentile) were evaluated twice, during control versus exercise trials, 1-4 weeks apart, in a counterbalanced randomized design. In the control trial, participants performed no exercise on day 1. In the exercise trial, participants performed a single bout of 60 min exercise (50% VO2peak) on a cycle ergometer on day 1. On day 2 of both trials, participants consumed a high-fat breakfast (70% calories from fat) and blood was sampled for TG concentration in the fasted state and for 6 hrs postprandially. Results There was a significant main effect of condition on postprandial peak TG concentration (P=0.01) and TG-area under the curve (AUC) (P=0.003), suggesting that independent of race, peak TG and TG-AUC was lower in the exercise trial vs. control trial. Including Tanner stage, gender, total fat (kg) and VAT as independent variables, stepwise multiple regression analyses revealed that in whites, VAT was the strongest (P<0.05) predictor of postprandial TG-AUC explaining 56% and 25% of the variances in TG-AUC in the control and exercise trials, respectively. In blacks, VAT was not associated with postprandial TG-AUC independent of trial. Conclusion A single bout of aerobic exercise preceding a high fat meal is beneficial to reduce postprandial TG concentrations in overweight white adolescents to a greater extent than black adolescents, particularly those with increased visceral adiposity. PMID:23507997

Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods.

PubMed

Dieli-Conwright, Christina M; Mortimer, Joanne E; Schroeder, E Todd; Courneya, Kerry; Demark-Wahnefried, Wendy; Buchanan, Thomas A; Tripathy, Debu; Bernstein, Leslie

2014-04-03

Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments. This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform intervention programs that will optimally improve physiological and psychosocial health during cancer survivorship, and that are ultimately aimed at improving prognosis. NCT01140282; June 10, 2010.

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program.

PubMed

Nascimento, Henrique; Costa, Elísio; Rocha, Susana; Lucena, Clarice; Rocha-Pereira, Petronila; Rêgo, Carla; Mansilha, Helena Ferreira; Quintanilha, Alexandre; Aires, Luísa; Mota, Jorge; Santos-Silva, Alice; Belo, Luís

2014-08-01

Adiponectin circulates as low-, medium-, and high-molecular-weight multimers (LMW, MMW, and HMW) and influences lipid profile and insulin resistance (IR), HMW being considered as the most biologically active form. We aimed to study the relation between adiponectin and markers of metabolic syndrome (MS) in pediatric obesity, and the impact of physical exercise. The study consisted of a cross-sectional part and an 8-mo physical exercise program. Lipid profile, insulin, glucose, C-reactive protein (CRP), total adiponectin (TA), and homeostasis model assessment IR (HOMA-IR) were measured. Adiponectin multimers were studied in a prepubertal group. Obesity is associated with increased dyslipidemia, IR, and inflammation. TA is correlated inversely with adiposity, triglycerides, HOMA-IR, and CRP, and positively with high-density lipoprotein cholesterol (HDLc)/total cholesterol (TC) ratio. HMW mimicked TA associations. The intervention program led to a reduction of TC, low-density lipoprotein cholesterol (LDLc), insulin, HOMA-IR, and trunk percentage of fat, and an increase of HDLc/TC ratio, in the obese group. BMI improvements prevented adiponectin reduction and correlated with increments in HMW and MMW. Obesity-related increase in MS features might be linked to lower adiponectin. HMW and MMW were the multimers that most explained the MS features. The intervention program improved the lipid profile and IR, and prevented the reduction of adiponectin.

Visceral adiposity index as an indicator of cardiometabolic risk in patients treated for craniopharyngioma.

PubMed

Ferraù, Francesco; Spagnolo, Federica; Cotta, Oana Ruxandra; Cannavò, Laura; Alibrandi, Angela; Russo, Giuseppina Tiziana; Aversa, Tommaso; Trimarchi, Francesco; Cannavò, Salvatore

2017-11-01

Craniopharyngioma is associated with metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index has been proposed as a marker of visceral adipose tissue dysfunction and of the related cardiometabolic risk. The role of the visceral adiposity index has never been explored in craniopharyngioma patients. We assessed the cardiometabolic risk on the basis of the visceral adiposity index in craniopharyngioma patients. We evaluated data of 24 patients treated for craniopharyngioma in a single-centre. We investigated the relationship among patients' clinical and biochemical features, cardiovascular risk -assessed by the Framingham and the atherosclerotic cardiovascular disease risk scores-, visceral adiposity index and adipose tissue dysfunction severity. Increased visceral adiposity index was found in 8 patients (33%). Adipose tissue dysfunction resulted to be severe, moderate or mild in 5, 2 and 1 cases. Increased visceral adiposity index significantly correlated with the occurrence of metabolic syndrome (p 0.027), IRI (p 0.001), triglycerides (p < 0.001), HOMA-IR (p < 0.001) and with lower ISI-Matsuda (p 0.005) and HDL-cholesterol (p < 0.001). Higher degree of adipose tissue dysfunction associated with increased insulin resistance. No gender difference was found for visceral adiposity index, adipose tissue dysfunction severity, and cardiovascular risk scores. Patients with adulthood onset craniopharyngioma showed higher Framingham risk score (p 0.004), atherosclerotic cardiovascular disease 10-year (p < 0.001) and lifetime (p 0.018) risk scores than those with childhood onset disease. Visceral adiposity index is increased in one third of our patients with craniopharyngioma, even if metabolic syndrome does not occur. Increased visceral adiposity index and adipose tissue dysfunction severity correlate with insulin sensitivity parameters, do not correlate with Framingham or atherosclerotic cardiovascular disease risk scores, and are not influenced by gender and age of disease onset.

Irisin exerts dual effects on browning and adipogenesis of human white adipocytes.

PubMed

Zhang, Yuan; Xie, Chao; Wang, Hai; Foss, Robin M; Clare, Morgan; George, Eva Vertes; Li, Shiwu; Katz, Adam; Cheng, Henrique; Ding, Yousong; Tang, Dongqi; Reeves, Westley H; Yang, Li-Jun

2016-08-01

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes "browning" of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.

Ovariectomized Highly Fit Rats Are Protected against Diet-Induced Insulin Resistance.

PubMed

Park, Young-Min; Kanaley, Jill A; Zidon, Terese M; Welly, Rebecca J; Scroggins, Rebecca J; Britton, Steven L; Koch, Lauren G; Thyfault, John P; Booth, Frank W; Padilla, Jaume; Vieira-Potter, Victoria J

2016-07-01

In the absence of exercise training, rats selectively bred for high intrinsic aerobic capacity (high-capacity running (HCR)) are protected against ovariectomy (OVX)-induced insulin resistance (IR) and obesity compared with those bred for low intrinsic aerobic capacity (low-capacity running (LCR)). This study determined whether OVX HCR rats remain protected with exposure to high-fat diet (HFD) compared with OVX LCR rats. Female HCR and LCR rats (n = 36; age, 27-33 wk) underwent OVX and were randomized to a standard chow diet (NC, 5% kcal fat) or HFD (45% kcal fat) ad libitum for 11 wk. Total energy expenditure, resting energy expenditure, spontaneous physical activity (SPA), and glucose tolerance were assessed midway, whereas fasting circulating metabolic markers, body composition, adipose tissue distribution, and skeletal muscle adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial markers were assessed at sacrifice. Both HCR and LCR rats experienced HFD-induced increases in total and visceral adiposity after OVX. Despite similar gains in adiposity, HCR rats were protected from HFD-induced IR and reduced total energy expenditure observed in LCR rats (P < 0.05). This metabolic protection was likely attributed to a compensatory increase in SPA and associated preservation of skeletal muscle AMPK activity in HCR; however, HFD significantly reduced SPA and AMPK activity in LCR (P < 0.05). In both lines, HFD reduced citrate synthase activity, gene expression of markers of mitochondrial biogenesis (tFAM, NRF1, and PGC-1α), and protein levels of mitochondrial oxidative phosphorylation complexes I, II, IV, and V in skeletal muscle (all P < 0.05). After OVX, HCR and LCR rats differentially respond to HFD such that HCR increase while LCR decrease SPA. This "physical activity compensation" likely confers protection from HFD-induced IR and reduced energy expenditure in HCR rats.

VEGF and VEGFB Play Balancing Roles in Adipose Differentiation, Gene Expression, and Function.

PubMed

Jin, Honghong; Li, Dan; Wang, Xutong; Jia, Jia; Chen, Yang; Yao, Yapeng; Zhao, Chunlan; Lu, Xiaodan; Zhang, Shujie; Togo, Jacques; Ji, Yan; Zhang, Luqing; Feng, Xuechao; Zheng, Yaowu

2018-05-01

Obesity is the result of abnormal adipose development and energy metabolism. Using vascular endothelial growth factor (VEGF) B-knockout and inducible VEGF downregulation mouse models, we have shown that VEGFB inactivation caused expansion of white adipose, whitening of brown adipose, an increase in fat accumulation, and a reduction in energy consumption. At the same time, expression of the white adipose-associated genes was increased and brown adipose-associated genes decreased. VEGF repression, in contrast, induced brown adipose expansion and brown adipocyte development in white adipose, increased energy expenditure, upregulated brown adipose-associated genes, and downregulated white adipose-associated genes. When VEGFB-knockout and VEGF-repressed mice are crossed together, VEGF and VEGFB can counteractively regulate large numbers of genes and efficiently reverse each other's roles. These genes, under counteractive VEGF and VEGFB regulations, include transcription factors, adhesion molecules, and metabolic enzymes. This balancing role is confirmed by morphologic and functional changes. This study reports that VEGF and VEGFB counteractively regulate adipose development and function in energy metabolism.

Advances in exercise, fitness, and performance genomics in 2012.

PubMed

Pérusse, Louis; Rankinen, Tuomo; Hagberg, James M; Loos, Ruth J F; Roth, Stephen M; Sarzynski, Mark A; Wolfarth, Bernd; Bouchard, Claude

2013-05-01

A small number of excellent articles on exercise genomics issues were published in 2012. A new PYGM knock-in mouse model will provide opportunities to investigate the exercise intolerance and very low activity level of people with McArdle disease. New reports on variants in ACTN3 and ACE have increased the level of uncertainty regarding their true role in skeletal muscle metabolism and strength traits. The evidence continues to accumulate on the positive effects of regular physical activity on body mass index or adiposity in individuals at risk of obesity as assessed by their FTO genotype or by the number of risk alleles they carry at multiple obesity-susceptibility loci. The serum levels of triglycerides and the risk of hypertriglyceridemia were shown to be influenced by the interactions between a single nucleotide polymorphism (SNP) in the NOS3 gene and physical activity level. Allelic variation at nine SNPs was shown to account for the heritable component of the changes in submaximal exercise heart rate induced by the HERITAGE Family Study exercise program. SNPs at the RBPMS, YWHAQ, and CREB1 loci were found to be particularly strong predictors of the changes in submaximal exercise heart rate. The 2012 review ends with comments on the importance of relying more on experimental data, the urgency of identifying panels of genomic predictors of the response to regular exercise and particularly of adverse responses, and the exciting opportunities offered by recent advances in our understanding of the global architecture of the human genome as reported by the Encyclopedia of DNA Elements project.

Advances in Exercise, Fitness, and Performance Genomics in 2012

PubMed Central

Pérusse, Louis; Rankinen, Tuomo; Hagberg, James M.; Loos, Ruth J. F.; Roth, Stephen M.; Sarzynski, Mark A.; Wolfarth, Bernd; Bouchard, Claude

2013-01-01

A small number of excellent papers on exercise genomics issues have been published in 2012. A new PYGM knock-in mouse model will provide opportunities to investigate the exercise intolerance and very low activity level of people with McArdle disease. New reports on variants in ACTN3 and ACE have increased the level of uncertainty regarding their true role in skeletal muscle metabolism and strength traits. The evidence continues to accumulate on the positive effects of regular physical activity on body mass index (BMI) or adiposity in individuals at risk of obesity as assessed by their FTO genotype or by the number of risk alleles they carry at multiple obesity-susceptibility loci. Serum levels of triglycerides and the risk of hypertriglyceridemia were shown to be influenced by the interactions between a single nucleotide polymorphism (SNP) in the NOS3 gene and physical activity level. Allelic variation at nine SNPs was shown to account for the heritable component of the changes in submaximal exercise heart rate induced by the HERITAGE Family Study exercise program. SNPs at the RBPMS, YWHAQ, and CREB1 loci were found to be particularly strong predictors of the changes in submaximal exercise heart rate. The 2012 review ends with comments on the importance of relying more on experimental data, the urgency of identifying panels of genomic predictors of the response to regular exercise and particularly of adverse responses, and the exciting opportunities offered by recent advances in our understanding of the global architecture of the human genome as reported by the ENCODE project. PMID:23470294

Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.

PubMed

Bagley, Heidi N; Wang, Yan; Campbell, Michael S; Yu, Xing; Lane, Robert H; Joss-Moore, Lisa A

2013-01-01

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

The metabolic syndrome as a concept of adipose tissue disease.

PubMed

Oda, Eiji

2008-07-01

The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to directly promote the development of diabetes and cardiovascular disease. However, in 2005, the American Diabetes Association and the European Association for the Study of Diabetes jointly stated that no existing definition of the metabolic syndrome meets the criteria of a syndrome, and there have been endless debates on the pros and cons of using the concept of this syndrome. The controversy may stem from confusion between the syndrome and obesity. Obesity is an epidemic, essentially contagious disease caused by an environment of excess nutritional energy and reinforced by deeply rooted social norms. The epidemic of obesity should be prevented or controlled by social and political means, similar to the approaches now being taken to combat global warming. The diagnosis of metabolic syndrome is useless for this public purpose. The purpose of establishing criteria for diagnosing metabolic syndrome is to find individuals who are at increased risk of diabetes and cardiovascular disease and who require specific therapy including diet and exercise. The syndrome may be an adipose tissue disease different from obesity; in that case, it would be characterized by inflammation clinically detected through systemic inflammatory markers such as high-sensitivity C-reactive protein and insulin resistance reflecting histological changes in adipose tissue. However, many problems in defining the optimal diagnostic criteria remain unresolved.

Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study.

PubMed

Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten; Harary Søndergaard, Rebekka; Follin, Bjarke; Drozd Lund, Lisbeth; Mønsted Johansen, Ellen; Ali Qayyum, Abbas; Bruun Mathiasen, Anders; Jørgensen, Erik; Helqvist, Steffen; Jørgen Elberg, Jens; Bruunsgaard, Helle; Ekblond, Annette

2017-11-01

The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen (HLA) class I antibodies, and two out of ten patients had donor-specific HLA antibodies already at baseline. There were no clinical symptoms or changes in inflammatory parameters in the follow-up period that indicated an ongoing immune response. There was a tendency toward improvement in cardiac function after CSCC_ASC treatment at 6-month follow-up: left ventricular end systolic volume decreased and left ventricular ejection fraction increased. In addition, exercise capacity increased. These changes were independent of the presence or absence of HLA antibodies. It is concluded that the newly developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials. Stem Cells Translational Medicine 2017;6:1963-1971. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Beneficial impact of exercise and obesity interventions on erectile function and its risk factors.

PubMed

Hannan, Johanna L; Maio, M Tina; Komolova, Marina; Adams, Michael A

2009-03-01

Erectile dysfunction (ED) is a multifaceted disease involving cardiovascular, metabolic, and hormonal factors and affects over 100 million men worldwide. ED has been shown to be a harbinger of underlying cardiovascular diseases (CVD), as there are common risk factors (aging, hypertension, obesity) and mechanistic basis. To provide an update on clinical and experimental evidence regarding the impact of lifestyle modifications, such as exercise and diet, with respect to changes in erectile function. Published evidence regarding the impact of aging, hypertension, and obesity on ED and CVD, as well as new experimental data linking obesity and diminished erectile responses. We reviewed the literature regarding common risk factors of ED and CVD, particularly involving obesity, as well as performed new analysis on the findings of other experimental studies involving diet and exercise interventions. Physical inactivity negatively impacts on erectile function, and experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health. Mediterranean-style diets and a reduction in caloric intake have been found to improve erectile function in men with the aspects of the metabolic syndrome. In addition, both clinical and experimental studies have confirmed that combining the two interventions provides additional benefit to erectile function, likely via reduced metabolic disturbances (e.g., inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (e.g., increased endothelial function). Lifestyle modifications provide significant benefits to vascular health and erectile function in a population that is increasingly aged and more obese.

Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice.

PubMed

Bernardo, Barbara L; Wachtmann, Timothy S; Cosgrove, Patricia G; Kuhn, Max; Opsahl, Alan C; Judkins, Kyle M; Freeman, Thomas B; Hadcock, John R; LeBrasseur, Nathan K

2010-06-25

Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice. Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.

The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus.

PubMed

Miele, Emily M; Headley, Samuel A E

2017-09-12

Aerobic exercise training is a component of diabetes mellitus (DM) care guidelines due to its favorable effects on glycemic control and cardiovascular disease (CVD) risk factors. The purpose of this review is to outline the recent evidence regarding the clinical effects of chronic aerobic exercise on CVD risk factors in persons with DM and to compare the effects of varying intensities and types of exercise. Among individuals with DM, all types of aerobic exercise training can impact positively on some traditional and non-traditional risk factors for CVD. Training programs with a higher volume or intensity induce greater improvements in vascular function, cardiorespiratory fitness (CRF), and lipid profiles. The beneficial outcomes of aerobic training include improvements in glycemic control, endothelial function, oxidative stress, dyslipidemia, myocardial function, adiposity, and CRF. Findings regarding markers of inflammation are discrepant and further research should focus on the role of exercise to impact upon the chronic inflammation associated with DM.

Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Fibronectin type III domain containing 5

PubMed Central

Mart, Ryan; Bond, Cherie E.

2014-01-01

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (FNDC5), the precursor for Irisin. Methods. We performed immunoblot analysis and quantitative real-time PCR analysis of Myonectin and FNDC5 in the diaphragm muscles of obese Zucker rat (OZR) and lean Zucker rat (LZR) with 9 weeks of aerobic training on a motorized treadmill. Results. We show that myonectin gene expression is increased in the OZR model of obesity and decreases with exercise in both lean and obese Zucker rats. Conversely, myonectin protein concentration was elevated with exercise. Similarly, FNDC5 mRNA levels are significantly higher in the OZR, however exercise training had no effect on the expression level of FNDC5 in either the LZR or OZR. We did not observe any difference in muscle protein content of Irisin with obesity or exercise. Conclusion. Our data shows that exercise training does not increase either FNDC5 or myonectin gene expression, indicating that increased transcriptional regulation of these myokines is not induced by exercise. However, our data also indicates a yet to be explored disconnect between myonectin gene expression and protein content. Further, this report highlights the importance of verifying reference genes when completing gene expression analysis. We found that many commonly used reference genes varied significantly by obesity and/or exercise and would have skewed the results of this study if used to normalize gene expression data. The unstable reference genes include: beta-Actin, beta-2-microglobulin, Non-POU domain containing, octamer-binding, Peptidylprolyl isomerase H, 18S ribosomal RNA, TATA box binding protein and Transferrin receptor. PMID:25289190

Impact of Preoperative Abdominal Visceral Adipose Tissue Area and Nutritional Status on Renal Function After Donor Nephrectomy in Japanese Living Donors for Renal Transplantation.

PubMed

Hori, Shunta; Miyake, Makito; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Tanaka, Nobumichi; Yoshida, Katsunori; Fujimoto, Kiyohide

2018-05-29

BACKGROUND Living kidney donors face the risk of renal dysfunction, resulting in end-stage renal disease, cardiovascular disease, or cerebrovascular disease, after donor nephrectomy. Reducing this risk is important to increasing survival of living donors. In this study, we investigated the effect of preoperative distribution of abdominal adipose tissue and nutritional status on postoperative renal function in living donors. MATERIAL AND METHODS Seventy-five living donors were enrolled in this retrospective study. Preoperative unenhanced computed tomography images were used to measure abdominal adipose tissue parameters. Prognostic nutritional index (PNI) was used to assess preoperative nutritional status. Donors were divided into 2 groups according to abdominal visceral adipose tissue (VAT) area at the level of the fourth and fifth lumbar vertebrae (<80 or ≥80 cm²). Postoperative renal function was compared in the 2 groups, and prognostic factors for development of chronic kidney disease (CKD) G3b were identified using multivariate analysis. RESULTS Donors with a VAT area ≥80 significantly more often had hypertension preoperatively. Although there was no significant difference in preoperative estimated glomerular filtration rate (eGFR) between the 2 groups, postoperative renal function was significantly decreased in donors with a VAT area ≥80 compared to those with a VAT area <80. In multivariate analysis, VAT area ≥80 and PNI <54 were independent factors predicting the development of CKD G3b after 12 months. CONCLUSIONS Our findings suggest that preoperative VAT and PNI affect postoperative renal function. Further research is required to establish appropriate exercise protocols and nutritional interventions during follow-up to improve outcomes in living donors.

Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable in response to a aerobic exercise training

PubMed Central

Han, Tae Kyung

2013-01-01

The purpose of the current study was to investigate whether or not the FABP2 gene polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers through 12-week aerobic exercise training in abdominal obesity group of Korean mid-life women. A total of 243 abdominally obese subjects of Korean mid-life women voluntarily participated in aerobic exercise training program for 12 weeks. Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise training program, baseline obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers were measured. All the measurements were replicated following the 12-week aerobic exercise training program, and then the following results were found. After 12-week aerobic exercise training program, wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P > .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001), RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P > .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P > .001) and significantly increased VO2max (P > .001). And wild type significantly decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and significantly increased HDLC (p > .005). Mutant type significantly decreased SBP (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA index (P > .01). The result of the present study represents that regular aerobic exercise training may beneficially prevent obesity index, blood pressure, blood lipids and insulin resistance markers independent of FABP Ala54Thr wild type and mutant type. PMID:25566432

Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats.

PubMed

Campbell, Jonathan E; Király, Michael A; Atkinson, Daniel J; D'souza, Anna M; Vranic, Mladen; Riddell, Michael C

2010-07-01

We determined the effects of voluntary wheel running on the hypothalamic-pituitary-adrenal (HPA) axis, and the peripheral determinants of glucocorticoids action, in male Zucker diabetic fatty (ZDF) rats. Six-week-old euglycemic ZDF rats were divided into Basal, Sedentary, and Exercise groups (n = 8-9 per group). Basal animals were immediately killed, whereas Sedentary and Exercising rats were monitored for 10 wk. Basal (i.e., approximately 0900 AM in the resting state) glucocorticoid levels increased 2.3-fold by week 3 in Sedentary rats where they remained elevated for the duration of the study. After an initial elevation in basal glucocorticoid levels at week 1, Exercise rats maintained low glucocorticoid levels from week 3 through week 10. Hyperglycemia was evident in Sedentary animals by week 7, whereas Exercising animals maintained euglycemia throughout. At the time of death, the Sedentary group had approximately 40% lower glucocorticoid receptor (GR) content in the hippocampus, compared with the Basal and Exercise groups (P < 0.05), suggesting that the former group had impaired negative feedback regulation of the HPA axis. Both Sedentary and Exercise groups had elevated ACTH compared with Basal rats, indicating that central drive of the axis was similar between groups. However, Sedentary, but not Exercise, animals had elevated adrenal ACTH receptor and steroidogenic acute regulatory protein content compared with the Basal animals, suggesting that regular exercise protects against elevations in glucocorticoids by a downregulation of adrenal sensitivity to ACTH. GR and 11beta-hydroxysteroid dehydrogenase type 1 content in skeletal muscle and liver were similar between groups, however, GR content in adipose tissue was elevated in the Sedentary groups compared with the Basal and Exercise (P < 0.05) groups. Thus, the gradual elevations in glucocorticoid levels associated with the development of insulin resistance in male ZDF rats can be prevented with regular exercise, likely because of adaptations that occur primarily in the adrenal glands.

The epigenetics of obesity: Role of diet and exercise on adipose, skeletal muscle, and placental tissue metabolism

USDA-ARS?s Scientific Manuscript database

Maternal undernutrition or consumption of excess food energy contributes to the subsequent development of obesity in offspring. This phenomenon, in part, involves the epigenetic transmission of obesity risk across generations. The primary aim of our study is to determine whether a maternal diet incr...

The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue

PubMed Central

Sakurai, Takuya; Ogasawara, Junetsu; Kizaki, Takako; Ishibashi, Yoshinaga; Takahashi, Motoko; Kobayashi, Osamu; Nagasawa, Junichi; Takahashi, Kazuto; Ishida, Hitoshi; Ohno, Hideki

2013-01-01

Obesity is recognized as a risk factor for lifestyle-related diseases such as type 2 diabetes and cardiovascular disease. White adipose tissue (WAT) is not only a static storage site for energy; it is also a dynamic tissue that is actively involved in metabolic reactions and produces humoral factors, such as leptin and adiponectin, which are collectively referred to as adipokines. Additionally, because there is much evidence that obesity-induced inflammatory changes in WAT, which is caused by dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein 1, contribute to the development of insulin resistance, WAT has attracted special attention as an organ that causes diabetes and other lifestyle-related diseases. Exercise training (TR) not only leads to a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the inflammation-related adipokines in WAT. Therefore, TR is widely used as a tool for preventing and improving lifestyle-related diseases. This review outlines the impact of TR on the expression and secretory response of adipokines in WAT. PMID:24369466

Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4.

PubMed

Drager, Luciano F; Yao, Qiaoling; Hernandez, Karen L; Shin, Mi-Kyung; Bevans-Fonti, Shannon; Gay, Jason; Sussan, Thomas E; Jun, Jonathan C; Myers, Allen C; Olivecrona, Gunilla; Schwartz, Alan R; Halberg, Nils; Scherer, Philipp E; Semenza, Gregg L; Powell, David R; Polotsky, Vsevolod Y

2013-07-15

Obstructive sleep apnea is a risk factor for dyslipidemia and atherosclerosis, which have been attributed to chronic intermittent hypoxia (CIH). Intermittent hypoxia inhibits a key enzyme of lipoprotein clearance, lipoprotein lipase, and up-regulates a lipoprotein lipase inhibitor, angiopoietin-like 4 (Angptl4), in adipose tissue. The effects and mechanisms of Angptl4 up-regulation in sleep apnea are unknown. To examine whether CIH induces dyslipidemia and atherosclerosis by increasing adipose Angptl4 via hypoxia-inducible factor-1 (HIF-1). ApoE(-/-) mice were exposed to intermittent hypoxia or air for 4 weeks while being treated with Angptl4-neutralizing antibody or vehicle. In vehicle-treated mice, hypoxia increased adipose Angptl4 levels, inhibited adipose lipoprotein lipase, increased fasting levels of plasma triglycerides and very low density lipoprotein cholesterol, and increased the size of atherosclerotic plaques. The effects of CIH were abolished by the antibody. Hypoxia-induced increases in plasma fasting triglycerides and adipose Angptl4 were not observed in mice with germline heterozygosity for a HIF-1α knockout allele. Transgenic overexpression of HIF-1α in adipose tissue led to dyslipidemia and increased levels of adipose Angptl4. In cultured adipocytes, constitutive expression of HIF-1α increased Angptl4 levels, which was abolished by siRNA. Finally, in obese patients undergoing bariatric surgery, the severity of nocturnal hypoxemia predicted Angptl4 levels in subcutaneous adipose tissue. HIF-1-mediated increase in adipose Angptl4 and the ensuing lipoprotein lipase inactivation may contribute to atherosclerosis in patients with sleep apnea.

The effect of endurance exercise on both skeletal muscle and systemic oxidative stress in previously sedentary obese men

PubMed Central

Samjoo, I A; Safdar, A; Hamadeh, M J; Raha, S; Tarnopolsky, M A

2013-01-01

Background: Obesity is associated with low-grade systemic inflammation, in part because of secretion of proinflammatory cytokines, resulting into peripheral insulin resistance (IR). Increased oxidative stress is proposed to link adiposity and chronic inflammation. The effects of endurance exercise in modulating these outcomes in insulin-resistant obese adults remain unclear. We investigated the effect of endurance exercise on markers of oxidative damage (4-hydroxy-2-nonenal (4-HNE), protein carbonyls (PCs)) and antioxidant enzymes (superoxide dismutase (SOD), catalase) in skeletal muscle; urinary markers of oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane); and plasma cytokines (C-reactive protein (CRP), interleukin-6 (IL-6), leptin, adiponectin). Methods: Age- and fitness-matched sedentary obese and lean men (n=9 per group) underwent 3 months of moderate-intensity endurance cycling training with a vastus lateralis biopsy, 24-h urine sample and venous blood samples taken before and after the intervention. Results: Obese subjects had increased levels of oxidative damage: 4-HNE (+37% P⩽0.03) and PC (+63% P⩽0.02); evidence of increased adaptive response to oxidative stress because of elevated levels of copper/zinc SOD (Cu/ZnSOD) protein content (+84% P⩽0.01); increased markers of inflammation: CRP (+737% P⩽0.0001) and IL-6 (+85% P⩽0.03), and these correlated with increased markers of obesity; and increased leptin (+262% P⩽0.0001) with lower adiponectin (−27% P⩽0.01) levels vs lean controls. Training reduced 4-HNE (−10% P⩽0.04), PC (−21% P⩽0.05), 8-isoprostane (−26% P⩽0.02) and leptin levels (−33% P⩽0.01); had a tendency to decrease IL-6 levels (−21% P=0.07) and IR (−17% P=0.10); and increased manganese SOD (MnSOD) levels (+47% P⩽0.01). Conclusion: Endurance exercise reduced skeletal muscle-specific and systemic oxidative damage while improving IR and cytokine profile associated with obesity, independent of weight loss. Hence, exercise is a useful therapeutic modality to reduce risk factors associated with the pathogenesis of IR in obesity. PMID:24042701

The forgotten face of regular physical exercise: a 'natural' anti-atherogenic activity.

PubMed

Szostak, Justyna; Laurant, Pascal

2011-08-01

Humans are not programmed to be inactive. The combination of both accelerated sedentary lifestyle and constant food availability disturbs ancient metabolic processes leading to excessive storage of energy in tissue, dyslipidaemia and insulin resistance. As a consequence, the prevalence of Type 2 diabetes, obesity and the metabolic syndrome has increased significantly over the last 30 years. A low level of physical activity and decreased daily energy expenditure contribute to the increased risk of cardiovascular morbidity and mortality following atherosclerotic vascular damage. Physical inactivity leads to the accumulation of visceral fat and consequently the activation of the oxidative stress/inflammation cascade, which promotes the development of atherosclerosis. Considering physical activity as a 'natural' programmed state, it is assumed that it possesses atheroprotective properties. Exercise prevents plaque development and induces the regression of coronary stenosis. Furthermore, experimental studies have revealed that exercise prevents the conversion of plaques into a vulnerable phenotype, thus preventing the appearance of fatal lesions. Exercise promotes atheroprotection possibly by reducing or preventing oxidative stress and inflammation through at least two distinct pathways. Exercise, through laminar shear stress activation, down-regulates endothelial AT1R (angiotensin II type 1 receptor) expression, leading to decreases in NADPH oxidase activity and superoxide anion production, which in turn decreases ROS (reactive oxygen species) generation, and preserves endothelial NO bioavailability and its protective anti-atherogenic effects. Contracting skeletal muscle now emerges as a new organ that releases anti-inflammatory cytokines, such as IL-6 (interleukin-6). IL-6 inhibits TNF-α (tumour necrosis factor-α) production in adipose tissue and macrophages. The down-regulation of TNF-α induced by skeletal-muscle-derived IL-6 may also participate in mediating the atheroprotective effect of physical activity.

Weight loss reduces breast ductal fluid estrogens in obese postmenopausal women: a single arm intervention pilot study.

PubMed

Carpenter, Catherine L; Duvall, Karen; Jardack, Patricia; Li, Luyi; Henning, Susanne M; Li, Zhaoping; Heber, David

2012-12-05

Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women. We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2) postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass); exercise fitness (maximum oxygen consumption (VO2Max); 1-repetition strength maximum); and breast ductal lavage. Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop), VO2Max (+36% increase) and strength improvement (+26%). Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline), estrone sulfate (-10%), estradiol (-25%), and Il-6 (-33%). Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

Improved Insulin Sensitivity After Exercise Training is Linked to Reduced Plasma C14:0 Ceramide in Obesity and Type 2 Diabetes

PubMed Central

Kasumov, Takhar; Solomon, Thomas P.J.; Hwang, Calvin; Huang, Hazel; Haus, Jacob M.; Zhang, Renliang; Kirwan, John P.

2015-01-01

Objective To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Methods Twenty-four adults with obesity and normal glucose tolerance (NGT, n=14), or diabetes (n=10) were studied before and after a 12-week supervised exercise-training program (5 d/wk, 1 hr/d, 80–85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m2/min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0 and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Results Plasma ceramides were similar for the obese NGT and subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity, and increased peripheral insulin sensitivity in both groups (P<0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P<0.05). Decreases in total (r=-0.51, P=0.02) and C14:0 (r=-0.56, P=0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Conclusion Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. PMID:25966363

Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes.

PubMed

Kasumov, Takhar; Solomon, Thomas P J; Hwang, Calvin; Huang, Hazel; Haus, Jacob M; Zhang, Renliang; Kirwan, John P

2015-07-01

To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Twenty-four adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n = 10) were studied before and after a 12-week supervised exercise-training program (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups (P < 0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P < 0.05). Decreases in total (r = -0.51, P = 0.02) and C14:0 (r = -0.56, P = 0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. © 2015 The Obesity Society.

Adipose Tissue Plasticity During Catch-Up Fat Driven by Thrifty Metabolism

PubMed Central

Summermatter, Serge; Marcelino, Helena; Arsenijevic, Denis; Buchala, Antony; Aprikian, Olivier; Assimacopoulos-Jeannet, Françoise; Seydoux, Josiane; Montani, Jean-Pierre; Solinas, Giovanni; Dulloo, Abdul G.

2009-01-01

OBJECTIVE Catch-up growth, a risk factor for later type 2 diabetes, is characterized by hyperinsulinemia, accelerated body-fat recovery (catch-up fat), and enhanced glucose utilization in adipose tissue. Our objective was to characterize the determinants of enhanced glucose utilization in adipose tissue during catch-up fat. RESEARCH DESIGN AND METHODS White adipose tissue morphometry, lipogenic capacity, fatty acid composition, insulin signaling, in vivo glucose homeostasis, and insulinemic response to glucose were assessed in a rat model of semistarvation-refeeding. This model is characterized by glucose redistribution from skeletal muscle to adipose tissue during catch-up fat that results solely from suppressed thermogenesis (i.e., without hyperphagia). RESULTS Adipose tissue recovery during the dynamic phase of catch-up fat is accompanied by increased adipocyte number with smaller diameter, increased expression of genes for adipogenesis and de novo lipogenesis, increased fatty acid synthase activity, increased proportion of saturated fatty acids in triglyceride (storage) fraction but not in phospholipid (membrane) fraction, and no impairment in insulin signaling. Furthermore, it is shown that hyperinsulinemia and enhanced adipose tissue de novo lipogenesis occur concomitantly and are very early events in catch-up fat. CONCLUSIONS These findings suggest that increased adipose tissue insulin stimulation and consequential increase in intracellular glucose flux play an important role in initiating catch-up fat. Once activated, the machinery for lipogenesis and adipogenesis contribute to sustain an increased insulin-stimulated glucose flux toward fat storage. Such adipose tissue plasticity could play an active role in the thrifty metabolism that underlies glucose redistribution from skeletal muscle to adipose tissue. PMID:19602538

Microbiota depletion promotes browning of white adipose tissue and reduces obesity

PubMed Central

Chevalier, Claire; Stojanović, Ozren; Colin, Didier J.; Stevanović, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothée; Germain, Stéphane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko

2015-01-01

Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity1. In response to cold or exercise brown fat cells also emerge in the white adipose tissue (named beige cells), a process known as browning2,3,4. Here, we show that the development of functional beige fat is promoted by microbiota depletion either by antibiotic treatment or in germ-free mice within the inguinal subcutaneous and perigonadal visceral adipose tissues (ingSAT and pgVAT, respectively). This leads to improved glucose tolerance, insulin sensitivity and decreased white fat and adipocyte size in lean mice and obese leptin-deficient (ob/ob) and high fat diet (HFD)-fed mice. These metabolic improvements are mediated by eosinophil infiltration and enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by suppression of the type 2 signaling and are reversed by recolonization of the antibiotic-treated, or the germ-free mice with microbes. These results provide insight into microbiota-fat signaling axis and beige fat development in health and metabolic disease. PMID:26569380

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management.

PubMed

Zhang, Yingmei; Ren, Jun

2016-05-01

Uncorrected obesity has been associated with cardiac hypertrophy and contractile dysfunction. Several mechanisms for this cardiomyopathy have been identified, including oxidative stress, autophagy, adrenergic and renin-angiotensin aldosterone overflow. Another process that may regulate effects of obesity is epigenetics, which refers to the heritable alterations in gene expression or cellular phenotype that are not encoded on the DNA sequence. Advances in epigenome profiling have greatly improved the understanding of the epigenome in obesity, where environmental exposures during early life result in an increased health risk later on in life. Several mechanisms, including histone modification, DNA methylation and non-coding RNAs, have been reported in obesity and can cause transcriptional suppression or activation, depending on the location within the gene, contributing to obesity-induced complications. Through epigenetic modifications, the fetus may be prone to detrimental insults, leading to cardiac sequelae later in life. Important links between epigenetics and obesity include nutrition, exercise, adiposity, inflammation, insulin sensitivity and hepatic steatosis. Genome-wide studies have identified altered DNA methylation patterns in pancreatic islets, skeletal muscle and adipose tissues from obese subjects compared with non-obese controls. In addition, aging and intrauterine environment are associated with differential DNA methylation. Given the intense research on the molecular mechanisms of the etiology of obesity and its complications, this review will provide insights into the current understanding of epigenetics and pharmacological and non-pharmacological (such as exercise) interventions targeting epigenetics as they relate to treatment of obesity and its complications. Particular focus will be on DNA methylation, histone modification and non-coding RNAs. Copyright © 2016 Elsevier Inc. All rights reserved.

Browning of White Fat: Novel Insight Into Factors, Mechanisms, and Therapeutics.

PubMed

Jeremic, Nevena; Chaturvedi, Pankaj; Tyagi, Suresh C

2017-01-01

What is more interesting about brown adipose tissue (BAT) is its ability to provide thermogenesis, protection against obesity by clearing triglycerides, releasing batokines, and mitigating insulin resistance. White adipose tissue (WAT) on the other hand stores excess energy and secretes some endocrine factors like leptin for regulating satiety. For the last decade there has been an increasing interest in the browning of fat keeping in view its beneficial effects on metabolic disorders and protection in the form of perivascular fat. Obesity is one such metabolic disorder that leads to significant morbidity and mortality from obesity-related disorders such as type 2 diabetes mellitus (T2D) and cardiovascular disease risk. Browning of white fat paves the way to restrict obesity and obesity related disorders. Although exercise has been the most common factor for fat browning; however, there are other factors that involve: (1) beta aminoisobutyric acid (BAIBA); (2) gamma amino butyric acid (GABA); (3) PPARɣ agonists; (4) JAK inhibition; and (5) IRISIN. In this review, we propose two novel factors musclin and TFAM for fat browning. Musclin a myokine released from muscles during exercise activates PPARɣ which induces browning of WAT that has beneficial metabolic and cardiac effects. TFAM is a transcription factor that induces mitochondrial biogenesis. Since BAT is rich in mitochondria, higher expression of TFAM in WAT or TFAM treatment in WAT cells can induce browning of WAT. We propose that fat browning can be used as a therapeutic tool for metabolic disorders and cardiovascular diseases. J. Cell. Physiol. 232: 61-68, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of interval exercise training programme on the indices of adiposity and biomarker of inflammation in hypertension: a randomised controlled trial.

PubMed

Lamina, S; Okoye, C G; Hanif, S M

2014-06-01

Hypertension remains a significant risk factor in cardiovascular morbidity and mortality. The purpose of the present study was to investigate the effects of 8 weeks interval training programme on blood pressure, aerobic capacity (VO max), indices of adiposity and marker of inflammation in black African men with essential hypertension. Two hundred and forty five (245) male subjects with stage 1 and 2 (systolic blood pressure [SBP] between 140-179 & diastolic blood pressure [DBP] between 90-109 mmHg) essential hypertension were age matched and grouped into experimental and control groups. The experimental (n=140; 58.90 ± 7.35 years) group involved in an 8 weeks interval training (60-79% HRmax) programme of between 45 and 60 minutes, while age-matched control hypertensive (n=105; 58.27±6.24 years) group remain sedentary during this period. All subjects in both groups were on antihypertensive drugs throughout the study period. Cardiovascular parameters (SBP, DBP) & VO max and percent body fat [%BF], waist to hip ratio [WHR] and C-reactive protein [CRP] were assessed. Independent t-test and Pearson correlation test were used in data analysis. Findings of the study revealed significant decreased effects of interval training programme on SBP, DBP, %BF, WHR and CRP and significant increased effect on VO max at p< 0.05. Also, changes in CRP as a result of exercise training significantly and positively correlated with changes in SBP, DBP, %BF, WHR, CRP and negatively correlated with VO max at p< 0.05.

Circulating leptin concentrations do not distinguish menstrual status in exercising women.

PubMed

Corr, M; De Souza, M J; Toombs, R J; Williams, N I

2011-03-01

Low concentrations of leptin secondary to low body fat or other modulators are thought to be a key signal whereby an energy deficit suppresses the reproductive axis in exercising women resulting in functional hypothalamic amenorrhea (FHA). The purpose of this study was to first examine leptin concentrations in exercising women with and without FHA to address whether there is a threshold concentration of leptin below which reproductive function is suppressed. Secondly, we examined the role of adiposity and other possible modulators of leptin to ascertain whether leptin regulation differs depending on reproductive status. This study assessed 50 exercising, premenopausal women (aged 18-30 years) over the course of one menstrual cycle (eumenorrheic women) or one 28-day monitoring period (amenorrheic women). Quantification of daily urinary ovarian steroids and menstrual history were used to determine menstrual status. Body composition was assessed using dual energy X-ray absorptiometry, and leptin was determined by enzyme-linked immunoassay. Key modulators of leptin such as serum insulin concentration, carbohydrate intake, glucose availability, indirect indices of sympathetic nervous activity and other factors were assessed using linear regression. Percentage body fat (%BF) (21.0 ± 1.0 versus 26.8 ± 0.7%; P < 0.001) and leptin concentration (4.8 ± 0.8 versus 9.6 ± 0.9 ng/ml; P < 0.001) were lower in the exercising women with amenorrhea (ExAmen; n = 24) compared with the exercising ovulatory women (ExOvul; n = 26). However, the ranges in leptin were similar for each group (ExAmen: 0.30-16.98 ng/ml; ExOvul: 2.57-18.28 ng/ml), and after adjusting for adiposity the difference in leptin concentration was no longer significant. Significant predictors of log leptin in ExAmen included %BF (β = 0.826, P < 0.001), log insulin (β = 0.308, P = 0.012) and log glycerol (β = 0.258, P = 0.030), but in ExOvul only %BF predicted leptin. CONCLUSIONS These data suggest that leptin concentrations per se are not associated with FHA in exercising women, but the modulation of leptin concentrations may differ depending on reproductive status.

Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with dynamic changes in adipose tissue and skeletal muscle.

PubMed

Yamashita, Yuri; Nakada, Satoshi; Yoshihara, Toshinori; Nara, Takeshi; Furuya, Norihiko; Miida, Takashi; Hattori, Nobutaka; Arikawa-Hirasawa, Eri

2018-05-17

Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2 -/- -Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2 -/- -Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation. In addition, the Hspg2 -/- -Tg mice demonstrated increased insulin sensitivity. Molecular analysis revealed the significantly relatively increased amount of the muscle fiber type IIA (X) isoform and a larger quantity of mitochondria in the skeletal muscle of Hspg2 -/- -Tg mice. Furthermore, the perlecan-deficient skeletal muscle also had elevated levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) protein. PGC1α expression is activated by exercise, and induces mitochondrial biosynthesis. Thus, perlecan may act as a mechano-regulator of catabolism of both lipids and glucose by shifting the muscle fiber composition to oxidative fibers. Our data suggest that downregulation of perlecan is a promising strategy to control metabolic syndrome.

Effect of exercise on serum vitamin D and tissue vitamin D receptors in experimentally induced type 2 Diabetes Mellitus.

PubMed

Aly, Yosria E; Abdou, Azza S; Rashad, Mona M; Nassef, Menatallah M

2016-09-01

This work aimed to study the effect of swimming exercise on serum vitamin D level and tissue vitamin D receptors in experimentally induced type 2 Diabetes Mellitus. Sixty adult male rats were divided into control and diabetic groups. Each was further subdivided into sedentary and exercised subgroups. Diabetes Mellitus was induced by a single intraperitoneal dose of streptozotocin (50 mg/kg) dissolved in cold 0.01 M citrate buffer (pH 4.5). The exercised subgroups underwent swimming for 60 min, 5 times a week for 4 weeks. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids, vitamin D and tissue Vitamin D receptors (VDR) were evaluated. Significant increase in serum glucose, insulin, HOMA-IR, cholesterol, triglycerides, and low density lipoprotein (LDL) levels in sedentary diabetic rats was detected. On the other hand, high density lipoprotein (HDL), free fatty acids, serum vitamin D and pancreatic, adipose, and muscular VDR showed a significant decrease in the same group. It is evident that all these parameters were reversed by swimming exercise indicating its beneficial role in type 2 Diabetes. In diabetic groups; serum vitamin D was found to be correlated negatively with serum glucose, insulin, HOMA, cholesterol, triglycerides, and LDL and positively correlated with HDL and tissue VDR. In conclusion, Disturbed vitamin D is associated with metabolic impairments in sedentary diabetic rats. Moderate swimming exercise is beneficial in improving these consequences through modulation of vitamin D status. Future studies could be designed to investigate the effect of the combination of vitamin D intake with exercise in diabetic patients.

Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes.

PubMed

Kruse, Rikke; Vienberg, Sara G; Vind, Birgitte F; Andersen, Birgitte; Højlund, Kurt

2017-10-01

Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established. The effects of insulin during euglycaemic-hyperinsulinaemic clamps and 10 week endurance training on serum FGF21 were examined in individuals with type 2 diabetes and in glucose tolerant overweight/obese and lean individuals. Gene expression of FGF21, its receptors and target genes in muscle and WAT biopsies was evaluated by quantitative real-time PCR (qPCR). Insulin increased serum and muscle FGF21 independent of overweight/obesity or type 2 diabetes, and there were no effects associated with exercise training. The insulin-induced increases in serum FGF21 and muscle FGF21 expression correlated tightly (p < 0.001). In WAT, overweight/obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes. Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure adequate expression of most FGF21 target genes in WAT.

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country.

PubMed

Backer, Vibeke; Baines, Katherine J; Powell, Heather; Porsbjerg, Celeste; Gibson, Peter G

2016-02-01

An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet. To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p < 0.0001) and associated with increased adipose tissue IL-6 gene expression and increased BMI. There was no association between asthma and adipose tissue mast cell gene expression. Pro-inflammatory gene expression (IL-6, IL-1β) was higher in those living in Denmark, and with increasing BMI and dietary changes. The anti-inflammatory (M2) macrophage marker, CD163, was higher in Greenland-dwelling Inuit (p < 0.01). No association was found between gene expression of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Obesity, Exercise and Orthopedic Disease.

PubMed

Frye, Christopher W; Shmalberg, Justin W; Wakshlag, Joseph J

2016-09-01

Osteoarthritis is common among aging canine and feline patients. The incidence and severity of clinical lameness are closely correlated to body condition in overweight and obese patients. Excessive adiposity may result in incongruous and excessive mechanical loading that worsens clinical signs in affected patients. Data suggest a potential link between adipokines, obesity-related inflammation, and a worsening of the underlying pathology. Similarly, abnormal physical stress and generalized systemic inflammation propagated by obesity contribute to neurologic signs associated with intervertebral disc disease. Weight loss and exercise are critical to ameliorating the pain and impaired mobility of affected animals. Copyright © 2016 Elsevier Inc. All rights reserved.

The TRPC1 CA2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes

USDA-ARS?s Scientific Manuscript database

The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+ permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle, making it a likely candidate for the regulation of cellular energy metabolism. However, the exact role ...

Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

ClinicalTrials.gov

2018-05-01

Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Gut Microbiota: Modulation of Host Physiology in Obesity

PubMed Central

Allen, Jacob M.; Mailing, Lucy J.; Kashyap, Purna C.; Woods, Jeffrey A.

2016-01-01

Many factors are involved in weight gain and metabolic disturbances associated with obesity. The gut microbiota has been of particular interest in recent years, since both human and animal studies have increased our understanding of the delicate symbiosis between the trillions of microbes that reside in the GI tract and the host. It has been suggested that disruption of this mutual tolerance may play a significant role in modulating host physiology during obesity. Environmental influences such as diet, exercise, and early life exposures can significantly impact the composition of the microbiota, and this dysbiosis can in turn lead to increased host adiposity via a number of different mechanisms. The ability of the microbiota to regulate host fat deposition, metabolism, and immune function makes it an attractive target for achieving sustained weight loss. PMID:27511459

Supervised exercise training counterbalances the adverse effects of insulin therapy in overweight/obese subjects with type 2 diabetes.

PubMed

Balducci, Stefano; Zanuso, Silvano; Cardelli, Patrizia; Salerno, Gerardo; Fallucca, Sara; Nicolucci, Antonio; Pugliese, Giuseppe

2012-01-01

To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary, overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study (IDES). The study randomized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling (EXE) or to counseling alone (CON) for 12 months. Clinical and laboratory parameters were assessed at baseline and at the end of the study. The volume of physical activity was significantly higher in the EXE versus the CON group. Values for hemoglobin A(1c), BMI, waist circumference, high-sensitivity C-reactive protein, blood pressure, LDL cholesterol, and the coronary heart disease risk score were significantly reduced only in the EXE group. No major adverse events were observed. In insulin-treated subjects with type 2 diabetes, supervised exercise is safe and effective in improving glycemic control and markers of adiposity and inflammation, thus counterbalancing the adverse effects of insulin on these parameters.

Phytochemicals and their impact on adipose tissue inflammation and diabetes.

PubMed

Leiherer, Andreas; Mündlein, Axel; Drexel, Heinz

2013-01-01

Type 2 diabetes mellitus is an inflammatory disease and the mechanisms that underlie this disease, although still incompletely understood, take place in the adipose tissue of obese subjects. Concurrently, the prevalence of obesity caused by Western diet's excessive energy intake and the lack of exercise escalates, and is believed to be causative for the chronic inflammatory state in adipose tissue. Overnutrition itself as an overload of energy may induce the adipocytes to secrete chemokines activating and attracting immune cells to adipose tissue. But also inflammation-mediating food ingredients like saturated fatty acids are believed to directly initiate the inflammatory cascade. In addition, hypoxia in adipose tissue as a direct consequence of obesity, and its effect on gene expression in adipocytes and surrounding cells in fat tissue of obese subjects appears to play a central role in this inflammatory response too. In contrast, revisiting diet all over the world, there are also some natural food products and beverages which are associated with curative effects on human health. Several natural compounds known as spices such as curcumin, capsaicin, and gingerol, or secondary plant metabolites catechin, resveratrol, genistein, and quercetin have been reported to provide an improved health status to their consumers, especially with regard to diabetes, and therefore have been investigated for their anti-inflammatory effect. In this review, we will give an overview about these phytochemicals and their role to interfere with inflammatory cascades in adipose tissue and their potential for fighting against inflammatory diseases like diabetes as investigated in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Meal frequency of pre-exercise carbohydrate feedings.

PubMed

Chryssanthopoulos, C; Petridou, A; Maridaki, M; Mougios, V

2008-04-01

This study compared the effect of single and multiple carbohydrate feedings before exercise on biochemical and physiological responses during exercise. Eight males performed 3 runs for 1 h at 70 % VO(2max) after consuming a meal containing 2.5 g carbohydrate per kg body mass in a single dose 3 h before exercise (SF), the same meal in 5 equal doses at 3, 2.5, 2, 1.5, and 1 h before exercise (MF), or a liquid placebo 3 h before exercise (P). RER and carbohydrate oxidation rates were higher in SF and MF compared to P trials, but there was no difference between SF and MF trials. Pre-exercise insulin was 2.0- and 3.4- fold higher in SF and MF, respectively, compared to P, and 1.7-fold higher in MF compared to SF. Glycerol and NEFA were higher in P compared to SF and MF trials before and at the end of exercise. In conclusion, a carbohydrate meal containing 2.5 g . kg(-1) ingested in doses over 3 h before running produced higher hyperinsulinemia pre-exercise than that produced when the meal was consumed in a single dose. Nevertheless, estimated carbohydrate utilization and adipose tissue lipolysis during exercise after multiple feedings seemed to be as high as after a single feeding.

Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial1234

PubMed Central

Nicklas, Barbara J; Wang, Xuewen; You, Tongjian; Lyles, Mary F; Demons, Jamehl; Easter, Linda; Berry, Michael J; Lenchik, Leon; Carr, J Jeffrey

2009-01-01

Background: Exercise intensity may affect the selective loss of abdominal adipose tissue. Objective: This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. Design: This was a randomized trial in 112 overweight and obese [body mass index (in kg/m2): 25–40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (≈400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45–50% (moderate-intensity) or 70–75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. Results: Average weight loss for the 95 women who completed the study was 12.1 kg (±4.5 kg) and was not significantly different across groups. Maximal oxygen uptake (O2max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (≈25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O2max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. Conclusion: With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was registered at clinicaltrials.gov as NCT00664729. PMID:19211823

Lifestyle intervention to improve quality of life and prevent weight gain after renal transplantation: Design of the Active Care after Transplantation (ACT) randomized controlled trial.

PubMed

Klaassen, Gerald; Zelle, Dorien M; Navis, Gerjan J; Dijkema, Desie; Bemelman, Frederike J; Bakker, Stephan J L; Corpeleijn, Eva

2017-09-15

Low physical activity and reduced physical functioning are common after renal transplantation, resulting in a reduced quality of life. Another common post-transplantation complication is poor cardio-metabolic health, which plays a main role in long-term outcomes in renal transplant recipients (RTR). It is increasingly recognized that weight gain in the first year after transplantation, especially an increase in fat mass, is a highly common contributor to cardio-metabolic risk. The aim of this study is to compare the outcomes of usual care to the effects of exercise alone, and exercise combined with dietary counseling, on physical functioning, quality of life and post-transplantation weight gain in RTR. The Active Care after Transplantation study is a multicenter randomized controlled trial with three arms in which RTR from 3 Dutch hospitals are randomized within the first year after transplantation to usual care, to exercise intervention (3 months supervised exercise 2 times per week followed by 12 months active follow-up), or to an exercise + diet intervention, consisting of the exercise training with additional dietary counseling (12 sessions over 15 months by a renal dietician). In total, 219 participants (73 per group) will be recruited. The primary outcome is the subdomain physical functioning of quality of life, (SF-36 PF). Secondary outcomes include other evaluations of quality of life (SF-36, KDQOL-SF, EQ-5D), objective measures of physical functioning (aerobic capacity and muscle strength), level of physical activity, gain in adiposity (body fat percentage by bio-electrical impedance assessment, BMI, waist circumference), and cardiometabolic risk factors (blood pressure, lipids, glucose metabolism). Furthermore, data on renal function, medical history, medication, psychological factors (motivation, kinesiophobia, coping style), nutrition knowledge, nutrition intake, nutrition status, fatigue, work participation, process evaluation and cost-effectiveness are collected. Evidence on the effectiveness of an exercise intervention, or an exercise + diet intervention on physical functioning, weight gain and cardiometabolic health in RTR is currently lacking. The outcomes of the present study may help to guide future evidence-based lifestyle care after renal transplantation. Number: NCT01047410 .

Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods

PubMed Central

2014-01-01

Background Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments. Methods/Design This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. Discussion This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform intervention programs that will optimally improve physiological and psychosocial health during cancer survivorship, and that are ultimately aimed at improving prognosis. Trial registration NCT01140282; Registration: June 10, 2010 PMID:24708832

Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via toll-like receptor-2-mediated pathways

USDA-ARS?s Scientific Manuscript database

Increases in adipose tissue weight positively correlates with increased circulating inflammatory cytokines such as interleukin-6 (IL-6). We previously have shown that adipose stem cell produce significantly higher levels of IL-6 when compared to other cell types in the adipose tissue in genetically ...

Assessing the effect of a high-fat diet on rodents' adipose tissue using Brillouin and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Troyanova-Wood, Maria; Gobbell, Cassidy; Meng, Zhaokai; Yakovlev, Vladislav V.

2016-03-01

The purpose of this study is to evaluate the effect of a high-lipid diet on elasticity of adipose tissue. We employed dual Raman/Brillouin microspectroscopy to analyze brown and white adipose tissues obtained from adult rats. The rats were divided into two groups, one of which received a high-fat feed, while the other served as a control. We hypothesized that the changes in the elasticity of adipose tissues between the two groups can be successfully assessed using Brillouin spectroscopy. We found that the brown adipose tissue possessed a lesser Brillouin shift than the white adipose within each group and that the elastic modulus of both adipose tissues increases in the high-fat diet group. The Raman spectra provided supplementary chemical information and indicated an increase in the lipid-to-protein ratio in the brown adipose, but not in the white adipose.

MKK6 controls T3-mediated browning of white adipose tissue.

PubMed

Matesanz, Nuria; Bernardo, Edgar; Acín-Pérez, Rebeca; Manieri, Elisa; Pérez-Sieira, Sonia; Hernández-Cosido, Lourdes; Montalvo-Romeral, Valle; Mora, Alfonso; Rodríguez, Elena; Leiva-Vega, Luis; Lechuga-Vieco, Ana Victoria; Ruiz-Cabello, Jesús; Torres, Jorge L; Crespo-Ruiz, Maria; Centeno, Francisco; Álvarez, Clara V; Marcos, Miguel; Enríquez, Jose Antonio; Nogueiras, Ruben; Sabio, Guadalupe

2017-10-11

Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity.Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.

Dietary Weight Loss and Exercise Effects on Serum Biomarkers of Angiogenesis in Overweight Postmenopausal Women: A Randomized Controlled Trial.

PubMed

Duggan, Catherine; Tapsoba, Jean de Dieu; Wang, Ching-Yun; McTiernan, Anne

2016-07-15

Obese and sedentary persons have an increased risk for cancer, but underlying mechanisms are poorly understood. Angiogenesis is common to adipose tissue formation and remodeling, and to tumor vascularization. A total of 439 overweight/obese, healthy, postmenopausal women [body mass index (BMI) > 25 kg/m(2)] ages 50-75 years, recruited between 2005 and 2008 were randomized to a 4-arm 12-month randomized controlled trial, comparing a caloric restriction diet arm (goal: 10% weight loss, N = 118), aerobic exercise arm (225 minutes/week of moderate-to-vigorous activity, N = 117), a combined diet + exercise arm (N = 117), or control (N = 87) on circulating levels of angiogenic biomarkers. VEGF, plasminogen activator inhibitor-1 (PAI-1), and pigment epithelium-derived factor (PEDF) were measured by immunoassay at baseline and 12 months. Changes were compared using generalized estimating equations, adjusting for baseline BMI, age, and race/ethnicity. Participants randomized to the diet + exercise arms had statistically significantly greater reductions in PAI-1 at 12 months compared with controls (-19.3% vs. +3.48%, respectively, P < 0.0001). Participants randomized to the diet and diet + exercise arms had statistically significantly greater reductions in PEDF (-9.20%, -9.90%, respectively, both P < 0.0001) and VEGF (-8.25%, P = 0.0005; -9.98%, P < 0.0001, respectively) compared with controls. There were no differences in any of the analytes in participants randomized to the exercise arm compared with controls. Increasing weight loss was statistically significantly associated with linear trends of greater reductions in PAI-1, PEDF, and VEGF. Weight loss is significantly associated with reduced circulating VEGF, PEDF, and PAI-1, and could provide incentive for reducing weight as a cancer prevention method in overweight and obese individuals. Cancer Res; 76(14); 4226-35. ©2016 AACR. ©2016 American Association for Cancer Research.

Characterization of the swine adipocyte A1 adenosine receptor using an optimized assay system.

PubMed

Dong, Q; Schuchman, J; Carey, G B

1994-07-01

The radioligand binding assay of A1 adenosine receptors in adipocyte crude plasma membrane from Yucatan miniature swine was optimized by evaluating 17 factors involved in the assay. Significant effects of CHAPS, adenosine deaminase, EDTA, pre-rinsing glass fiber filters and pH were found for the binding measurements. Using the optimized procedure, [3H]8-cyclopentyl-1,3-dipropylxanthine, ([3H]-DPCPX) binding to A1 adenosine receptors in swine subcutaneous adipocyte crude plasma membrane was measured; Bmax and Kd values were 479 +/- 77 fmol/mg protein and 0.87 +/- 0.10 nM, respectively. Values for mesenteric adipose tissue from sedentary swine and subcutaneous adipose tissue from exercise-trained swine were also measured.

Effects of adipose tissue distribution on maximum lipid oxidation rate during exercise in normal-weight women.

PubMed

Isacco, L; Thivel, D; Duclos, M; Aucouturier, J; Boisseau, N

2014-06-01

Fat mass localization affects lipid metabolism differently at rest and during exercise in overweight and normal-weight subjects. The aim of this study was to investigate the impact of a low vs high ratio of abdominal to lower-body fat mass (index of adipose tissue distribution) on the exercise intensity (Lipox(max)) that elicits the maximum lipid oxidation rate in normal-weight women. Twenty-one normal-weight women (22.0 ± 0.6 years, 22.3 ± 0.1 kg.m(-2)) were separated into two groups of either a low or high abdominal to lower-body fat mass ratio [L-A/LB (n = 11) or H-A/LB (n = 10), respectively]. Lipox(max) and maximum lipid oxidation rate (MLOR) were determined during a submaximum incremental exercise test. Abdominal and lower-body fat mass were determined from DXA scans. The two groups did not differ in aerobic fitness, total fat mass, or total and localized fat-free mass. Lipox(max) and MLOR were significantly lower in H-A/LB vs L-A/LB women (43 ± 3% VO(2max) vs 54 ± 4% VO(2max), and 4.8 ± 0.6 mg min(-1)kg FFM(-1)vs 8.4 ± 0.9 mg min(-1)kg FFM(-1), respectively; P < 0.001). Total and abdominal fat mass measurements were negatively associated with Lipox(max) (r = -0.57 and r = -0.64, respectively; P < 0.01) and MLOR [r = -0.63 (P < 0.01) and r = -0.76 (P < 0.001), respectively]. These findings indicate that, in normal-weight women, a predominantly abdominal fat mass distribution compared with a predominantly peripheral fat mass distribution is associated with a lower capacity to maximize lipid oxidation during exercise, as evidenced by their lower Lipox(max) and MLOR. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese post-menopausal women

PubMed Central

Foster-Schubert, KE; Alfano, CM; Duggan, CR; Xiao, L; Campbell, KL; Kong, A; Bain, C; Wang, CY; Blackburn, G; McTiernan, A

2012-01-01

Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet towards whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45 min aerobic exercise 5 d/wk. Participants were predominantly non-Hispanic Whites (85%) with a mean age of 58.0±5.0 years, a mean BMI of 30.9±4.0 kg/m2 and an average of 47.8±4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants’ intervention assignment. 399 women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was −8.5% for the D group (P<0.0001 vs. C), −2.4% for the E group (P=0.03 vs. C), and −10.8% for the D+E group (P<0.0001 vs. C), while the C group experienced a non-significant −0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention. PMID:21494229

Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese postmenopausal women.

PubMed

Foster-Schubert, Karen E; Alfano, Catherine M; Duggan, Catherine R; Xiao, Liren; Campbell, Kristin L; Kong, Angela; Bain, Carolyn E; Wang, Ching-Yun; Blackburn, George L; McTiernan, Anne

2012-08-01

Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet toward whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week. Participants were predominantly non-Hispanic whites (85%) with a mean age of 58.0 ± 5.0 years, a mean BMI of 30.9 ± 4.0 kg/m(2) and an average of 47.8 ± 4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants' intervention assignment. Three hundred and ninety nine women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was -8.5% for the D group (P < 0.0001 vs. C), -2.4% for the E group (P = 0.03 vs. C), and -10.8% for the D+E group (P < 0.0001 vs. C), whereas the C group experienced a nonsignificant -0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle-change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.

Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity.

PubMed

Park, S; Park, H-L; Lee, S-Y; Nam, J-H

2016-03-01

Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied. Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO. In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection. These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.

PubMed

Vigelsø, A; Gram, M; Dybboe, R; Kuhlman, A B; Prats, C; Greenhaff, P L; Constantin-Teodosiu, D; Birk, J B; Wojtaszewski, J F P; Dela, F; Helge, J W

2016-04-15

This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate-intensity exercise. Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two-legged dynamic knee-extensor moderate-intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise. Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise. Using a combined whole-leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms. Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate-intensity exercise in young (n = 17; 23 ± 1 years old) and older men (n = 15; 68 ± 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two-legged isolated knee-extensor exercise at 20 ± 1 W (∼50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl-CoA carboxylase 2 and AMP-activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane-associated fatty acid binding protein and AMPKγ3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole-leg and molecular differences in fatty acid mobilization could explain the age- and immobilization-induced IMTG accumulation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate‐intensity exercise in human skeletal muscle

PubMed Central

Gram, M.; Dybboe, R.; Kuhlman, A. B.; Prats, C.; Greenhaff, P. L.; Constantin‐Teodosiu, D.; Birk, J. B.; Wojtaszewski, J. F. P.; Dela, F.; Helge, J. W.

2016-01-01

Key points This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate‐intensity exercise.Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two‐legged dynamic knee‐extensor moderate‐intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise.Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise.Using a combined whole‐leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms. Abstract Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate‐intensity exercise in young (n = 17; 23 ± 1 years old) and older men (n = 15; 68 ± 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two‐legged isolated knee‐extensor exercise at 20 ± 1 W (∼50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl‐CoA carboxylase 2 and AMP‐activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane‐associated fatty acid binding protein and AMPKγ3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole‐leg and molecular differences in fatty acid mobilization could explain the age‐ and immobilization‐induced IMTG accumulation. PMID:26801521

Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

PubMed Central

Sallam, Nada

2016-01-01

Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential. PMID:26823952

Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases.

PubMed

Sallam, Nada; Laher, Ismail

2016-01-01

Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential.

Acute Hypercortisolemia Exerts Depot-Specific Effects on Abdominal and Femoral Adipose Tissue Function

PubMed Central

O’Reilly, Michael W.; Bujalska, Iwona J.; Tomlinson, Jeremy W.; Arlt, Wiebke

2017-01-01

Context: Glucocorticoids have pleiotropic metabolic functions, and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear. Objective: To provide an in vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration. Design and Outcome Measures: Nine healthy male volunteers were studied on two occasions, after a hydrocortisone infusion (0.2 mg/kg/min for 14 hours) and a saline infusion, respectively, given in randomized double-blind order. The subjects were studied in the fasting state and after a 75-g glucose drink with an in vivo assessment of femoral adipose tissue blood flow (ATBF) using radioactive xenon washout and of lipolysis and glucose uptake using the arteriovenous difference technique. In a separate study (same infusion design), eight additional healthy male subjects underwent assessment of fasting abdominal ATBF and lipolysis only. Lipolysis was assessed as the net release of nonesterified fatty acids (NEFAs) from femoral and abdominal subcutaneous adipose tissue. Results: Acute hypercortisolemia significantly increased basal and postprandial ATBF in femoral adipose tissue, but the femoral net NEFA release did not change. In abdominal adipose tissue, hypercortisolemia induced substantial increases in basal ATBF and NEFA release. Conclusions: Acute hypercortisolemia induces differential lipolysis and ATBF responses in abdominal and femoral adipose tissue, suggesting depot-specific glucocorticoid effects. Abdominal, but not femoral, adipose tissue contributes to the hypercortisolemia-induced systemic NEFA increase, with likely contributions from other adipose tissue sources and intravascular triglyceride hydrolysis. PMID:28323916

Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS).

PubMed

Borruel, Susana; Fernández-Durán, Elena; Alpañés, Macarena; Martí, David; Alvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2013-03-01

Sexual dimorphism suggests a role for androgens in body fat distribution. Women with polycystic ovary syndrome (PCOS), a mainly androgen excess disorder, often present with abdominal obesity and visceral adiposity. We hypothesized that women with PCOS have a masculinized body fat distribution favoring the deposition of fat in visceral and organ-specific adipose tissue depots. This was a case-control study. The study was conducted at an academic hospital. Women with PCOS (n = 55), women without androgen excess (n = 25), and men (n = 26) presenting with similar body mass index participated in the study. There were no interventions. Ultrasound measurements of adipose tissue depots including sc (minimum and maximum), preperitoneal, ip, mesenteric, epicardial, and perirenal fat thickness were obtained and total body fat mass was estimated using a body fat monitor. Men and patients with PCOS had increased amounts of total body fat compared with control women. Men had increased thickness of intraabdominal adipose tissue depots compared with the control women, with the women with PCOS showing intermediate values that were also higher than those of control women in the case of ip and mesenteric fat thickness and was close to reaching statistical significance in the case of epicardial fat thickness. Women with PCOS also showed increased minimum sc fat thickness compared with the control women. Obesity increased the thickness of all of the adipose tissue depots in the 3 groups of subjects. Women with PCOS have higher global adiposity and increased amounts of visceral adipose tissue compared with control women, especially in the ip and mesenteric depots.

Transient receptor potential canonical channel-1 (TRPC1) KO mice that exercise are protected from high-fat diet-induced obesity and type 2 diabetes risk

USDA-ARS?s Scientific Manuscript database

Objective: Transient receptor potential canonical channel-1 (TRPC1) is a major class of calcium permeable channels found in key metabolic tissues, including the hypothalamus, adipose tissue, and skeletal muscle, making them likely candidates for the regulation of cellular energy metabolism. The exac...

Physical exercise alleviates ER stress in obese humans through reduction in the expression and release of GRP78 chaperone.

PubMed

Khadir, Abdelkrim; Kavalakatt, Sina; Abubaker, Jehad; Cherian, Preethi; Madhu, Dhanya; Al-Khairi, Irina; Abu-Farha, Mohamed; Warsame, Samia; Elkum, Naser; Dehbi, Mohammed; Tiss, Ali

2016-09-01

Perturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise. Subcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient. Levels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1α and eukaryotic initiation factor-2α (eIF2α). Our results suggest that physical exercise alleviates ER stress in human obese through attenuation of GRP78 signaling network. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Exercise Training and Weight Loss on Plasma Fetuin-A Levels and Insulin Sensitivity in Overweight Older Men.

PubMed

Blumenthal, Jacob B; Gitterman, Anna; Ryan, Alice S; Prior, Steven J

2017-01-01

Aerobic exercise training and weight loss (AEX+WL) improves insulin sensitivity in overweight adults; however, the underlying pathways are incompletely understood. Fetuin-A, a hepatokine that inhibits insulin signaling, may be involved in the salutary effects of AEX+WL. Therefore, we examined the effects of 6-month AEX+WL on plasma fetuin-A levels (36-48 hours after the last bout of exercise), aerobic capacity (VO 2max ), body composition, glucose tolerance, and insulin sensitivity (M) in 16 sedentary, overweight-obese older men (age = 60 ± 2 years, BMI = 31 ± 1 kg/m 2 ) with no history of cardiovascular disease or diabetes. At baseline, fetuin-A levels correlated directly with adiposity and had a borderline inverse correlation with M. After AEX+WL, body weight decreased by ~10 kg, while both VO 2max and M increased by 16% ( P < 0.005 for all). Contrary to our hypothesis, plasma fetuin-A levels increased after AEX+WL (1.16 ± 0.10 g/L versus 1.70 ± 0.19 g/L, P = 0.006). This increase was unrelated to changes in body composition or glucose metabolism, but directly correlated with changes in VO 2max ( r = 0.57, P < 0.05). Thus, in overweight-to-obese older men, AEX+WL appears to increase plasma fetuin-A levels. Although not associated with improvements in insulin sensitivity, this increase in fetuin-A was related to improvements in aerobic capacity and could be representative of the cardioprotective effects of AEX+WL in older men.

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

PubMed Central

Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

Disturbance of the reproductive axis induced by negative energy balance.

PubMed

Judd, S J

1998-01-01

Animal reproduction is impaired when intake of energy is so restricted that activities essential to life are threatened; this is seen as a homeostatic adjustment that restricts wasteful energy expenditure. Fasting or exercising to a degree requiring considerable energy expenditure has major effects on the hypothalamus, including activation of corticotrophin-releasing factor (CRF) neurons, suppression of thyrotrophin-releasing hormone synthesis, and increased growth hormone secretion; these are associated with increased concentrations of hypothalamic neuropeptide Y mRNA and are corrected by administration of leptin, an adipose-tissue protein with a tertiary structure similar to the cytokine interleukin-2. This response to fasting results from a disordered pattern of activity in the gonadotrophin-releasing hormone (GnRH) pacemaker, characterized by reduced luteinizing hormone pulsatility, particularly during daytime. Animal studies have suggested that the response depends on an intact afferent vagal system from the stomach and the presence of oestrogen. Noradrenergic neurons forming the A2 group increase the activity of CRF neurons that, in turn, inhibit GnRH pulsatility. Reproductive impairment due to fasting is reversed by leptin, and abnormalities of leptin are described in individuals who fast or who develop exercise-induced amenorrhoea. This paper discusses these changes induced by negative energy balance and speculates on the involvement of leptin as a contributor to these abnormalities.

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

PubMed Central

Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

2013-01-01

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

Liver fat, visceral adiposity, and sleep disturbances contribute to the development of insulin resistance and glucose intolerance in nondiabetic dialysis patients.

PubMed

Sakkas, Giorgos K; Karatzaferi, Christina; Zintzaras, Elias; Giannaki, Christoforos D; Liakopoulos, Vassilios; Lavdas, Eleftherios; Damani, Eleni; Liakos, Nikos; Fezoulidis, Ioannis; Koutedakis, Yiannis; Stefanidis, Ioannis

2008-12-01

Hemodialysis patients exhibit insulin resistance (IR) in target organs such as liver, muscles, and adipose tissue. The aim of this study was to identify contributors to IR and to develop a model for predicting glucose intolerance in nondiabetic hemodialysis patients. After a 2-h, 75-g oral glucose tolerance test (OGTT), 34 hemodialysis patients were divided into groups with normal (NGT) and impaired glucose tolerance (IGT). Indices of insulin sensitivity were derived from OGTT data. Measurements included liver and muscle fat infiltration and central adiposity by computed tomography scans, body composition by dual energy X-ray absorptiometer, sleep quality by full polysomnography, and functional capacity and quality of life (QoL) by a battery of exercise tests and questionnaires. Cut-off points, as well as sensitivity and specificity calculations were based on IR (insulin sensitivity index by Matsuda) using a receiver operator characteristics (ROC) curve analysis. Fifteen patients were assigned to the IGT, and 19 subjects to the NGT group. Intrahepatic fat content and visceral adiposity were significantly higher in the IGT group. IR indices strongly correlated with sleep disturbances, visceral adiposity, functional capacity, and QoL. Visceral adiposity, O2 desaturation during sleep, intrahepatic fat content, and QoL score fitted into the model for predicting glucose intolerance. A ROC curve analysis identified an intrahepatic fat content of > 3.97% (sensitivity, 100; specificity, 35.7) as the best cutoff point for predicting IR. Visceral and intrahepatic fat content, as well as QoL and sleep seemed to be involved at some point in the development of glucose intolerance in hemodialysis patients. Means of reducing fat depots in the liver and splachnic area might prove promising in combating IR and cardiovascular risk in hemodialysis patients.

High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype.

PubMed

Halverstadt, Amy; Phares, Dana A; Ferrell, Robert E; Wilund, Kenneth R; Goldberg, Andrew P; Hagberg, James M

2003-11-01

Plasma high-density lipoprotein cholesterol (HDL-C) levels are an important independent risk factor for cardiovascular disease (CVD) that can be modified through exercise training. However, levels of HDL-C and its subfractions and their response to standardized exercise training are highly variable among individuals. Such variability suggests that levels of HDL-C, its subfractions, and their response to exercise training may be influenced by genetic variation and the interaction of that genetic variation with physical activity. The endothelial lipase gene (LIPG) may influence HDL-C metabolism and has several recently identified genetic variants. We hypothesized that the LIPG Thr111Ile polymorphism would be associated with variation in HDL-C levels and its subfractions and their response to exercise training. Eighty-three sedentary, healthy 50- to 75-year-old subjects were weight-maintained on an American Heart Association Step 1 Diet and then studied before and after aerobic exercise training. Sample size varied according to outcome measure as complete data was not available for all subjects. Initial age, body composition, and maximum oxygen consumption (V02max) did not differ between LIPG genotype groups (CC, n=41 to 44; CT/TT, n=37 to 39). Initial total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels were not significantly different between groups. The CT/TT group had lower initial HDL(2NMR)-C (12 +/- 1.0 v 17 +/- 1.1 mg/dL; P =.002) and integrated HDL(1,2NMR)-C (13 +/- 1.0 v 18 +/- 1.1 mg/dL; P=.002) levels and somewhat higher initial levels of integrated HDL(3,4,5)-C (31 +/- 2.2 v 25 +/- 2.3 mg/dL; P=.06). With exercise training, Vo2max increased, and body weight, total body fat, and visceral adipose tissue decreased similarly in both groups. With training, HDL-C levels increased twice as much (4.4 +/- 0.8 v 1.9 +/- 0.9 mg/dL; P=.04), HDL3-C levels increased almost 2-fold greater (3.8 +/- 0.7 v 2.2 +/- 0.6 mg/dL; P=.07), and HDL(5NMR)-C levels increased more than 4 times as much (2.2 +/- 0.8 v 0.5 +/- 0.6 mg/dL; P=.08) in the CC compared to the CT/TT group. We conclude that the LIPG genotype is associated with interindividual variability in HDL-C and its subfractions and their response to exercise training.

Carnitine Palmitoyltransferase 1B 531K Allele Carriers Sustain a Higher Respiratory Quotient after Aerobic Exercise, but β3-Adrenoceptor 64R Allele Does Not Affect Lipolysis: A Human Model

PubMed Central

Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

2014-01-01

Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome

PubMed Central

O’Reilly, Michael W.; Kempegowda, Punith; Walsh, Mark; Taylor, Angela E.; Manolopoulos, Konstantinos N.; Allwood, J. William; Semple, Robert K.; Hebenstreit, Daniel; Dunn, Warwick B.; Tomlinson, Jeremy W.

2017-01-01

Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS. Methods: We performed a human deep metabolic in vivo phenotyping study examining the systemic and intra-adipose effects of acute and chronic androgen exposure in 10 PCOS women, in comparison with 10 body mass index–matched healthy controls, complemented by in vitro experiments. Results: PCOS women had increased intra-adipose concentrations of testosterone (P = 0.0006) and dihydrotestosterone (P = 0.01), with increased expression of the androgen-activating enzyme aldo-ketoreductase type 1 C3 (AKR1C3) (P = 0.04) in subcutaneous adipose tissue. Adipose glycerol levels in subcutaneous adipose tissue microdialysate supported in vivo suppression of lipolysis after acute androgen exposure in PCOS (P = 0.04). Mirroring this, nontargeted serum metabolomics revealed prolipogenic effects of androgens in PCOS women only. In vitro studies showed that insulin increased adipose AKR1C3 expression and activity, whereas androgen exposure increased adipocyte de novo lipid synthesis. Pharmacologic AKR1C3 inhibition in vitro decreased de novo lipogenesis. Conclusions: These findings define an intra-adipose mechanism of androgen activation that contributes to adipose remodeling and a systemic lipotoxic metabolome, with intra-adipose androgens driving lipid accumulation and insulin resistance in PCOS. AKR1C3 represents a promising therapeutic target in PCOS. PMID:28645211

AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome.

PubMed

O'Reilly, Michael W; Kempegowda, Punith; Walsh, Mark; Taylor, Angela E; Manolopoulos, Konstantinos N; Allwood, J William; Semple, Robert K; Hebenstreit, Daniel; Dunn, Warwick B; Tomlinson, Jeremy W; Arlt, Wiebke

2017-09-01

Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS. We performed a human deep metabolic in vivo phenotyping study examining the systemic and intra-adipose effects of acute and chronic androgen exposure in 10 PCOS women, in comparison with 10 body mass index-matched healthy controls, complemented by in vitro experiments. PCOS women had increased intra-adipose concentrations of testosterone (P = 0.0006) and dihydrotestosterone (P = 0.01), with increased expression of the androgen-activating enzyme aldo-ketoreductase type 1 C3 (AKR1C3) (P = 0.04) in subcutaneous adipose tissue. Adipose glycerol levels in subcutaneous adipose tissue microdialysate supported in vivo suppression of lipolysis after acute androgen exposure in PCOS (P = 0.04). Mirroring this, nontargeted serum metabolomics revealed prolipogenic effects of androgens in PCOS women only. In vitro studies showed that insulin increased adipose AKR1C3 expression and activity, whereas androgen exposure increased adipocyte de novo lipid synthesis. Pharmacologic AKR1C3 inhibition in vitro decreased de novo lipogenesis. These findings define an intra-adipose mechanism of androgen activation that contributes to adipose remodeling and a systemic lipotoxic metabolome, with intra-adipose androgens driving lipid accumulation and insulin resistance in PCOS. AKR1C3 represents a promising therapeutic target in PCOS. Copyright © 2017 Endocrine Society

Anthropometric Measures After Fontan Procedure: Implications for Suboptimal Functional Outcome

PubMed Central

Cohen, Meryl S.; Zak, Victor; Atz, Andrew M.; Printz, Beth F.; Pinto, Nelangi; Lambert, Linda; Pemberton, Victoria; Li, Jennifer S.; Margossian, Renee; Dunbar-Masterson, Carolyn; McCrindle, Brian W.

2010-01-01

Background Abnormal height and adiposity are observed after the Fontan operation. These abnormalities may be associated with worse functional outcome. Methods We analyzed data from the NHLBI Pediatric Heart Network cross-sectional study of Fontan patients. Groups were defined by height (z-score < −1.5 or ≥ −1.5) and body mass index (BMI z-score ≤ −1.5 or −1.5 to 1.5 or ≥ 1.5). Associations of anthropometric measures with measurements from clinical testing (exercise, echocardiography, MRI) were determined adjusting for demographics, anatomy, and pre-Fontan status. Relationships between anthropometric measures and functional health status (FHS) were assessed using the Child Health Questionnaire. Results Mean age of the cohort (n=544) was 11.9±3.4 years. Lower height-z patients (n=124, 23%) were more likely to have pre-Fontan atrioventricular valve regurgitation (p=0.029), as well as orthopedic and developmental problems (both p<0.001). Lower height-z patients also had lower physical and psychosocial FHS summary scores (both p <0.01). Higher BMI-z patients (n=45, 8%) and lower BMI-z patients (n=53, 10%) did not have worse FHS compared to midrange BMI-z patients (n=446, 82%). However, higher BMI-z patients had higher ventricular mass-to-volume ratio (p =0.03) and lower % predicted maximum work (p=0.004) compared to midrange and lower BMI-z patients. Conclusions Abnormal anthropometry is common in Fontan patients. Shorter stature is associated with poorer FHS and non-cardiac problems. Increased adiposity is associated with more ventricular hypertrophy and poorer exercise performance, which may have significant long-term implications in this at-risk population. PMID:21146663

Sugar intake is correlated with adiposity and obesity indicators and sedentary lifestyle in Brazilian individuals with morbid obesity.

PubMed

Penatti, M I B; Lira, F S; Katashima, C K; Rosa, J C; Pimentel, G D

2012-01-01

Obesity is a chronic disease characterized by increased accumulation of body fat. We evaluated the socioeconomic aspects, body composition, risk of metabolic complications associated with obesity, eating habits and lifestyle in both women and men adults and elderly with body mass index (BMI) > 40 kg/m². Among the subjects studied, 79% (n = 32) are female, 5% (n = 2) smokers, 39% (n = 16) use alcohol and only 24% (n = 10) are practitioners of physical exercise. The higher food intake was breads, followed by rice. The daily intake of fruits and vegetables is low. Positive correlation between consumption of sugar and BMI and abdominal circumference (AC) was observed. In summary, was found that morbidly obese patients that looking for nutritional counseling presents increased body fat, poor eating habits and sedentary lifestyle.

The contribution of childhood cardiorespiratory fitness and adiposity to inflammation in young adults.

PubMed

Sun, Cong; Magnussen, Costan G; Ponsonby, Anne-Louise; Schmidt, Michael D; Carlin, John B; Huynh, Quan; Venn, Alison J; Dwyer, Terence

2014-12-01

Cardiorespiratory fitness and adiposity may influence cardiovascular risk through their effects on inflammation. The long-term effects of these modifiable factors on adult inflammation remain uncertain. The associations of childhood and adulthood cardiorespiratory fitness and adiposity with adult inflammation [C-reactive protein (CRP), fibrinogen] were examined. 1,976 children examined in 1985 and re-examined as young adults in 2004-2006 were included. Cardiorespiratory fitness and adiposity were assessed at both waves. CRP and fibrinogen were measured at follow-up. Higher childhood fitness was associated with lower adult inflammation in both sexes. After adjusting for childhood adiposity, the association with CRP attenuated in males, but remained in females (average reduction of CRP 18.1% (95% CI 11.3-24.4%) per 1-SD increase in childhood fitness). Higher adult fitness, adjusting for childhood fitness (an increase in fitness from childhood to adulthood), was associated with lower adult CRP in females and lower fibrinogen in males. Higher childhood and adulthood adiposity (an increase in adiposity from childhood to adulthood) were associated with higher adult inflammation in both sexes. Prevention programs to increase fitness and reduce adiposity in childhood, and maintain a favorable fitness and weight into adulthood, may lead to reduction in adult systemic inflammation. © 2014 The Obesity Society.

The Metabolic Cost of a High Intensity Exercise Program During Bed Rest

NASA Technical Reports Server (NTRS)

Hackney, Kyle; Everett, Meghan; Guined, Jamie; Cunningham, Daid

2012-01-01

Background: Given that disuse-related skeletal muscle atrophy may be exacerbated by an imbalance between energy intake and output, the amount of energy required to complete exercise countermeasures is an important consideration in the well being of subject health during bed rest and spaceflight. Objective: To evaluate the energy cost of a high intensity exercise program performed during short duration bed rest. Methods: 9 subjects (8 male and 1 female; 34.5 +/- 8.2 years) underwent 14 days of bed rest and exercise countermeasures. Exercise energy expenditure and excess post exercise oxygen consumption (EPOC) were collected once in each of 5 different exercise protocols (30 second, 2 minute and 4 minute intervals, continuous aerobic and a variety of resistance exercises) during bed rest. Body mass, basal metabolic rate (BMR), upper and lower leg muscle, subcutaneous, and intramuscular adipose tissue (IMAT) volumes were assessed before and at the end of bed rest. Results: There were no significant differences in body mass (pre: 75.1 +/- 10.5 kg; post: 75.2 +/- 10.1 kg), BMR (pre: 1649 +/- 216 kcal; post: 1657 +/- 177 kcal), muscle subcutaneous, or IMAT volumes (Table 2) after 14 days of bed rest and exercise. Body mass was maintained with an average daily intake of 2710 +/- 262 kcal (36.2 +/- 2.1 kcal/kg/day), while average daily energy expenditure was 2579 +/-311 kcal (34.5 +/- 3.6 kcal/kg/day). Exercise energy expenditure was significantly greater as a result of continuous aerobic exercise than all other exercise protocols.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

PubMed

LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

PubMed Central

Otani, Hajime

2013-01-01

Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span. PMID:23738041

Advances in Exercise, Fitness, and Performance Genomics in 2015.

PubMed

Sarzynski, Mark A; Loos, Ruth J F; Lucia, Alejandro; Pérusse, Louis; Roth, Stephen M; Wolfarth, Bernd; Rankinen, Tuomo; Bouchard, Claude

2016-10-01

This review of the exercise genomics literature encompasses the highest-quality articles published in 2015 across seven broad topics: physical activity behavior, muscular strength and power, cardiorespiratory fitness and endurance performance, body weight and adiposity, insulin and glucose metabolism, lipid and lipoprotein metabolism, and hemodynamic traits. One study used a quantitative trait locus for wheel running in mice to identify single nucleotide polymorphisms (SNPs) in humans associated with physical activity levels. Two studies examined the association of candidate gene ACTN3 R577X genotype on muscular performance. Several studies examined gene-physical activity interactions on cardiometabolic traits. One study showed that physical inactivity exacerbated the body mass index (BMI)-increasing effect of an FTO SNP but only in individuals of European ancestry, whereas another showed that high-density lipoprotein cholesterol (HDL-C) SNPs from genome-wide association studies exerted a smaller effect in active individuals. Increased levels of moderate-to-vigorous-intensity physical activity were associated with higher Matsuda insulin sensitivity index in PPARG Ala12 carriers but not Pro12 homozygotes. One study combined genome-wide and transcriptome-wide profiling to identify genes and SNPs associated with the response of triglycerides (TG) to exercise training. The genome-wide association study results showed that four SNPs accounted for all of the heritability of △TG, whereas the baseline expression of 11 genes predicted 27% of △TG. A composite SNP score based on the top eight SNPs derived from the genomic and transcriptomic analyses was the strongest predictor of ΔTG, explaining 14% of the variance. The review concludes with a discussion of a conceptual framework defining some of the critical conditions for exercise genomics studies and highlights the importance of the recently launched National Institutes of Health Common Fund program titled "Molecular Transducers of Physical Activity in Humans."

Brown adipose tissue

PubMed Central

Townsend, Kristy; Tseng, Yu-Hua

2012-01-01

Obesity is currently a global pandemic, and is associated with increased mortality and co-morbidities including many metabolic diseases. Obesity is characterized by an increase in adipose mass due to increased energy intake, decreased energy expenditure, or both. While white adipose tissue is specialized for energy storage, brown adipose tissue has a high concentration of mitochondria and uniquely expresses uncoupling protein 1, enabling it to be specialized for energy expenditure and thermogenesis. Although brown fat was once considered only necessary in babies, recent morphological and imaging studies have provided evidence that, contrary to prior belief, this tissue is present and active in adult humans. In recent years, the topic of brown adipose tissue has been reinvigorated with many new studies regarding brown adipose tissue differentiation, function and therapeutic promise. This review summarizes the recent advances, discusses the emerging questions and offers perspective on the potential therapeutic applications targeting this tissue. PMID:23700507

Body mass index bias in defining obesity of diverse young adults: The Training Intervention and Genetics of Exercise Response (TIGER) Study

USDA-ARS?s Scientific Manuscript database

The BMI cut-score used to define overweight and obesity was derived primarily using data from Caucasian men and women. The present study evaluated the racial/ethnic bias of BMI to estimate the adiposity of young men and women (aged 17–35 years) using dual-energy X-ray absorptiometry (DXA) determinat...

Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism

PubMed Central

Cochran, Blake J.; Hou, Liming; Manavalan, Anil Paul Chirackal; Moore, Benjamin M.; Tabet, Fatiha; Sultana, Afroza; Cuesta Torres, Luisa; Tang, Shudi; Shrestha, Sudichhya; Senanayake, Praween; Patel, Mili; Ryder, William J.; Bongers, Andre; Maraninchi, Marie; Wasinger, Valerie C.; Westerterp, Marit; Tall, Alan R.; Barter, Philip J.

2016-01-01

Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes. PMID:27702832

Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

PubMed Central

Camacho, Jaime; Duque, Juan; Carreño, Marisol; Acero, Edward; Pérez, Máximo; Ramirez, Sergio; Umaña, Juan; Obando, Carlos; Guerrero, Albert; Sandoval, Néstor; Rodríguez, Gina

2017-01-01

Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases. PMID:29209367

Caveolin-1 Deficiency Leads to Increased Susceptibility to Cell Death and Fibrosis in White Adipose Tissue: Characterization of a Lipodystrophic Model

PubMed Central

Stanley, Amanda C.; Bastiani, Michele; Okano, Satomi; Nixon, Susan J.; Thomas, Gethin; Stow, Jennifer L.; Parton, Robert G.

2012-01-01

Caveolin-1 (CAV1) is an important regulator of adipose tissue homeostasis. In the present study we examined the impact of CAV1 deficiency on the properties of mouse adipose tissue both in vivo and in explant cultures during conditions of metabolic stress. In CAV1−/− mice fasting caused loss of adipose tissue mass despite a lack of hormone-sensitive lipase (HSL) phosphorylation. In addition, fasting resulted in increased macrophage infiltration, enhanced deposition of collagen, and a reduction in the level of the lipid droplet protein perilipin A (PLIN1a). Explant cultures of CAV1−/− adipose tissue also showed a loss of PLIN1a during culture, enhanced secretion of IL-6, increased release of lactate dehydrogenase, and demonstrated increased susceptibility to cell death upon collagenase treatment. Attenuated PKA-mediated signaling to HSL, loss of PLIN1a and increased secretion of IL-6 were also observed in adipose tissue explants of CAV1+/+ mice with diet-induced obesity. Together these results suggest that while alterations in adipocyte lipid droplet biology support adipose tissue metabolism in the absence of PKA-mediated pro-lipolytic signaling in CAV1−/− mice, the tissue is intrinsically unstable resulting in increased susceptibility to cell death, which we suggest underlies the development of fibrosis and inflammation during periods of metabolic stress. PMID:23049990

The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis

PubMed Central

Davis, Kathryn E.; D. Neinast, Michael; Sun, Kai; M. Skiles, William; D. Bills, Jessica; A. Zehr, Jordan; Zeve, Daniel; D. Hahner, Lisa; W. Cox, Derek; M. Gent, Lana; Xu, Yong; V. Wang, Zhao; A. Khan, Sohaib; Clegg, Deborah J.

2013-01-01

Our data demonstrate that estrogens, estrogen receptor-α (ERα), and estrogen receptor-β (ERβ) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that αERKO mice have increased adipose tissue inflammation and fibrosis prior to obesity onset. Selective deletion of adipose tissue ERα in adult mice using a novel viral vector technology recapitulated the findings in the total body ERα null mice. Generation of a novel mouse model, lacking ERα specifically from adipocytes (AdipoERα), demonstrated increased markers of fibrosis and inflammation, especially in the males. Additionally, we found that the beneficial effects of estrogens on adipose tissue require adipocyte ERα. Lastly, we determined the role of ERβ in regulating inflammation and fibrosis, by breeding the AdipoERα into the βERKO background and found that in the absence of adipocyte ERα, ERβ has a protective role. These data suggest that adipose tissue and adipocyte ERα protects against adiposity, inflammation, and fibrosis in both males and females. PMID:24049737

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements.

PubMed

Lakeland, Thomas V; Borg, Melissa L; Matzaris, Maria; Abdelkader, Amany; Evans, Roger G; Watt, Matthew J

2014-06-15

Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo. Copyright © 2014 the American Physiological Society.

Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study.

PubMed

Miller, Melissa R; Pereira, Rocio I; Langefeld, Carl D; Lorenzo, Carlos; Rotter, Jerome I; Chen, Yii-Der Ida; Bergman, Richard N; Wagenknecht, Lynne E; Norris, Jill M; Fingerlin, Tasha E

2012-09-01

We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S(I)); and 3) levels of adiposity and S(I), additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S(I.) After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10(-3); SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S(I) (P = 8.10 × 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S(I) (BMI: P = 4.98 × 10(-71); VAT: P = 1.48 × 10(-64); SAT: P = 4.21 × 10(-62)), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S(I) (P = 0.021). Although levels of circulating FFA are associated both with increasing adiposity and decreasing S(I), they do not appear to mediate the association between levels of adiposity and S(I) in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.

Obesity, Inflammation, and Cancer.

PubMed

Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A

2016-05-23

Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.

Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/db mice.

PubMed

Mihara, Masatomo; Aihara, Ken-ichi; Ikeda, Yasumasa; Yoshida, Sumiko; Kinouchi, Mizuho; Kurahashi, Kiyoe; Fujinaka, Yuichi; Akaike, Masashi; Matsumoto, Toshio

2010-02-01

The binding of thrombin to its receptor stimulates inflammatory cytokines including IL-6 and monocyte chemoattractant protein-1 (MCP-1); both are associated with the development of insulin resistance. Because increased adiposity enhanced the expression of coagulation factor VII that stimulates the coagulation pathway in adipose tissue, we tested whether the inhibition of thrombin action ameliorates insulin resistance in obese diabetic (Lpr(-/-):db/db) mice. The 4-wk administration of argatroban, a selective thrombin inhibitor, reduced fasting plasma glucose and ameliorated insulin resistance in these mice. It also reduced adipocyte size and macrophage infiltration into adipose tissue. The aberrant gene expression of MCP-1, IL-6, adiponectin, and factor VII and suppressed insulin receptor substrate-1-Akt signaling in adipose tissue of db/db mice were reversed by argatroban treatment. These results demonstrate that increased adiposity enhances the production of thrombin in adipose tissue by stimulating factor VII expression and suggest that increased thrombin activity in adipose tissue plays an important role in the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation.

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

PubMed

Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

2011-05-01

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

Neutron organ dose and the influence of adipose tissue

NASA Astrophysics Data System (ADS)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

The aging musculoskeletal system and obesity-related considerations with exercise

PubMed Central

Vincent, Heather K.; Raiser, Sara N.; Vincent, Kevin R.

2012-01-01

Advancing age and adiposity contribute to musculoskeletal degenerative diseases and the development of sarcopenic obesity. The etiology of muscle loss is multifactorial, and includes inflammation, oxidative stress and hormonal changes, and is worsened by activity avoidance due to fear of pain. The risk for mobility disability and functional impairment rises with severity of obesity in the older adult. Performance measures of walking distance, walking speed, chair rise, stair climb, body transfers and ability to navigate obstacles on a course are adversely affected in this population, and this reflects decline in daily physical functioning. Exercise training is an ideal intervention to counteract the effects of aging and obesity. The 18 randomized controlled trials of exercise studies with or without diet components reviewed here indicate that 3–18 month programs that included aerobic and strengthening exercise (2–3 days per week) with caloric restriction (typically 750 kcal deficit/day), induced the greatest change in functional performance measures compared with exercise or diet alone. Importantly, resistance exercise attenuates muscle mass loss with the interventions. These interventions can also combat factors that invoke sarcopenia, including inflammation, oxidative stress and insulin resistance. Therefore, regular multimodal exercise coupled with diet appears to be very effective for counteracting sarocpenic obesity and improving mobility and function in the older, obese adult. PMID:22440321

Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

PubMed Central

Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K. N.; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S. Sendhil

2016-01-01

Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID:27197769

Exercise Prescription in Patients with Different Combinations of Cardiovascular Disease Risk Factors: A Consensus Statement from the EXPERT Working Group.

PubMed

Hansen, Dominique; Niebauer, Josef; Cornelissen, Veronique; Barna, Olga; Neunhäuserer, Daniel; Stettler, Christoph; Tonoli, Cajsa; Greco, Eugenio; Fagard, Robert; Coninx, Karin; Vanhees, Luc; Piepoli, Massimo F; Pedretti, Roberto; Ruiz, Gustavo Rovelo; Corrà, Ugo; Schmid, Jean-Paul; Davos, Constantinos H; Edelmann, Frank; Abreu, Ana; Rauch, Bernhard; Ambrosetti, Marco; Braga, Simona Sarzi; Beckers, Paul; Bussotti, Maurizio; Faggiano, Pompilio; Garcia-Porrero, Esteban; Kouidi, Evangelia; Lamotte, Michel; Reibis, Rona; Spruit, Martijn A; Takken, Tim; Vigorito, Carlo; Völler, Heinz; Doherty, Patrick; Dendale, Paul

2018-05-04

Whereas exercise training is key in the management of patients with cardiovascular disease (CVD) risk (obesity, diabetes, dyslipidaemia, hypertension), clinicians experience difficulties in how to optimally prescribe exercise in patients with different CVD risk factors. Therefore, a consensus statement for state-of-the-art exercise prescription in patients with combinations of CVD risk factors as integrated into a digital training and decision support system (the EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool) needed to be established. EXPERT working group members systematically reviewed the literature for meta-analyses, systematic reviews and/or clinical studies addressing exercise prescriptions in specific CVD risk factors and formulated exercise recommendations (exercise training intensity, frequency, volume and type, session and programme duration) and exercise safety precautions, for obesity, arterial hypertension, type 1 and 2 diabetes, and dyslipidaemia. The impact of physical fitness, CVD risk altering medications and adverse events during exercise testing was further taken into account to fine-tune this exercise prescription. An algorithm, supported by the interactive EXPERT tool, was developed by Hasselt University based on these data. Specific exercise recommendations were formulated with the aim to decrease adipose tissue mass, improve glycaemic control and blood lipid profile, and lower blood pressure. The impact of medications to improve CVD risk, adverse events during exercise testing and physical fitness was also taken into account. Simulations were made of how the EXPERT tool provides exercise prescriptions according to the variables provided. In this paper, state-of-the-art exercise prescription to patients with combinations of CVD risk factors is formulated, and it is shown how the EXPERT tool may assist clinicians. This contributes to an appropriately tailored exercise regimen for every CVD risk patient.

Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers.

PubMed

Mazur-Bialy, Agnieszka Irena; Bilski, Jan; Wojcik, Dagmara; Brzozowski, Bartosz; Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Chmura, Anna; Magierowski, Marcin; Magierowska, Katarzyna; Mach, Tomasz; Brzozowski, Tomasz

2017-04-20

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn's disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 ( p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice ( p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice ( p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin.

Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers

PubMed Central

Mazur-Bialy, Agnieszka Irena; Bilski, Jan; Wojcik, Dagmara; Brzozowski, Bartosz; Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Chmura, Anna; Magierowski, Marcin; Magierowska, Katarzyna; Mach, Tomasz; Brzozowski, Tomasz

2017-01-01

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn‘s disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice (p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin. PMID:28425943

Effect of whole-body vibration training on body composition, exercise performance and biochemical responses in middle-aged mice.

PubMed

Lin, Ching-I; Huang, Wen-Ching; Chen, Wen-Chyuan; Kan, Nai-Wen; Wei, Li; Chiu, Yen-Shuo; Huang, Chi-Chang

2015-09-01

Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential benefits of WBV on aging-associated changes in body composition, exercise performance, and fatigue are currently unclear. The objective of the study is to investigate the beneficial effects of WBV training on body composition, exercise performance, and physical fatigue-related and biochemical responses in middle-aged mice. In total, 24 male C57BL/6 mice aged 15 months old were randomly divided into 3 groups (n=8 per group): sedentary control (SC), relatively low-frequency WBV (5.6 Hz, 2 mm, 0.13 g) (LV), and relatively high-frequency WBV (13 Hz, 2 mm, 0.68 g) (HV). Mice in the LV and HV groups were placed inside a vibration platform and vibrated at different frequencies and fixed amplitude (2 mm) for 15 min, 5 days/week for 4 weeks. Exercise performance, core temperature and anti-fatigue function were evaluated by forelimb grip strength and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after a 15-min swimming exercise, as were changes in body composition and biochemical variables at the end of the experiment. Relative muscle and brown adipose tissue weight (%) was significantly higher for the HV than SC mice, but relative liver weight (%) was lower. On trend analysis, WBV increased grip strength, aerobic endurance and core temperature in mice. As well, serum lactate, ammonia and CK levels were dose-dependently decreased with vibration frequency after the swimming test. Fasting serum levels of albumin and total protein were increased and serum levels of alkaline phosphatase and creatinine decreased dose-dependently with vibration frequency. Moreover, WBV training improved the age-related abnormal morphology of skeletal muscle, liver and kidney tissues. Therefore, it could improve exercise performance and ameliorate fatigue and prevent senescence-associated biochemical and pathological alterations in middle-aged mice. WBV training may be an effective intervention for health promotion in the aging population. The detailed molecular mechanism of how WBV training regulates anti-aging activity warrants further functional studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Decreased RB1 mRNA, Protein, and Activity Reflect Obesity-Induced Altered Adipogenic Capacity in Human Adipose Tissue

PubMed Central

Moreno-Navarrete, José María; Petrov, Petar; Serrano, Marta; Ortega, Francisco; García-Ruiz, Estefanía; Oliver, Paula; Ribot, Joan; Ricart, Wifredo; Palou, Andreu; Bonet, Mª Luisa; Fernández-Real, José Manuel

2013-01-01

Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice. No studies have been reported thus far in human adipose tissue or human adipocytes. We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models. Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPARγ and IRS1) in both visceral and subcutaneous human adipose tissue. BMI increase was the main contributor to adipose RB1 downregulation. In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss. RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation. In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype. In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes. Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes. PMID:23315497

Abdominal adiposity and hot flashes among midlife women.

PubMed

Thurston, Rebecca C; Sowers, MaryFran R; Sutton-Tyrrell, Kim; Everson-Rose, Susan A; Lewis, Tené T; Edmundowicz, Daniel; Matthews, Karen A

2008-01-01

Two competing hypotheses suggest how adiposity may affect menopausal hot flashes. The "thin hypothesis" asserts that aromatization of androgens to estrogens in body fat should be associated with decreased hot flashes. Conversely, thermoregulatory models argue that body fat should be associated with increased hot flashes. The study objective was to examine associations between abdominal adiposity and hot flashes, including the role of reproductive hormones in these associations. The Study of Women's Health Across the Nation Heart Study (2001-2003) is an ancillary study to the Study of Women's Health Across the Nation, a community-based cohort study. Participants were 461 women (35% African American, 65% white) ages 45 to 58 years with an intact uterus and at least one ovary. Measures included a computed tomography scan to assess abdominal adiposity; reported hot flashes over the previous 2 weeks; and a blood sample for measurement of follicle-stimulating hormone, estradiol, and sex hormone-binding globulin-adjusted estradiol (free estradiol index). Associations were evaluated within multivariable logistic and linear regression models. Every 1-SD increase in total (odds ratio [OR]=1.28; 95% CI: 1.06-1.55) and subcutaneous (OR=1.30; 95% CI: 1.07-1.58) abdominal adiposity was associated with increased odds of hot flashes in age- and site-adjusted models. Visceral adiposity was not associated with hot flashes. Associations were not reduced when models included reproductive hormone concentrations. Increased abdominal adiposity, particularly subcutaneous adiposity, is associated with increased odds of hot flashes, favoring thermoregulatory models of hot flashes. Body fat may not protect women from hot flashes as once thought.

Association of Changes in Abdominal Fat and Cardiovascular Risk Factors

PubMed Central

Lee, Jane J.; Pedley, Alison; Hoffmann, Udo; Massaro, Joseph M.; Fox, Caroline S.

2017-01-01

BACKGROUND Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are associated with adverse cardiometabolic risk profiles. OBJECTIVES This study explored the degree to which changes in abdominal fat quantity and quality are associated with changes in cardiovascular disease (CVD) risk factors. METHODS Study participants (n = 1,106; 44.1% women; mean baseline age 45.1 years) were drawn from the Framingham Heart Study Third Generation cohort who participated in the computed tomography (CT) substudy Exams 1 and 2. Participants were followed for 6.1 years on average. Abdominal adipose tissue volume in cm3 and attenuation in Hounsfield units (HU) were determined by CT-acquired abdominal scans. RESULTS The mean fat volume change was an increase of 602 cm3 for SAT and an increase of 703 cm3 for VAT; the mean fat attenuation change was a decrease of 5.5HU for SAT and an increase of 0.07 HU for VAT. An increase in fat volume and decrease in fat attenuation were associated with adverse changes in CVD risk factors. An additional 500 cm3 increase in fat volume was associated with incident hypertension (odds ratio [OR]: 1.21 for SAT; OR: 1.30 for VAT), hypertriglyceridemia (OR: 1.15 for SAT; OR: 1.56 for VAT), and metabolic syndrome (OR: 1.43 for SAT; OR: 1.82 for VAT; all p < 0.05). Similar trends were observed for each additional 5 HU decrease in abdominal adipose tissue attenuation. Most associations remained significant even after further accounting for body mass index change, waist circumference change, or respective abdominal adipose tissue volumes. CONCLUSIONS Increasing accumulation of fat quantity and decreasing fat attenuation are associated with worsening of CVD risk factors beyond the associations with generalized adiposity, central adiposity, or respective adipose tissue volumes. PMID:27687192

Neighbourhood poverty, perceived discrimination, and central adiposity: Independent associations in a repeated measures analysis

PubMed Central

Kwarteng, Jamila L.; Schulz, Amy J.; Mentz, Graciela B.; Israel, Barbara A.; Shanks, Trina R.; White Perkins, Denise

2018-01-01

SUMMARY This study examines the independent effects of neighbourhood context (i.e. neighbourhood poverty) and exposure to perceived discrimination in shaping risk of obesity over time. Weighted 3-level hierarchical linear regression models for a continuous outcome were used to assess independent effects of neighbourhood poverty and perceived discrimination on obesity over time in a sample of 157 Non-Hispanic Black, Non-Hispanic White, and Hispanic adults 2002/2003 and 2007/2008. Independent associations were found between neighbourhood poverty and perceived discrimination with central adiposity over time. Residents of neighbourhoods with high concentrations of poverty were more likely to show increases in central adiposity compared to those in neighbourhoods with lower concentrations of poverty. In models adjusted for BMI, neighbourhood poverty at baseline was associated with greater change in central adiposity among participants who lived in neighbourhoods in the second (B=3.79, P=0.025) and third (B=3.73, P=0.024) quartiles, compared with those in the lowest poverty neighbourhoods. Results from models that included both neighbourhood poverty and perceived discrimination showed that both neighbourhood poverty and discrimination were associated with increased risk of increased central adiposity over time. Residents of neighbourhoods in the second (B=9.58, P<0.001), third (B=8.25, P=0.004), and fourth (B=7.66, P=0.030) quartiles of poverty remained more likely to show greater increases in central adiposity over time, compared with those in the lowest poverty quartile, mean discrimination at baseline independently and positively associated with increases in central adiposity over time (B= 2.36, P=0.020). These results suggest that neighbourhood poverty and perceived discrimination are independently associated with heightened risk of increases in central adiposity over time. Efforts to address persistent disparities in the central adiposity in the USA should include strategies to reduce high concentrations of neighbourhood poverty as well as discrimination. PMID:27238086

NEIGHBOURHOOD POVERTY, PERCEIVED DISCRIMINATION AND CENTRAL ADIPOSITY IN THE USA: INDEPENDENT ASSOCIATIONS IN A REPEATED MEASURES ANALYSIS.

PubMed

Kwarteng, Jamila L; Schulz, Amy J; Mentz, Graciela B; Israel, Barbara A; Shanks, Trina R; Perkins, Denise White

2016-11-01

This study examines the independent effects of neighbourhood context (i.e. neighbourhood poverty) and exposure to perceived discrimination in shaping risk of obesity over time. Weighted three-level hierarchical linear regression models for a continuous outcome were used to assess the independent effects of neighbourhood poverty and perceived discrimination on obesity over time in a sample of 157 non-Hispanic Black, non-Hispanic White and Hispanic adults in Detroit, USA, in 2002/2003 and 2007/2008. Independent associations were found between neighbourhood poverty and perceived discrimination with central adiposity over time. Residents of neighbourhoods with high concentrations of poverty were more likely to show increases in central adiposity compared with those in neighbourhoods with lower concentrations of poverty. In models adjusted for BMI, neighbourhood poverty at baseline was associated with a greater change in central adiposity among participants who lived in neighbourhoods in the second (B=3.79, p=0.025) and third (B=3.73, p=0.024) poverty quartiles, compared with those in the lowest poverty neighbourhoods. The results from models that included both neighbourhood poverty and perceived discrimination showed that both were associated with increased risk of increased central adiposity over time. Residents of neighbourhoods in the second (B=9.58, p<0.001), third (B=8.25, p=0.004) and fourth (B=7.66, p=0.030) quartiles of poverty were more likely to show greater increases in central adiposity over time, compared with those in the lowest poverty quartile, with mean discrimination at baseline independently and positively associated with increases in central adiposity over time (B=2.36, p=0.020). The results suggest that neighbourhood poverty and perceived discrimination are independently associated with a heightened risk of increase in central adiposity over time. Efforts to address persistent disparities in central adiposity in the USA should include strategies to reduce high concentrations of neighbourhood poverty as well as discrimination.

Exercise effects on fitness, lipids, glucose tolerance and insulin levels in young adults.

PubMed

Israel, R G; Davidson, P C; Albrink, M J; Krall, J M

1981-07-01

The effect of 3 different physical training programs on cardiorespiratory (cr) fitness, fasting plasma lipids, glucose and insulin levels, and scapular skinfold thickness was assessed in 64 healthy college men. Training sessions were held 4 times a week for 5 weeks. The cr fitness improved significantly and skinfold thickness decreased following the aerobic, the pulse workout (interval training), and the anaerobic training compared to the control group. Skinfold thickness, plasma insulin, and triglyceride concentrations were significantly intercorrelated before and after training. The exercise programs had no significant effect on plasma cholesterol, triglycerides, phospholipids, glucose tolerance, or insulin levels. Change in adipose mass was thus dissociated from change in plasma insulin and triglyceride concentrations. It was concluded that in young men plasma triglycerides, the lipid component mostly readily reduced by exercise, were too low to be reduced further by a physical training program.

Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial.

PubMed

Gepner, Yftach; Shelef, Ilan; Schwarzfuchs, Dan; Zelicha, Hila; Tene, Lilac; Yaskolka Meir, Anat; Tsaban, Gal; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Komy, Oded; Wolak, Arik; Chassidim, Yoash; Golan, Rachel; Avni-Hassid, Hila; Bilitzky, Avital; Sarusi, Benjamin; Goshen, Eyal; Shemesh, Elad; Henkin, Yaakov; Stumvoll, Michael; Blüher, Matthias; Thiery, Joachim; Ceglarek, Uta; Rudich, Assaf; Stampfer, Meir J; Shai, Iris

2018-03-13

We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m 2 ), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P <0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P <0.001). The PA + groups significantly increased the metabolic equivalents per week versus the PA - groups (19.0 versus 2.1; P =0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LC PA+ group ( P <0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA + with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm 2 ; 95% confidence interval, -14.8 to -0.45) compared with PA - . The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats ( P <0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724. © 2017 American Heart Association, Inc.

Differences in regional adiposity, bone mineral density, and physical exercise participation based on exercise self-efficacy among senior adults.

PubMed

Glenn, J M; Gray, M; Vincenzo, J L

2015-10-01

The impact of exercise self-efficacy levels (ESE) on exercise participation, levels of body fat (BF), and bone mineral density (BMD) are unclear in senior-aged adults. The purpose of this study was to investigate effects of ESE on exercise participation, regional distribution of BF, and BMD among seniors. Senior adults (N.=76; 36 males, 40 females) were separated into tertiles (T1, age=60.4±1.4; T2, age=61.3±1.4; T3, age=60.4±1.5) based on self-reported levels of ESE. BMD and regional BF were measured using dual-energy x-ray absorptiometry and exercise participation levels were measured using the Rapid Physical-Activity Questionnaire. MANOVA revealed a significant Wilks Lambda (p < 0.001) and univariate analysis was completed for exercise participation levels, android BF, gynoid BF, and spinal BMD. ANOVA revealed T3 was significantly lower for android BF (p=0.002) than T1 and T2 (30% and 26%, respectively) while gynoid BF was significantly lower (p=0.012) for T3 (24%) compared to T1. When evaluating exercise participation levels, T3 was significantly higher (p < 0.001) than T1 or T2. Spinal BMD was significantly higher (p=0.030) between T2 (10%) and T1. ESE is an important factor in senior adults ability to maintain longitudinal health.

Understanding the factors that effect maximal fat oxidation.

PubMed

Purdom, Troy; Kravitz, Len; Dokladny, Karol; Mermier, Christine

2018-01-01

Lipids as a fuel source for energy supply during submaximal exercise originate from subcutaneous adipose tissue derived fatty acids (FA), intramuscular triacylglycerides (IMTG), cholesterol and dietary fat. These sources of fat contribute to fatty acid oxidation (FAox) in various ways. The regulation and utilization of FAs in a maximal capacity occur primarily at exercise intensities between 45 and 65% VO 2max , is known as maximal fat oxidation (MFO), and is measured in g/min. Fatty acid oxidation occurs during submaximal exercise intensities, but is also complimentary to carbohydrate oxidation (CHOox). Due to limitations within FA transport across the cell and mitochondrial membranes, FAox is limited at higher exercise intensities. The point at which FAox reaches maximum and begins to decline is referred to as the crossover point. Exercise intensities that exceed the crossover point (~65% VO 2max ) utilize CHO as the predominant fuel source for energy supply. Training status, exercise intensity, exercise duration, sex differences, and nutrition have all been shown to affect cellular expression responsible for FAox rate. Each stimulus affects the process of FAox differently, resulting in specific adaptions that influence endurance exercise performance. Endurance training, specifically long duration (>2 h) facilitate adaptations that alter both the origin of FAs and FAox rate. Additionally, the influence of sex and nutrition on FAox are discussed. Finally, the role of FAox in the improvement of performance during endurance training is discussed.

Evidence for the effects of yogurt on gut health and obesity.

PubMed

Pei, Ruisong; Martin, Derek A; DiMarco, Diana M; Bolling, Bradley W

2017-05-24

Obesity is associated with increased risk for chronic diseases, and affects both developed and developing nations. Yogurt is a nutrient-dense food that may benefit individuals with lactose intolerance, constipation and diarrheal diseases, hypertension, cardiovascular diseases, diabetes, and certain types of cancer. Emerging evidence suggests that yogurt consumption might also improve the health of obese individuals. Obesity is often accompanied by chronic, low-grade inflammation perpetuated by adipose tissue and the gut. In the gut, obesity-associated dysregulation of microbiota and impaired gut barrier function may increase endotoxin exposure. Intestinal barrier function can be compromised by pathogens, inflammatory cytokines, endocannabinoids, diet, exercise, and gastrointestinal peptides. Yogurt consumption may improve gut health and reduce chronic inflammation by enhancing innate and adaptive immune responses, intestinal barrier function, lipid profiles, and by regulating appetite. While this evidence suggests that yogurt consumption is beneficial for obese individuals, randomized-controlled trials are needed to further support this hypothesis.

Overweight, Obesity and Weight Control

PubMed Central

Alexander, Marie M.; Stare, Fredrick J.

1967-01-01

Evidence is cited showing that overweight is a health hazard, but that this is primarily true only when the excess weight is due to an excess accumulation of adipose tissue. Diagnosis of frank obesity should be established by a careful interpretation of height-weight tables and of all other pertinent data. Although many factors play an etiologic role, obesity can occur only when caloric intake exceeds caloric output, and can be obviated only when this imbalance is reversed. Therefore prevention of weight gain, which should receive increasing attention, and also satisfactory weight loss, both require that caloric output be increased through added physical activity and that caloric intake be decreased through diminished consumption. Success depends on recognizing the fallacy of all misleading misinformation, and on establishing permanent habits of regular exercise and of moderation in eating and drinking. Suggestions are made that can be effective guidelines to a commonsense program of weight control. PMID:6045471

The weighty issue of obesity in paediatric respiratory medicine.

PubMed

Fitzgerald, Dominic A

2017-09-01

Some have observed that developed world is fat and getting fatter. This is even extending into the developing world, and it is important to appreciate that the consequences of childhood obesity last into adulthood and are associated with premature death. From the paediatric respiratory perspective, the deposition of excess adipose tissue in the thoraco-abdominal region begins early in life and is believed to alter diaphragm mobility and chest wall expansion, reduce lung compliance, and result in a rapid shallow breathing pattern with an increased work of breathing and reduction in maximum ventilatory capacity. This results in respiratory symptoms of exertional dyspnoea related to deconditioning which may present as exercise limitation, leading to confusion with common lung diseases such as asthma. The manifestations of the increasingly prevalent problems of overweight and obesity in young people and their interaction with common conditions of asthma and obstructive sleep apnoea will be discussed. Copyright © 2017. Published by Elsevier Ltd.

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes.

PubMed

Hooper, Philip L; Balogh, Gabor; Rivas, Eric; Kavanagh, Kylie; Vigh, Laszlo

2014-07-01

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease.

Inhibition of adipose tissue PPARγ prevents increased adipocyte expansion after lipectomy and exacerbates a glucose-intolerant phenotype.

PubMed

Booth, A D; Magnuson, A M; Cox-York, K A; Wei, Y; Wang, D; Pagliassotti, M J; Foster, M T

2017-04-01

Adipose tissue plays a fundamental role in glucose homeostasis. For example, fat removal (lipectomy, LipX) in lean mice, resulting in a compensatory 50% increase in total fat mass, is associated with significant improvement in glucose tolerance. This study was designed to further examine the link between fat removal, adipose tissue compensation and glucose homeostasis using a peroxisome proliferator-activated receptor γ (PPAR γ; activator of adipogenesis) knockout mouse. The study involved PPARγ knockout (FKOγ) or control mice (CON), subdivided into groups that received LipX or Sham surgery. We reasoned that as the ability of adipose tissue to expand in response to LipX would be compromised in FKOγ mice, so would improvements in glucose homeostasis. In CON mice, LipX increased total adipose depot mass (~60%), adipocyte number (~45%) and changed adipocyte distribution to smaller cells. Glucose tolerance was improved (~30%) in LipX CON mice compared to Shams. In FKOγ mice, LipX did not result in any significant changes in adipose depot mass, adipocyte number or distribution. LipX FKOγ mice were also characterized by reduction of glucose tolerance (~30%) compared to shams. Inhibition of adipose tissue PPARγ prevented LipX-induced increases in adipocyte expansion and produced a glucose-intolerant phenotype. These data support the notion that adipose tissue expansion is critical to maintain and/or improvement in glucose homeostasis. © 2016 John Wiley & Sons Ltd.

Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin.

PubMed

Ouadah-Boussouf, Nafia; Babin, Patrick J

2016-03-01

One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

PubMed

Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

2013-06-15

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

PubMed Central

Nohara, Kazunari; Waraich, Rizwana S.; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S.; Karsenty, Gérard; Burcelin, Rémy

2013-01-01

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension. PMID:23612996

The expression of cytokines and chemokines in the blood of patients with severe weight loss from anorexia nervosa: an exploratory study.

PubMed

Pisetsky, D S; Trace, S E; Brownley, K A; Hamer, R M; Zucker, N L; Roux-Lombard, P; Dayer, J-M; Bulik, C M

2014-09-01

Anorexia nervosa (AN) is a serious, potentially life-threatening disorder characterized by severe weight loss, dysregulated eating, and often excessive exercise. While psychiatric illnesses such as depression are associated with increased levels of pro-inflammatory mediators, evidence for such disturbances in patients with AN has been less clear. In an exploratory study of possible disturbances in immune responses in AN, we assayed a panel of cytokines and chemokines in the blood of patients undergoing inpatient treatment, testing the hypothesis that metabolic disturbances in this disease would lead to a pattern of immune disturbances distinct from that of other psychiatric diseases. For this purpose, we evaluated patients by the Beck Depression Inventory-II (BDI-II) and the Eating Disorders Examination-Questionnaire and assessed cytokines and chemokines by enzyme-linked immunosorbent assays. Patients reported a moderate level of depression (mean BDI-II = 22.6) but exhibited few immunologic abnormalities of the kind associated with major depressive disorder [e.g., increased interleukin (IL)-6]; RANTES showed the most frequent elevations and was increased in 4 of the patients studied. Together, these findings suggest that features of AN such as loss of adipose tissue and excessive exercise may attenuate cytokine production and thus modulate the experience of illness that impacts on core features of disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estrogen or raloxifene during postmenopausal weight loss: adiposity and cardiometabolic outcomes.

PubMed

Van Pelt, R E; Gozansky, W S; Wolfe, P; Kittelson, J M; Jankowski, C M; Schwartz, R S; Kohrt, W M

2014-04-01

Estrogen-based hormone therapy (HT) attenuates abdominal fat gain after menopause, but whether HT improves abdominal fat loss during weight loss is unknown. It was hypothesized that HT or a selective estrogen receptor modulator (raloxifene) would augment reductions in abdominal visceral fat during weight loss when compared to placebo, potentially increasing improvements in glucose tolerance and lipid profile. Healthy postmenopausal women (n = 119; age 50-70 yr) underwent a 6-month weight-loss (primarily exercise) intervention with randomization to raloxifene (60 mg/d), HT (conjugated estrogens, 0.625 mg/d), or placebo. Outcomes were change in total and abdominal (visceral and subcutaneous) fat mass, lipid profile, and fasting and post-challenge glucose and insulin. Neither HT nor raloxifene augmented loss of total or abdominal fat mass during exercise-induced weight loss when compared with placebo. Weight loss-induced improvements in risk factors were similar among the three groups, except for a greater reduction in fasted glucose in the HT group (difference in change [95%CI] from placebo; -0.40 [-0.76, -0.05]) and greater reductions in LDL (-0.36 [-0.63, -0.09]) and increases in HDL (0.15 [0.07, 0.24]) in both treatment groups. Postmenopausal HT and raloxifene did not increase abdominal fat loss during weight loss, but did improve some cardiometabolic outcomes. Copyright © 2013 The Obesity Society.

Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity

PubMed Central

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Zhang, Nan; Szweda, Luke I.; Griffin, Timothy M.; Barlic-Dicen, Jana

2014-01-01

The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.—Yao, L., Heuser-Baker, J., Herlea-Pana, O., Zhang, N., Szweda, L. I., Griffin, T. M., Barlic-Dicen, J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. PMID:25016030

Impact of weight loss with or without exercise on abdominal fat and insulin resistance in obese individuals: a randomised clinical trial.

PubMed

Trussardi Fayh, Ana Paula; Lopes, André Luiz; Fernandes, Pablo Rober; Reischak-Oliveira, Alvaro; Friedman, Rogério

2013-08-28

Evidence supports an important contribution of abdominal obesity and inflammation to the development of insulin resistance (IR) and CVD. Weight loss in obese individuals can reduce inflammation and, consequently, IR, but the role of training remains unclear. The aim of this study was to evaluate the effects of body weight reduction with and without exercise over abdominal fat tissue (primary outcome) and IR. In this randomised clinical trial, forty-eight obese individuals (age 31·8 (SD 6·0) years, BMI 34·8 (SD 2·7) kg/m2) were randomised to either a diet-only group (DI) or a diet and exercise group (DI þ EXE). Treatment was maintained until 5% of the initial body weight was lost. At baseline and upon completion, the following parameters were analysed: biochemical parameters such as glycaemia and insulin for the determination of homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP) and abdominal computed tomography for the determination of visceral and subcutaneous adipose tissue. A total of thirteen individuals dropped out before completing the weight-loss intervention and did not repeat the tests. In both the DI (n 18) and DI þ EXE (n 17) groups, we observed significant and similar decreases of visceral adipose tissue (difference between means: 7·9 (95% CI 29·5, 25·2) cm2, P¼0·36), hs-CRP (difference between means: 20·06 (95% CI 20·19, 0·03) mg/l, P¼0·39) and HOMA (difference between means: 20·04 (95% CI 20·17, 0·08), P¼0·53). In the present study, 5% weight loss reduced abdominal fat and IR in obese individuals and exercise did not add to the effect of weight loss on the outcome variables.

Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.

PubMed

Kawasaki, Noritaka; Asada, Rie; Saito, Atsushi; Kanemoto, Soshi; Imaizumi, Kazunori

2012-01-01

Adipose tissue plays a central role in maintaining metabolic homeostasis under normal conditions. Metabolic diseases such as obesity and type 2 diabetes are often accompanied by chronic inflammation and adipose tissue dysfunction. In this study, we observed that endoplasmic reticulum (ER) stress and the inflammatory response occurred in adipose tissue of mice fed a high-fat diet for a period of 16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic inflammation occurred in adipose tissue. We found that ER stress is induced by free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up-regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral administration to obese mice of chemical chaperons, which alleviate ER stress, improved chronic inflammation in adipose tissue, followed by the suppression of increased body weight and improved insulin signaling. These results indicate that ER stress plays important pathophysiological roles in obesity-induced adipose tissue dysfunction.

Contribution of Adipose Tissue to Development of Cancer

PubMed Central

Cozzo, Alyssa J.; Fuller, Ashley M.; Makowski, Liza

2018-01-01

Solid tumor growth and metastasis require the interaction of tumor cells with the surrounding tissue, leading to a view of tumors as tissue-level phenomena rather than exclusively cell-intrinsic anomalies. Due to the ubiquitous nature of adipose tissue, many types of solid tumors grow in proximate or direct contact with adipocytes and adipose-associated stromal and vascular components, such as fibroblasts and other connective tissue cells, stem and progenitor cells, endothelial cells, innate and adaptive immune cells, and extracellular signaling and matrix components. Excess adiposity in obesity both increases risk of cancer development and negatively influences prognosis in several cancer types, in part due to interaction with adipose tissue cell populations. Herein, we review the cellular and noncellular constituents of the adipose “organ,” and discuss the mechanisms by which these varied microenvironmental components contribute to tumor development, with special emphasis on obesity. Due to the prevalence of breast and prostate cancers in the United States, their close anatomical proximity to adipose tissue depots, and their complex epidemiologic associations with obesity, we particularly highlight research addressing the contribution of adipose tissue to the initiation and progression of these cancer types. Obesity dramatically modifies the adipose tissue microenvironment in numerous ways, including induction of fibrosis and angiogenesis, increased stem cell abundance, and expansion of proinflammatory immune cells. As many of these changes also resemble shifts observed within the tumor microenvironment, proximity to adipose tissue may present a hospitable environment to developing tumors, providing a critical link between adiposity and tumorigenesis. PMID:29357128

Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

PubMed Central

2012-01-01

Background Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. Methods Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. Results Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. Conclusions Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue. PMID:22974251

Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients.

PubMed

Jansen, Henry J; Vervoort, Gerald M; van der Graaf, Marinette; Stienstra, Rinke; Tack, Cees J

2013-11-01

Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content. To analyse associations between inflammatory features of the adipose tissue and liver fat content. A cross-sectional study. Twenty-seven obese patients with insulin-treated T2DM were studied. LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining. Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75-32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ≤5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively associated with LFAT. Several pro-inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin-treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation. © 2012 John Wiley & Sons Ltd.

Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum

PubMed Central

Teixeira, Luzia; Moreira, João; Melo, Joana; Bezerra, Filipa; Marques, Raquel M; Ferreirinha, Pedro; Correia, Alexandra; Monteiro, Mariana P; Ferreira, Paula G; Vilanova, Manuel

2015-01-01

The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet+ cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue. PMID:25581844

Role of Adiposity-Driven Inflammation in Depressive Morbidity

PubMed Central

Capuron, Lucile; Lasselin, Julie; Castanon, Nathalie

2017-01-01

Depression and metabolic disorders, including overweight and obesity, appear tightly interrelated. The prevalence of these conditions is concurrently growing worldwide, and both depression and overweight/obesity represent substantial risk factors for multiple medical complications. Moreover, there is now multiple evidence for a bidirectional relationship between depression and increased adiposity, with overweight/obesity being associated with an increased prevalence of depression, and in turn, depression augmenting the risk of weight gain and obesity. Although the reasons for this intricate link between depression and increased adiposity remain unclear, converging clinical and preclinical evidence points to a critical role for inflammatory processes and related alterations of brain functions. In support of this notion, increased adiposity leads to a chronic low-grade activation of inflammatory processes, which have been shown elsewhere to have a potent role in the pathophysiology of depression. It is therefore highly possible that adiposity-driven inflammation contributes to the development of depressive disorders and their growing prevalence worldwide. This review will present recent evidence in support of this hypothesis and will discuss the underlying mechanisms and potential therapeutic targets. Altogether, findings presented here should help to better understand the mechanisms linking adiposity to depression and facilitate the identification of new preventive and/or therapeutic strategies. PMID:27402495

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linde, B.; Hjemdahl, P.; Freyschuss, U.

Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilationmore » in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.« less

Longitudinal changes in objectively measured sedentary behaviour and their relationship with adiposity in children and adolescents: systematic review and evidence appraisal.

PubMed

Tanaka, C; Reilly, J J; Huang, W Y

2014-10-01

This review aimed to determine longitudinal changes in objectively measured overall sedentary behaviour, and to examine their associations with adiposity in children and adolescents. A search for longitudinal studies was performed using several electronic databases. Of 161 potentially eligible papers, 10 for change in sedentary behaviour and 3 for longitudinal associations with change in adiposity were included. Weighted mean increase in daily sedentary behaviour per year was 5.7% for boys and 5.8% for girls. Only one paper included preschool children, and it showed a decrease in sedentary behaviour. Nine studies were from Western countries. Null associations were reported between sedentary behaviour and adiposity in two studies, the other found that increases in sedentary behaviour were associated with increases in adiposity, but only in those with body mass index above the 50th percentile. There was consistent evidence that sedentary behaviour increases with age in school-age children and adolescents, by approximately 30 min extra daily sedentary behaviour per year. There was little evidence on the influence of changes in sedentary behaviour on changes in adiposity. There is a need for more longitudinal research, for more evidence from outside the Western world, and for more studies that examine 'dose-response' associations between changes in sedentary behaviour and changes in adiposity. © 2014 The Author(s). obesity reviews © 2014 World Obesity.

CELL BIOLOGY SYMPOSIUM: Practical application of the basic aspects of GLUT4 membrane trafficking and insulin signaling on issues related to animal agriculture.

PubMed

Smith, S B

2017-05-01

Because of the relatively short lifespans of beef cattle, membrane trafficking in relation to inflammation is not considered important unless it overtly affects productivity. However, glucose uptake and utilization is important for adipose tissue development in beef cattle, and increasing glucose utilization in intramuscular adipose tissue can increase carcass quality. Research from the 1980s demonstrated a lack of insulin sensitivity in isolated bovine adipocytes and adipose tissue explants incubated in vitro. Insulin did not stimulate glucose or acetate incorporation into fatty acids, nor did it increase concentrations of glycolytic intermediates in bovine adipose tissue incubated with exogenous glucose. Specific binding of [I] iodoinsulin and insulin degradation in bovine isolated adipocytes was low to non-detectable. These early studies indicated that insulin-dependent receptor-mediated signaling was less important in bovine adipose tissue than in adipose tissues of humans, swine, or laboratory species. More recent research demonstrated that glucose transporter protein 4 (GLUT4) expression in muscle and adipose tissue declines markedly after birth in calves, indicating the development of insulin resistance as cattle transition from suckling to functional ruminants. Insulin resistance is important in dairy cattle, causing ketosis and fatty liver. Consistent with this, subcutaneous adipose tissue expression decreases 50% following parturition in dairy cattle, although expression of genes associated with insulin responsiveness (, , and ) is up-regulated by 21 d postpartum. Understanding the underlying mechanisms of insulin resistance in beef and dairy cattle would increase animal health and thereby improve productivity.

Regulation of adiposity by mTORC1

PubMed Central

Magdalon, Juliana; Festuccia, William Tadeu

2017-01-01

ABSTRACT Obesity is characterized by an excessive increase in the adipose tissue mass, and is associated with higher incidence of several chronic metabolic diseases, such as type 2 diabetes. Therefore, its increasing prevalence is a public health concern, and it is important to better understand its etiology to develop new therapeutic strategies. Evidence accumulated over the years indicates that obesity is associated with a marked activation in adipose tissue of the mechanistic target of rapamycin complex 1 (mTORC1), a signaling pathway that controls lipid metabolism, and adipocyte formation and maintenance. Curiously, mTORC1 is also involved in the control of nonshivering thermogenesis and recruitment as well as browning of white adipose tissue. In this review, we explored mTORC1 functions in adipocytes and presented evidence, suggesting that mTORC1 may either increase or reduce adiposity, depending on the conditions and activation levels. PMID:29364369

Intermittent cold exposure enhances fat accumulation in mice.

PubMed

Yoo, Hyung Sun; Qiao, Liping; Bosco, Chris; Leong, Lok-Hei; Lytle, Nikki; Feng, Gen-Sheng; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis.

Intermittent Cold Exposure Enhances Fat Accumulation in Mice

PubMed Central

Yoo, Hyung sun; Qiao, Liping; Bosco, Chris; Leong, Lok-Hei; Lytle, Nikki; Feng, Gen-Sheng; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis. PMID:24789228

Visceral adiposity index as a predictor of clinical severity and therapeutic outcome of PCOS.

PubMed

Zheng, Sai-Hua; Li, Xue-Lian

2016-01-01

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disease which often accompany with abnormal fat distribution. Visceral adiposity has association with abnormal lipid metabolic, pro-inflammatory activity, insulin resistance (IR) and hyperandrogenism. Increased visceral adiposity raises the risk of metabolic syndrome, type 2 diabetes and cardiovascular (CV) events, and aggravates ovulatory dysfunction and hyperandrogenism in PCOS women. Visceral adiposity index (VAI), a simple surrogate maker of visceral adipose dysfunction and visceral adiposity, is a predictor of IR, and link hyperinsulinemia, hyperandrogenism and anovulation. This review aims to discuss the visceral adiposity situation in PCOS women, and suggests that VAI may be a useful predictor of clinical severity and therapeutic outcome of PCOS.

Immediate and long-term effects of addition of exercise to a 16-week very low calorie diet on low-grade inflammation in obese, insulin-dependent type 2 diabetic patients.

PubMed

Snel, Marieke; van Diepen, Janna A; Stijnen, Theo; Pijl, Hanno; Romijn, Johannes A; Meinders, A E; Voshol, Peter; Jazet, Ingrid M

2011-12-01

To assess the short- and long-term effects of addition of exercise to a very low calorie diet (VLCD) on low-grade inflammation in obese patients with type 2 diabetes mellitus (T2DM). Twenty seven obese, insulin-dependent T2DM patients followed a 4-month VLCD with (n=13) or without (n=14) exercise and were followed up to 18 months. Anthropometric measurements, metabolic and inflammatory parameters were assessed before, directly after the intervention and at 6 and 18 months follow-up. The same measurements were performed only once in 56 healthy lean and 56 healthy obese controls. At baseline hsCRP, IL10 and IL8 were significantly elevated in obese T2DM compared to lean healthy controls. After 4 months, despite substantial weight loss (-25.4 ± 1.3 kg), neither the VLCD nor VLCD+exercise had an effect on plasma cytokines. At 6 months, in the weight-stabilizing period, measures of low-grade inflammation had decreased substantially and equally in both intervention groups. Despite subsequent weight regain, beneficial effect was sustained up to 18 months in both groups, except for IL1 and hsCRP which had returned to baseline in the VLCD-only group. Our findings suggest that severe caloric restriction increases cytokine production by adipose tissue macrophages and that the beneficial effects of weight loss become apparent only in the eucaloric state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ontogenesis of muscle and adipose tissues and their interactions in ruminants and other species.

PubMed

Bonnet, M; Cassar-Malek, I; Chilliard, Y; Picard, B

2010-07-01

The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This competition or prioritization occurs through cellular signalling pathways and the secretion of proteins by adipose tissue (adipokines) and muscle (myokines), putatively regulating their hypertrophy in a reciprocal manner. Further work on the mechanisms underlying cross-talk between brown or white adipocytes and muscle fibres will help to achieve better understanding as a prerequisite to improving the control of body growth and composition in cattle.

The Association of Adiposity Indices and Plasma Vitamin D in Young Females in Saudi Arabia

PubMed Central

2016-01-01

Background. Vitamin D deficiency is a global health problem. Some evidences indicate its association with metabolic syndrome, type II diabetes, and cardiovascular diseases. In the current study we aim to study the association of vitamin D level and indicators of adiposity in young Saudi females. Subjects and Methods. 87 young healthy Saudi females were recruited from University of Dammam, Dammam, Saudi Arabia. Each subject filled vitamin D questionnaire and had exercise stress test to determine VO2 peak. Body weight, BMI, waist and hip circumference, and ratios were determined. Blood was analyzed for 25-OH vitamin D, glucose, triglycerides, total cholesterol, and differential cholesterol. Results. 25-OH vitamin D/body weight was negatively associated with waist circumference and waist/stature ratio. No significant difference was found between the groups of BMI with regard to the data of questionnaire or 25-OH vitamin D/body weight. Obese and overweight subjects had lower VO2 peak. Conclusion. In young Saudi females we found that the relative value of vitamin D to body weight is a better indicator of vitamin D status particularly in obese subjects and it is negatively associated with adiposity measures of waist circumference and waist/stature ratio. PMID:27525007

Differential effect of subcutaneous abdominal and visceral adipose tissue on cardiometabolic risk.

PubMed

Sam, Susan

2018-03-09

Metabolic and cardiovascular diseases are increasing worldwide due to the rise in the obesity epidemic. The metabolic consequences of obesity vary by distribution of adipose tissue. Visceral and ectopic adipose accumulation are associated with adverse cardiometabolic consequences, while gluteal-femoral adipose accumulation are negatively associated with these adverse complications and subcutaneous abdominal adipose accumulation is more neutral in its associations. Gender, race and ethnic differences in adipose tissue distribution have been described and could account for the observed differences in risk for cardiometabolic disease. The mechanisms behind the differential impact of adipose tissue on cardiometabolic risk have started to be unraveled and include differences in adipocyte biology, inflammatory profile, connection to systemic circulation and most importantly the inability of the subcutaneous adipose tissue to expand in response to positive energy balance.

Ketoconazole, an antifungal agent, protects against adiposity induced by a cafeteria diet.

PubMed

Campión, J; Martínez, J A

2004-07-01

Ketoconazole, an anti-glucocorticoid agent, is widely used in humans as an antifungal agent. It inhibits ergosterol synthesis and reduces cortisol levels in the treatment of Cushing's Syndrome. The aim of this work was to study the drug's preventive potential against adiposity induced by a high-fat cafeteria diet in rats. Female Wistar rats were fed on standard pelleted diet or cafeteria diet during 42 days in the presence or absence of an oral treatment with ketoconazole (24 mg/kg of body weight). The cafeteria diet increased energy intake and body weight. In addition, this high-fat diet increased body-fat weight and adipose tissue depots analyzed. Interestingly, ketoconazole was able to protect against increased total body fat and adipose depot enlargement induced after cafeteria-diet feeding. Moreover, ex vivo isoproterenol-induced lipolysis was reduced in adipocytes from cafeteria-fed animals; this decrease was reverted by treatment with ketoconazole. Thus, ketoconazole was able to protect against adiposity induced by a cafeteria diet, revealing an interaction between fat intake and glucocorticoids on adipose deposition.

The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Suyeon; Soltani-Bejnood, Morvarid; Quignard-Boulange, Annie

2006-07-01

BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO),more » and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.« less

Physical training in the prophylaxis and treatment of obesity, hypertension and diabetes.

PubMed

Krotkiewski, M

1983-01-01

The results of physical training in 600 obese and 100 diabetic patients are described and discussed. Three months of physical training (55 min 3 times/week) without dietary restriction did not result in any change in body weight and composition either in obese or diabetic female patients. However, the male patients remained their body weight unchanged and body fat decreased and lean body mass increased after training. The combination of exercise with a very low calorie diet in obese women neither prevents the erosion of lean body mass nor the diet-induced decrease in oxygen uptake. Local exercise could not evoke a local decrease in the thickness of adipose tissue. The addition of physical training to the low calorie diet leads to better social and psychological compliance and a more equal distribution of adipose tissue. A close relationship has been found between the muscle morphology and glucose metabolism in obese patients. Insulin concentration appeared to be positively correlated to the percentage of FTb fibers and inversely correlated to the capillary density. The decrease in the percentage of FTb muscle fibers and the increase in the number of capillaries were correlated to the decrease in plasma insulin levels. The capillary density appeared to be reduced with decreasing degrees of glucose tolerance. In patients with diabetes type I it was found diminished so much that the diffusion distance in muscle increased after training. The most interesting results related to glucose metabolism were found otherwise as follows: The sum of insulin (276.4 +/- 20.1 before and 255.1 +/- 19.0 after p less than 0.05) and glucose levels (but not fasting values) decreased (28.3 +/- 1.6 before and 27.8 +/- 1.4 after p less than 0.01) after training in obesity. In obese and diabetic patients with initially high insulin values physical training resulted in a decrease in insulin level, while in those patients with initially low values it resulted in an increase. As judged from the insulin C-peptide ratio, patients who decreased their insulin levels after training increased their liver uptake of insulin. The increased hepatic extraction of insulin without the decrease of insulin production was also noted in patients with diabetes type II. After training both obese patients and those with diabetes I and II increased their glucose metabolism (disposal rate) during insulin euglycemic clamp. Patients with diabetes type II showed initially lower basal and insulin-stimulated glucose incorporation into triglycerides.(ABSTRACT TRUNCATED AT 400 WORDS)

The aging musculoskeletal system and obesity-related considerations with exercise.

PubMed

Vincent, Heather K; Raiser, Sara N; Vincent, Kevin R

2012-07-01

Advancing age and adiposity contribute to musculoskeletal degenerative diseases and the development of sarcopenic obesity. The etiology of muscle loss is multifactorial, and includes inflammation, oxidative stress and hormonal changes, and is worsened by activity avoidance due to fear of pain. The risk for mobility disability and functional impairment rises with severity of obesity in the older adult. Performance measures of walking distance, walking speed, chair rise, stair climb, body transfers and ability to navigate obstacles on a course are adversely affected in this population, and this reflects decline in daily physical functioning. Exercise training is an ideal intervention to counteract the effects of aging and obesity. The 18 randomized controlled trials of exercise studies with or without diet components reviewed here indicate that 3-18 month programs that included aerobic and strengthening exercise (2-3 days per week) with caloric restriction (typically 750 kcal deficit/day), induced the greatest change in functional performance measures compared with exercise or diet alone. Importantly, resistance exercise attenuates muscle mass loss with the interventions. These interventions can also combat factors that invoke sarcopenia, including inflammation, oxidative stress and insulin resistance. Therefore, regular multimodal exercise coupled with diet appears to be very effective for counteracting sarocpenic obesity and improving mobility and function in the older, obese adult. Copyright © 2012 Elsevier B.V. All rights reserved.

Ethnic influences on the relations between abdominal subcutaneous and visceral adiposity, liver fat, and cardiometabolic risk profile: the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity.

PubMed

Nazare, Julie-Anne; Smith, Jessica D; Borel, Anne-Laure; Haffner, Steven M; Balkau, Beverley; Ross, Robert; Massien, Christine; Alméras, Natalie; Després, Jean-Pierre

2012-10-01

Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution. We aimed to identify differences across ethnic groups in interrelations between BMI, abdominal adiposity, liver fat, and CMR profile. In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured. Higher ranges of BMI were associated with higher levels of visceral [visceral adipose tissue (VAT)] and deep subcutaneous [deep subcutaneous adipose tissue (DSAT)] adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration. Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.

Aerobic Exercise Modulates the Free Fatty Acids and Inflammatory Response During Obesity and Cancer Cachexia.

PubMed

Teixeira, Alexandre Abilio de Souza; Lira, Fábio Santos; Pimentel, Gustavo D; Oliveira de Souza, Camila; Batatinha, Helena; Biondo, Luana A; Yamashita, Alex S; Junior, Edson A Lima; Neto, José Cesar Rosa

2016-01-01

White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

[The effect of a single moderate physical exertion on serum leptin levels in patients with essential hypertension (preliminary results)].

PubMed

Zyśko, D; Gajek, J; Jołda-Mydłowska, B

2000-08-01

Leptin is a product of the ob gene and is secreted by the adipose tissue. It takes part in regulation of nervous, cardiovascular, endocrine system and renal functions. The aim of this study was to assess the influence of short term moderate exercise on serum leptin levels in patients with arterial hypertension. The study group consisted of 34 patients with essential hypertension: 15 women (48.9 +/- 12.1 years old) and 19 men (43.5 +/- 14.6 years old). There were 7 patients with stage I of hypertension, 17 patients with stage II of hypertension and 10 patients with stage III of hypertension. The blood samples were taken before and after the exercise test. Serum leptin levels were assessed by radioimmunoassay. Serum leptin levels were significantly higher in women then in men. The logarithm of serum leptin levels after the exercise was significantly lower than before (0.8 +/- 0.4 and 0.9 +/- 0.5 respectively). The moderate, short term exercise decreases serum leptin levels in the hypertensive patients.

Abdominal obesity and metabolic syndrome: exercise as medicine?

PubMed

Paley, Carole A; Johnson, Mark I

2018-01-01

Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

Ghrelin receptor regulates adipose tissue inflammation in aging.

PubMed

Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

2016-01-01

Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

Ghrelin receptor regulates adipose tissue inflammation in aging

PubMed Central

Buras, Eric D.; Yu, Kaijiang; Wang, Ruitao; Smith, C. Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

2016-01-01

Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr−/− mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr−/− mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsr−/− mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID:26837433

Effect of n-3 fatty acids on free tryptophan and exercise fatigue.

PubMed

Huffman, Derek M; Altena, Thomas S; Mawhinney, Thomas P; Thomas, Tom R

2004-08-01

Free tryptophan (Trp), which is augmented by liberated free fatty acids (FFA) from adipose tissue, can induce mental fatigue via serotonin during exercise. Since an attenuation in FFA has been observed with omega-3 fatty acid (n-3fa) use, our purpose was to examine the effect of n-3fa supplementation on free Trp availability and exercise fatigue. Ten recreationally trained men ( n=5) and women ( n=5), with maximal oxygen consumption (VO(2max))of 51.6 (3.0) and 44.3 (1.4) ml kg(-1) min(-1), respectively, were studied on two occasions following an overnight fast, before and after n-3fa supplementation (4 g day(-1) for 4 weeks). The exercise trials consisted of a 75-min treadmill run at 60% VO(2max) followed immediately by a high-intensity incremental bout to fatigue. Measurements included exercise monitors, plasma volume (PV), triglycerides (TG), FFA, glycerol, lactate, and glucose. Free Trp and branched-chain amino acids (BCAA) were measured and correlated with time to fatigue; all blood variables were corrected for PV. Free Trp, lactate, glucose, FFA, and glycerol were not significantly different between trials, but TG ( P<0.001) and the free Trp/BCAA ratio were significantly lower after n-3fa use [1.76 (0.18)x10(-2) microg ml(-1)] versus before supplementation [2.17 (0.22), P=0.033]. There was a non-significant increase in time to fatigue after supplementation [10.2 (0.3) min] versus before n-3fa use [9.7 (0.2), P=0.068], and a tendency for higher BCAA levels after supplementation, P=0.068. However, neither free Trp nor the free Trp/BCAA ratio significantly predicted time to fatigue. In conclusion, n-3fa supplementation did not diminish free Trp concentrations or significantly improve endurance performance during a maximal bout of exercise.

Body mass index kinetics around adiposity rebound in Anorexia nervosa: A case-control study.

PubMed

Neveu, Rémi; Neveu, Dorine; Carrier, Edouard; Ourrad, Nadia; Perroud, Alain; Nicolas, Alain

2016-10-01

Anorexia nervosa (AN) is associated with parameters involved in body mass index (BMI) regulation. Contrary to obesity, BMI kinetics around the adiposity rebound is not documented in AN. This study aimed at investigating which characteristics of BMI kinetics around the adiposity rebound are associated with AN. Multicentre case-control study with 101 inpatient women with AN onset after 10 years of age, and 101 healthy women, all free of overweight history and matched for age, level of education and fathers' socio-professional status. Age at adiposity rebound, pre- and post-adiposity rebound BMI velocities and accelerations (change in velocity over time) were estimated with linear mixed models using data recorded between 2 and 10 years of age. Patients had an earlier adiposity rebound (mean (standard deviation (SD)): 5.3 (1.3) vs 5.7 (1.1) years), a larger BMI at adiposity rebound (mean (SD): 15.3 [1] vs 14.9 (0.9) kg/m 2 ) and 29% lower BMI acceleration after adiposity rebound than controls. After adjustment, only BMI at adiposity rebound and BMI acceleration after adiposity rebound were associated with a higher risk of AN (Odds ratio [95% confidence interval]: 2.15 [1.41-3.46] for an increase of 1 kg/m 2 and 2.44 [1.56-4.02] for an increase of 0.1 kg/(m 2 *years 2 ) respectively). These two factors were not correlated in patients (r = 0.007, p = 0.96). A flattened evolution of BMI after adiposity rebound and higher BMI at adiposity rebound were associated with AN. Further prospective study is needed to confirm these findings. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study).

PubMed

Davillas, Apostolos; Benzeval, Michaela; Kumari, Meena

2016-01-01

Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to 50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years.

Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study)

PubMed Central

2016-01-01

Background Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. Objective To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Methods Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Results Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. Conclusions We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years. PMID:26849046

Nutritional and metabolic determinants of blood rheology differ between trained and sedentary individuals.

PubMed

Varlet-Marie, Emmanuelle; Guiraudou, Marie; Fédou, Christine; Raynaud de Mauverger, Eric; Durand, Fabienne; Brun, Jean-Frédéric

2013-01-01

Body composition and nutrition have been reported to be correlated with blood rheology. However, in sedentary and in physically active individuals these relationships seem to be not exactly similar. This study investigated whether exercise training status influences these relationships. 32 athletes (ATH) (age: 25 ± 0.7 yr; body mass index (BMI): 23.75 ± 0.23 kg/m2) were compared to 21 sedentary subjects (SED) (age: 45.19 ± 2.90; BMI = 33.41 ± 1.33) with nutritional assessment (autoquestionnaire), bioelectrical impedancemetry, viscometry at high shear rate (MT90) and Myrenne aggregometer. Subjects differ according to age, weight and adiposity parameters. Their eating behavior is different: ATH eat a higher percentage of protein (p < 0.005), a lower percentage of lipid (p < 0.05), and a higher total amount of carbohydrate (+31% p < 0.02). Their viscosity factors are similar except plasma viscosity which is higher in SED than ATH (1.51 ± 0.03 vs 1.43 ± 0.02 mPa.s, p < 0.05). In both ATH and SED, abdominal obesity (waist-to-hip ratio or WHR) is associated with impairments in blood rheology, but not exactly the same. In ATH, WHR is associated with an increase in hematocrit (r = 0.647; p = 0.009), plasma viscosity (r = 0.723; p = 0.002), and caloric (and CHO) intake moderately increase RBC rigidity (r = 0.5405; p = 0.0251) and aggregability (r = 0.3366 p = 0.0596). In SED the picture is different, adiposity increases hematocrit (r = 0.460; p = 0.048), abdominal fatness increases blood viscosity independent of hematocrit, and CHO intake is associated with lower RBC aggregability (r = -0.493; p = 0.0319).

Effects of pistachio nuts on body composition, metabolic, inflammatory and oxidative stress parameters in Asian Indians with metabolic syndrome: a 24-wk, randomized control trial.

PubMed

Gulati, Seema; Misra, Anoop; Pandey, Ravindra Mohan; Bhatt, Surya Prakash; Saluja, Shelza

2014-02-01

The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P < 0.02), FBG (P < 0.04), total cholesterol (P < 0.02), low-density lipoprotein cholesterol (P < 0.006), hs-CRP (P < 0.05), TNF-α (P < 0.03), FFAs (P < 0.001), TBARS (P < 0.01), and adiponectin levels (P < 0.001). A single food intervention with pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences between sexes in rectal cooling rates after exercise-induced hyperthermia.

PubMed

Lemire, Bruno B; Gagnon, Daniel; Jay, Ollie; Kenny, Glen P

2009-08-01

We evaluated differences between sexes in core cooling rates during cold water immersion after exercise-induced hyperthermia. Ten male (M) and nine female (F) participants, matched for body surface area-to-mass ratio (AD/M) (F: 268 +/- 19 vs M: 261 +/- 16 cm2 x kg(-1)), were recruited for the study. Participants exercised until rectal temperature reached 39.5 degrees C and were subsequently immersed in a 2.0 degrees C circulated water bath until rectal temperature decreased to 37.5 degrees C. Rectal and mean skin temperatures and the relative rate of nonevaporative heat loss (W x m(-2)) were measured continuously during the immersion period. Males were heavier, had a lower body fat percentage, and had a greater amount of lean body mass compared with females (P < or = 0.05). Significant differences were found in the overall cooling rate for rectal temperature (F: 0.22 +/- 0.07 vs M: 0.12 +/- 0.03 degrees C x min(-1), P = 0.001) and in the overall immersion times (F: 10.89 +/- 4.49 vs M: 18.13 +/- 4.47 min, P = 0.003). Mean skin temperature was lower in females compared with that in males during the immersion period (P < 0.001), although there were no differences between sexes in the rate of nonevaporative heat loss (P = 0.180). Although females had a similar AD/M and greater body adiposity, they had approximately 1.7-fold greater rectal cooling rate. Because AD/M and body adiposity do not seem to influence rectal cooling rates in previously hyperthermic individuals, the greater cooling rates in females may be attributed to physical differences in lean body mass.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

PubMed

Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Lifecourse Childhood Adiposity Trajectories Associated With Adolescent Insulin Resistance

PubMed Central

Huang, Rae-Chi; de Klerk, Nicholas H.; Smith, Anne; Kendall, Garth E.; Landau, Louis I.; Mori, Trevor A.; Newnham, John P.; Stanley, Fiona J.; Oddy, Wendy H.; Hands, Beth; Beilin, Lawrence J.

2011-01-01

OBJECTIVE In light of the obesity epidemic, we aimed to characterize novel childhood adiposity trajectories from birth to age 14 years and to determine their relation to adolescent insulin resistance. RESEARCH DESIGN AND METHODS A total of 1,197 Australian children with cardiovascular/metabolic profiling at age 14 years were studied serially from birth to age 14 years. Semiparametric mixture modeling was applied to anthropometric data over eight time points to generate adiposity trajectories of z scores (weight-for-height and BMI). Fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were compared at age 14 years between adiposity trajectories. RESULTS Seven adiposity trajectories were identified. Three (two rising and one chronic high adiposity) trajectories comprised 32% of the population and were associated with significantly higher fasting insulin and HOMA-IR compared with a reference trajectory group (with longitudinal adiposity z scores of approximately zero). There was a significant sex by trajectory group interaction (P < 0.001). Girls within a rising trajectory from low to moderate adiposity did not show increased insulin resistance. Maternal obesity, excessive weight gain during pregnancy, and gestational diabetes were more prevalent in the chronic high adiposity trajectory. CONCLUSIONS A range of childhood adiposity trajectories exist. The greatest insulin resistance at age 14 years is seen in those with increasing trajectories regardless of birth weight and in high birth weight infants whose adiposity remains high. Public health professionals should urgently target both excessive weight gain in early childhood across all birth weights and maternal obesity and excessive weight gain during pregnancy. PMID:21378216

Association of Changes in Abdominal Fat Quantity and Quality With Incident Cardiovascular Disease Risk Factors.

PubMed

Lee, Jane J; Pedley, Alison; Hoffmann, Udo; Massaro, Joseph M; Fox, Caroline S

2016-10-04

Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are associated with adverse cardiometabolic risk profiles. This study explored the degree to which changes in abdominal fat quantity and quality are associated with changes in cardiovascular disease (CVD) risk factors. Study participants (n = 1,106; 44.1% women; mean baseline age 45.1 years) were drawn from the Framingham Heart Study Third Generation cohort who participated in the computed tomography (CT) substudy Exams 1 and 2. Participants were followed for 6.1 years on average. Abdominal adipose tissue volume in cm(3) and attenuation in Hounsfield units (HU) were determined by CT-acquired abdominal scans. The mean fat volume change was an increase of 602 cm(3) for SAT and an increase of 703 cm(3) for VAT; the mean fat attenuation change was a decrease of 5.5 HU for SAT and an increase of 0.07 HU for VAT. An increase in fat volume and decrease in fat attenuation were associated with adverse changes in CVD risk factors. An additional 500 cm(3) increase in fat volume was associated with incident hypertension (odds ratio [OR]: 1.21 for SAT; OR: 1.30 for VAT), hypertriglyceridemia (OR: 1.15 for SAT; OR: 1.56 for VAT), and metabolic syndrome (OR: 1.43 for SAT; OR: 1.82 for VAT; all p < 0.05). Similar trends were observed for each additional 5 HU decrease in abdominal adipose tissue attenuation. Most associations remained significant even after further accounting for body mass index change, waist circumference change, or respective abdominal adipose tissue volumes. Increasing accumulation of fat quantity and decreasing fat attenuation are associated with worsening of CVD risk factors beyond the associations with generalized adiposity, central adiposity, or respective adipose tissue volumes. Published by Elsevier Inc.

Effect of Chronic Athletic Activity on Brown Fat in Young Women.

PubMed

Singhal, Vibha; Maffazioli, Giovana D; Ackerman, Kate E; Lee, Hang; Elia, Elisa F; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M; Misra, Madhusmita

2016-01-01

The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18-25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Our study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit.

A path model of sarcopenia on bone mass loss in elderly subjects.

PubMed

Rondanelli, M; Guido, D; Opizzi, A; Faliva, M A; Perna, S; Grassi, M

2014-01-01

Aging is associated with decreases in muscle mass, strength, power (sarcopenia) and bone mineral density (BMD). The aims of this study were to investigate in elderly the role of sarcopenia on BMD loss by a path model, including adiposity, inflammation, and malnutrition associations. Body composition and BMD were measured by dual X-ray absorptiometry in 159 elderly subjects (52 male/107 female; mean age 80.3 yrs). Muscle strength was determined with dynamometer. Serum albumin and PCR were also assessed. Structural equations examined the effect of sarcopenia (measured by Relative Skeletal Muscle Mass, Total Muscle Mass, Handgrip, Muscle Quality Score) on osteoporosis (measured by Vertebral and Femoral T-scores) in a latent variable model including adiposity (measured by Total Fat Mass, BMI, Ginoid/Android Fat), inflammation (PCR), and malnutrition (serum albumin). The sarcopenia assumed a role of moderator in the adiposity-osteoporosis relationship. Specifically, increasing the sarcopenia, the relationship adiposity-osteoporosis (β: -0.58) decrease in intensity. Adiposity also influences sarcopenia (β: -0.18). Malnutrition affects the inflammatory and the adiposity states (β: +0.61, and β: -0.30, respectively), while not influencing the sarcopenia. Thus, adiposity has a role as a mediator of the effect of malnutrition on both sarcopenia and osteoporosis. Malnutrition decreases adiposity; decreasing adiposity, in turn, increase the sarcopenia and osteoporosis. This study suggests such as in a group of elderly sarcopenia affects the link between adiposity and BMD, but not have a pure independent effect on osteoporosis.

A cluster randomized controlled trial for child and parent weight management: children and parents randomized to the intervention group have correlated changes in adiposity.

PubMed

Berry, Diane C; McMurray, Robert G; Schwartz, Todd A; Hall, Emily G; Neal, Madeline N; Adatorwover, Reuben

2017-01-01

Studies have suggested that obesity is linked within families and that successful interventions involve both the parent and child with obesity. However little information exists regarding similarities in adiposity and weight loss between the parent and child, especially in low socio-economic ethnically diverse households. The purpose of this study was to examine the relationships between the changes from baseline over time in adiposity, weight, health behaviors, and self-efficacy in children ( n  = 184) and parents ( n  = 184) participating in an 18-month weight loss program. Within the intervention group only and for each post-baseline time point, Pearson correlation coefficients were computed for children's changes (from baseline) in adiposity, weight, health behaviors, and self-efficacy, with their parents' corresponding changes from baseline, to determine how strongly the dyads were correlated. At the completion of 18 months, the intervention group parents demonstrated strong positive correlations between parent and child change in waist circumference ( r  = 0.409, p  < 0.001), triceps ( r  = 0.332, p  < 0.001), and subscapular ( r  = 0.292, p  = 0.002) skinfolds. There were no significant correlations between weight, health behaviors, eating, and exercise self-efficacy. The results suggest that in the Southern United States low-income parents and their children with obesity are strongly correlated. NCT01378806 Retrospectively Registered on June 22, 2011.

Liver but not adipose tissue is responsive to the pattern of enteral feeding

PubMed Central

Otero, Yolanda F.; Lundblad, Tammy M.; Ford, Eric A.; House, Lawrence M.; McGuinness, Owen P.

2014-01-01

Abstract Nutritional support is an important aspect of medical care, providing calories to patients with compromised nutrient intake. Metabolism has a diurnal pattern, responding to the light cycle and food intake, which in turn can drive changes in liver and adipose tissue metabolism. In this study, we assessed the response of liver and white adipose tissue (WAT) to different feeding patterns under nutritional support (total enteral nutrition or TEN). Mice received continuous isocaloric TEN for 10 days or equal calories of chow once a day (Ch). TEN was given either at a constant (CN, same infusion rate during 24 h) or variable rate (VN, 80% of calories fed at night, 20% at day). Hepatic lipogenesis and carbohydrate‐responsive element‐binding protein (ChREBP) expression increased in parallel with the diurnal feeding pattern. Relative to Ch, both patterns of enteral feeding increased adiposity. This increase was not associated with enhanced lipogenic gene expression in WAT; moreover, lipogenesis was unaffected by the feeding pattern. Surprisingly, leptin and adiponectin expression increased. Moreover, nutritional support markedly increased hepatic and adipose FGF21 expression in CN and VN, despite being considered a fasting hormone. In summary, liver but not WAT, respond to the pattern of feeding. While hepatic lipid metabolism adapts to the pattern of nutrient availability, WAT does not. Moreover, sustained delivery of nutrients in an isocaloric diet can cause adiposity without the proinflammatory state observed in hypercaloric feeding. Thus, the liver but not adipose tissue is responsive to the pattern of feeding behavior. PMID:24744913

Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy.

PubMed

de Castro, J; Sevillano, J; Marciniak, J; Rodriguez, R; González-Martín, C; Viana, M; Eun-suk, O H; de Mouzon, S Hauguel; Herrera, E; Ramos, M P

2011-11-01

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance.

PubMed

Palanivel, R; Fullerton, M D; Galic, S; Honeyman, J; Hewitt, K A; Jorgensen, S B; Steinberg, G R

2012-11-01

Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known. We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed. The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1). These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.

Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini.

PubMed

McMenamin, Sarah K; Minchin, James E N; Gordon, Tiffany N; Rawls, John F; Parichy, David M

2013-04-01

Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity.

Dwarfism and Increased Adiposity in the gh1 Mutant Zebrafish vizzini

PubMed Central

McMenamin, Sarah K.; Minchin, James E.N.; Gordon, Tiffany N.

2013-01-01

Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity. PMID:23456361

Adipose tissue in myocardial infarction.

PubMed

Su, Leon; Siegel, John E; Fishbein, Michael C

2004-01-01

The histologic evolution of myocardial infarction (MI) has been studied in some detail. However, there is little mention of the presence of adipose tissue in healed MI(HMI). Ninety-one hearts explanted during 1997-2001 were examined to determine the extent of adipose tissue within HMI. The medical records, surgical pathology reports, and all histologic sections of the explanted heart, from patients undergoing heart transplantation for ischemic heart disease, were reviewed. Adipose tissue within the areas of HMI was quantified. The location of the HMI, the age and gender of the patient, age of HMI, and whether the patient was treated with coronary artery bypass surgery (CABG) were noted. Of the 91 hearts examined, 168 HMIs were identified; 141 (84%) contained some mature fat within the HMI. Adipose tissue increased with increasing age, in males, and in those patients who had CABG surgery. The amount of adipose tissue was not related to the location or age of the HMI. Adipose tissue is a prevalent histological finding in HMIs. The pathogenesis of adipose tissue is unknown, but may be influenced by current medical therapy for ischemic heart disease, thus explaining why adipose tissue in HMIs was not reported until 1997. The presence of fat supports the speculation that a regenerative cell, or multipotent stem cell, exists within the heart, and under the influence of microenvironmental or therapeutic factors can differentiate into fat, other mesenchymal tissues, and potentially even myocardium.

Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

PubMed Central

Paniagua, Juan Antonio

2016-01-01

Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS. PMID:27895819

The effect of dietary carbohydrate on genes for fatty acid synthase and inflammatory cytokines in adipose tissues from lean and obese subjects.

PubMed

Hudgins, Lisa C; Baday, Aline; Hellerstein, Marc K; Parker, Thomas S; Levine, Daniel M; Seidman, Cynthia E; Neese, Richard A; Tremaroli, Jolanta D; Hirsch, Jules

2008-04-01

Hepatic de novo lipogenesis (DNL) is markedly stimulated in humans by low-fat diets enriched in simple sugars. However, the dietary responsiveness of the key enzyme controlling DNL in human adipose tissue, fatty acid synthase (FAS), is uncertain. Adipose tissue mRNA for FAS is increased in lean and obese subjects when hepatic DNL is elevated by a eucaloric, low-fat, high-sugar diet. Twelve lean and seven obese volunteers were given two eucaloric diets (10% vs. 30% fat; 75% vs. 55% carbohydrate; sugar/starch 60/40) each for 2 weeks by a random-order cross-over design. FAS mRNA in abdominal and gluteal adipose tissues was compared to hepatic DNL measured in serum by isotopic and nonisotopic methods. Adipose tissue mRNA for tumor necrosis factor-alpha and IL-6, which are inflammatory cytokines that modulate DNL, was also assayed. The low-fat high-sugar diet induced a 4-fold increase in maximum hepatic DNL (P<.001) but only a 1.3-fold increase in adipose tissue FAS mRNA (P=.029) and no change in cytokine mRNA. There was a borderline significant positive correlation between changes in FAS mRNA and hepatic DNL (P=.039). Compared to lean subjects, obese subjects had lower levels of FAS mRNA and higher levels of cytokine mRNA (P<.001). The results suggest that key elements of human adipose tissue DNL are less responsive to dietary carbohydrate than is hepatic DNL and may be regulated by diet-independent factors. Irrespective of diet, there is reduced expression of the FAS gene and increased expression of cytokine genes in adipose tissues of obese subjects.

Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots.

PubMed

Long, N M; Rule, D C; Zhu, M J; Nathanielsz, P W; Ford, S P

2012-07-01

Maternal nutrient restriction leads to alteration in fetal adipose tissue, and offspring from obese mothers have an increased risk of developing obesity. We hypothesized that maternal obesity increases fetal adipogenesis. Multiparous ewes (Columbia/Rambouillet cross 3 to 5 yr of age) carrying twins were assigned to a diet of 100% (Control; CON; n = 4) or 150% (Obese; OB, n = 7) of NRC maintenance requirements from 60 d before conception until necropsy on d 135 of gestation. Maternal and fetal plasma were collected and stored at -80°C for glucose and hormone analyses. Fetal measurements were made at necropsy, and perirenal, pericardial, and subcutaneous adipose tissues were collected from 7 male twin fetuses per group and snap frozen at -80°C. Protein and mRNA expression of fatty acid translocase [cluster of differentiation (CD) 36], fatty acid transport proteins (FATP) 1 and 4, insulin-sensitive glucose transporter (GLUT-4), fatty acid synthase (FASN), and acetyl-coA carboxylase (ACC) was evaluated. Fetal weight was similar, but fetal carcass weight (FCW) was reduced (P < 0.05) in OB versus CON fetuses. Pericardial and perirenal adipose tissue weights were increased (P < 0.05) as a percentage of FCW in OB versus CON fetuses, as was subcutaneous fat thickness (P < 0.001). Average adipocyte diameter was greater (P < 0.01) in the perirenal fat and the pericardial fat (P = 0.06) in OB fetuses compared with CON fetuses. Maternal plasma showed no difference (P > 0.05) in glucose or other hormones, fetal plasma glucose was similar (P = 0.42), and cortisol, IGF-1, and thyroxine were reduced (P ≤ 0.05) in OB fetuses compared with CON fetuses. Protein and mRNA expression of CD 36, FATP 1 and 4, and GLUT-4 were increased (P ≤ 0.05) in all fetal adipose depots in OB versus CON fetuses. The mRNA expression of FASN and ACC was increased (P < 0.05) in OB vs. CON fetuses in all 3 fetal adipose tissue depots. Fatty acid concentrations were increased (P = 0.01) in the perirenal depot of OB versus CON fetuses, and specific fatty acid concentrations were altered (P < 0.05) in subcutaneous and pericardial adipose tissue because of maternal obesity. In conclusion, maternal obesity was associated with increased fetal adiposity, increased fatty acid and glucose transporters, and increased expression of enzymes mediating fatty acid biosynthesis in adipose depots. These alterations, if maintained into the postnatal period, could predispose the offspring to later obesity and metabolic disease.

Prenatal Stress due to a Natural Disaster Predicts Adiposity in Childhood: The Iowa Flood Study

PubMed Central

Dancause, Kelsey N.; Laplante, David P.; Hart, Kimberly J.; O'Hara, Michael W.; Brunet, Alain

2015-01-01

Prenatal stress can affect lifelong physical growth, including increased obesity risk. However, human studies remain limited. Natural disasters provide models of independent stressors unrelated to confounding maternal characteristics. We assessed degree of objective hardship and subjective distress in women pregnant during severe flooding. At ages 2.5 and 4 years we assessed body mass index (BMI), subscapular plus triceps skinfolds (SS + TR, an index of total adiposity), and SS : TR ratio (an index of central adiposity) in their children (n = 106). Hierarchical regressions controlled first for several potential confounds. Controlling for these, flood exposure during early gestation predicted greater BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater maternal hardship and distress due to the floods, as well as other nonflood life events during pregnancy, independently predicted greater increase in total adiposity between 2.5 and 4 years. These results support the hypothesis that prenatal stress increases adiposity beginning in childhood and suggest that early gestation is a sensitive period. Results further highlight the additive effects of maternal objective and subjective stress, life events, and depression, emphasizing the importance of continued studies on multiple, detailed measures of maternal mental health and experience in pregnancy and child growth. PMID:25874124

Prenatal stress due to a natural disaster predicts adiposity in childhood: the Iowa Flood Study.

PubMed

Dancause, Kelsey N; Laplante, David P; Hart, Kimberly J; O'Hara, Michael W; Elgbeili, Guillaume; Brunet, Alain; King, Suzanne

2015-01-01

Prenatal stress can affect lifelong physical growth, including increased obesity risk. However, human studies remain limited. Natural disasters provide models of independent stressors unrelated to confounding maternal characteristics. We assessed degree of objective hardship and subjective distress in women pregnant during severe flooding. At ages 2.5 and 4 years we assessed body mass index (BMI), subscapular plus triceps skinfolds (SS + TR, an index of total adiposity), and SS : TR ratio (an index of central adiposity) in their children (n = 106). Hierarchical regressions controlled first for several potential confounds. Controlling for these, flood exposure during early gestation predicted greater BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater maternal hardship and distress due to the floods, as well as other nonflood life events during pregnancy, independently predicted greater increase in total adiposity between 2.5 and 4 years. These results support the hypothesis that prenatal stress increases adiposity beginning in childhood and suggest that early gestation is a sensitive period. Results further highlight the additive effects of maternal objective and subjective stress, life events, and depression, emphasizing the importance of continued studies on multiple, detailed measures of maternal mental health and experience in pregnancy and child growth.

Pomegranate vinegar attenuates adiposity in obese rats through coordinated control of AMPK signaling in the liver and adipose tissue

PubMed Central

2013-01-01

Background The effect of pomegranate vinegar (PV) on adiposity was investigated in high-fat diet (HF)-induced obese rats. Methods The rats were divided into 5 groups and treated with HF with PV or acetic acid (0, 6.5 or 13% w/w) for 16 weeks. Statistical analyses were performed by the Statistical Analysis Systems package, version 9.2. Results Compared to control, PV supplementation increased phosphorylation of AMP-activated protein kinase (AMPK), leading to changes in mRNA expressions: increases for hormone sensitive lipase and mitochondrial uncoupling protein 2 and decreases for sterol regulatory element binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptorγ (PPARγ) in adipose tissue; increases for PPARα and carnitinepalmitoyltransferase-1a (CPT-1a) and decrease for SREBP-1c in the liver. Concomitantly, PV reduced increases of body weight (p = 0.048), fat mass (p = 0.033), hepatic triglycerides (p = 0.005), and plasma triglycerides (p = 0.001). Conclusions These results suggest that PV attenuates adiposity through the coordinated control of AMPK, which leads to promotion of lipolysis in adipose tissue and stimulation of fatty acid oxidation in the liver. PMID:24180378

Study protocol for the FITR Heart Study: Feasibility, safety, adherence, and efficacy of high intensity interval training in a hospital-initiated rehabilitation program for coronary heart disease.

PubMed

Taylor, Jenna; Keating, Shelley E; Leveritt, Michael D; Holland, David J; Gomersall, Sjaan R; Coombes, Jeff S

2017-12-01

For decades, moderate intensity continuous training (MICT) has been the cornerstone of exercise prescription for cardiac rehabilitation (CR). High intensity interval training (HIIT) is now recognized in CR exercise guidelines as an appropriate and efficient modality for improving cardiorespiratory fitness, a strong predictor of mortality. However, the clinical application of HIIT in a real world CR setting, in terms of feasibility, safety, and long-term adherence, needs further investigation to address ongoing reservations. Furthermore, studies using objective measures of exercise intensity (such as heart rate; HR) have produced variable outcomes. Therefore we propose investigating the use of subjective measures (such as rating of perceived exertion (RPE)) for prescribing exercise intensity. One hundred adults with coronary artery disease (CAD) attending a hospital-initiated CR program will be randomized to 1) HIIT: 4 × 4 min high intensity intervals at 15-18 RPE interspersed with 3-min active recovery periods or 2) MICT: usual care exercise including 40 min continuous exercise at a moderate intensity corresponding to 11-13 RPE. Primary outcome is change in exercise capacity (peak VO 2 ) following 4 weeks of exercise training. Secondary outcome measures are: feasibility, safety, exercise adherence, body composition, vascular function, inflammatory markers, intrahepatic lipid, energy intake, and dietary behavior over 12-months; and visceral adipose tissue (VAT) following 12 weeks of exercise training. This study aims to address the ongoing concerns regarding the practicality and safety of HIIT in CR programs. We anticipate study findings will lead to the development of a standardized protocol to facilitate CR programs to incorporate HIIT as a standard exercise option for appropriate patients.

Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

PubMed Central

Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

2015-01-01

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

Male mice are susceptible to high fat diet-induced hyperglycaemia and display increased circulatory retinol binding protein 4 (RBP4) levels and its expression in visceral adipose depots.

PubMed

Asha, G V; Raja Gopal Reddy, M; Mahesh, M; Vajreswari, A; Jeyakumar, S M

2016-01-01

Vitamin A and its metabolites are known to modulate adipose tissue development and its associated complications. Here, we assessed the vitamin A status and its metabolic pathway gene expression in relation to sexual dimorphism by employing 35 days old C57BL/6J male and female mice, which were fed either stock or high fat (HF) diet for 26 weeks. HF diet feeding increased body weight/weight gain and white adipose tissue (WAT) of visceral and subcutaneous regions, however, increase in vitamin A levels observed only in subcutaneous WAT. Further, the expression of most of the vitamin A metabolic pathway genes showed no sexual dimorphism. The observed HF diet-induced hyperglycaemia in male corroborates with increased retinol binding protein 4 (RBP4) levels in plasma and its expression in visceral adipose depots. In conclusion, the male mice are susceptible to high fat diet-induced hyperglycaemia and display higher plasma RBP4 levels, possibly due to its over-expression in visceral adipose depots.

The tumour suppressor CDKN2A/p16INK4a regulates adipogenesis and bone marrow-dependent development of perivascular adipose tissue

PubMed Central

Wouters, Kristiaan; Deleye, Yann; Hannou, Sarah A; Vanhoutte, Jonathan; Maréchal, Xavier; Coisne, Augustin; Tagzirt, Madjid; Derudas, Bruno; Bouchaert, Emmanuel; Duhem, Christian; Vallez, Emmanuelle; Schalkwijk, Casper G; Pattou, François; Montaigne, David; Staels, Bart; Paumelle, Réjane

2017-01-01

The genomic CDKN2A/B locus, encoding p16INK4a among others, is linked to an increased risk for cardiovascular disease and type 2 diabetes. Obesity is a risk factor for both cardiovascular disease and type 2 diabetes. p16INK4a is a cell cycle regulator and tumour suppressor. Whether it plays a role in adipose tissue formation is unknown. p16INK4a knock-down in 3T3/L1 preadipocytes or p16INK4a deficiency in mouse embryonic fibroblasts enhanced adipogenesis, suggesting a role for p16INK4a in adipose tissue formation. p16INK4a-deficient mice developed more epicardial adipose tissue in response to the adipogenic peroxisome proliferator activated receptor gamma agonist rosiglitazone. Additionally, adipose tissue around the aorta from p16INK4a-deficient mice displayed enhanced rosiglitazone-induced gene expression of adipogenic markers and stem cell antigen, a marker of bone marrow-derived precursor cells. Mice transplanted with p16INK4a-deficient bone marrow had more epicardial adipose tissue compared to controls when fed a high-fat diet. In humans, p16INK4a gene expression was enriched in epicardial adipose tissue compared to other adipose tissue depots. Moreover, epicardial adipose tissue from obese humans displayed increased expression of stem cell antigen compared to lean controls, supporting a bone marrow origin of epicardial adipose tissue. These results show that p16INK4a modulates epicardial adipose tissue development, providing a potential mechanistic link between the genetic association of the CDKN2A/B locus and cardiovascular disease risk. PMID:28868898

Adipose tissue as an endocrine organ.

PubMed

McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

2014-02-01

Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of supervised weight loss and intentional weight regain on sex hormone binding globulin and testosterone in premenopausal women.

PubMed

Aubuchon, Mira; Liu, Ying; Petroski, Gregory F; Thomas, Tom R; Polotsky, Alex J

2016-08-01

What is the impact of intentional weight loss and regain on serum androgens in women? We conducted an ancillary analysis of prospectively collected samples from a randomized controlled trial. The trial involved supervised 10% weight loss (8.5 kg on average) with diet and exercise over 4-6 months followed by supervised intentional regain of 50% of the lost weight (4.6 kg on average) over 4-6 months. Participants were randomized prior to the partial weight regain component to either continuation or cessation of endurance exercise. Analytic sample included 30 obese premenopausal women (mean age of 40 ± 5.9 years, mean baseline body mass index (BMI) of 32.9 ± 4.2 kg/m(2)) with metabolic syndrome. We evaluated sex hormone binding globulin (SHBG), total testosterone (T), free androgen index (FAI), and high molecular weight adiponectin (HMWAdp). Insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI), and visceral adipose tissue (VAT) measured in the original trial were reanalyzed for the current analytic sample. Insulin, HOMA, and QUICKI improved with weight loss and were maintained despite weight regain. Log-transformed SHBG significantly increased from baseline to weight loss, and then significantly decreased with weight regain. LogFAI and logVAT decreased similarly and increased with weight loss followed by weight regain. No changes were found in logT and LogHMWAdp. There was no significant difference in any tested parameters by exercise between the groups. SHBG showed prominent sensitivity to body mass fluctuations, as reduction with controlled intentional weight regain showed an inverse relationship to VAT and occurred despite stable HMWAdp and sustained improvements with insulin resistance. FAI showed opposite changes to SHBG, while T did not change significantly with weight. Continued exercise during weight regain did not appear to impact these findings.

Aerobic Exercise and Weight Loss Reduce Vascular Markers of Inflammation and Improve Insulin Sensitivity in Obese Women

PubMed Central

Ryan, Alice S.; Ge, Shealinna; Blumenthal, Jacob B.; Serra, Monica C.; Prior, Steven J.; Goldberg, Andrew P.

2014-01-01

Background/Objectives To examine the relationships of plasma and tissue markers of systemic and vascular inflammation to obesity and insulin resistance and determine the effects of aerobic exercise training+weight loss (AEX+WL) and weight loss (WL) on these biomarkers. Design Prospective controlled study. Participants Seventy-seven overweight and obese sedentary postmenopausal women. Interventions Six months, 3d/wk AEX+WL (n=37) or WL (n=40). Measurements Total body dual-energy x-ray absorptiometry, abdominal computed tomography scans, hyperinsulinemic-euglycemic clamps, adipose tissue biopsies (n=28), and blood for Homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Results Body weight, %fat, visceral fat, triglyceride levels and systolic blood pressure decreased comparably after WL and AEX+WL (P<0.05). VO2max increased 16% after AEX+WL (P<0.001). Insulin resistance decreased in both groups (P<0.01). Glucose utilization increased 10% (P< 0.05) after AEX+WL and 8% with WL (P=0.07). AEX+WL and WL decreased CRP by 29% and 21%, (P<0.05). SAA levels decreased two-fold more after AEX+WL (−19%, P<0.05) than with WL (−9%, P=0.08). Plasma sICAM-1 and sVCAM-1 levels did not change; however, women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose, insulin and insulin resistance (P<0.05). Gluteal ICAM mRNA levels decreased 27% after AEX+WL (P<0.05) and did not change after WL. Conclusion Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP and SAA and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women. PMID:24635342

Physical exercise antagonizes clinical and anatomical features characterizing Lieber-DeCarli diet-induced obesity and related metabolic disorders.

PubMed

Gonçalves, Inês O; Passos, Emanuel; Rocha-Rodrigues, Sílvia; Torrella, Joan R; Rizo, David; Santos-Alves, Estela; Portincasa, Piero; Martins, Maria J; Ascensão, António; Magalhães, José

2015-04-01

Lieber-DeCarli diet has been used to induce obesity and non-alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related information on this diet model exists and being exercise an advised strategy to counteract metabolic diseases, we aimed to analyze the preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect of exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet. In the beginning of the protocol, Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9-weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5 d/wk/60 min/day). At this time, a blood sample was collected for biochemical analysis. At the end of protocol (17-weeks) anatomic measures were assessed. Heart, liver, femur and visceral fat were weighted and blood was collected again. Liver section was used for histopathological examination. At 17-weeks, high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by both exercises. However, ET was the only intervention able to diminished obesity-related measures and the histological features of NASH. Moreover, blood analysis at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL while VLDL and TG levels were decreased (HS vs. SS). Notably, although these parameters were counteracted after 9-weeks of VPA, they were transitory and not observed after 17-weeks. ET used as a therapeutic tool mitigated the clinical/anatomical-related features induced by Liber-DeCarli diet, thus possibly contributing to control obesity and metabolic disorders. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Cross-lagged associations between children's stress and adiposity: the Children's Body Composition and Stress study.

PubMed

Michels, Nathalie; Sioen, Isabelle; Boone, Liesbet; Clays, Els; Vanaelst, Barbara; Huybrechts, Inge; De Henauw, Stefaan

2015-01-01

The public health threats stress and adiposity have previously been associated with each other. Longitudinal studies are needed to reveal whether this association is bidirectional and the moderating factors. In the longitudinal Children's Body Composition and Stress study, 316 children (aged 5-12 years) had measures of stress (questionnaires concerning negative life events, problem behavior, and emotions) and adiposity (body mass index, waist-to-height ratio, and fat percentage) in three waves at 1-year intervals. The bidirectionality of the association between stress and adiposity was examined using cross-lagged analyses. We tested moderation by cortisol and life-style (physical activity, screen time, food consumption, eating behavior and sleep duration). Adiposity (body mass index: β = 0.48 and fat percentage: β = 0.18; p < .001) were associated with subsequent increased stress levels, but stress was not directly related to subsequent increases in adiposity indices. Cortisol and life-style factors displayed a moderating effect on the association between stress and adiposity. Stress was positively associated with adiposity in children with high cortisol awakening patterns (β = 0.204; p = .020) and high sweet food consumption (β = 0.190; p = .031), whereas stress was associated with lower adiposity in the most active children (β = -0.163; p = .022). Stress is associated with the development of children's adiposity, but the effects depend on cortisol levels and life-style factors. This creates new perspectives for multifactorial obesity prevention programs. Our results also highlight the adverse effect of an unhealthy body composition on children's psychological well-being.

Maternal high-fat diet modulates brown adipose tissue response to B-adrenergic agonist

USDA-ARS?s Scientific Manuscript database

Maternal obesity increases offspring risk for several metabolic diseases. We previously showed that offspring of obese dams are predisposed to obesity, liver and adipose tissue anomalies. However, the effect of maternal obesity on developmental programing brown adipose tissue (BAT) is poorly underst...

Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

PubMed

Jansen, H J; Stienstra, R; van Diepen, J A; Hijmans, A; van der Laak, J A; Vervoort, G M M; Tack, C J

2013-12-01

Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. ClinicalTrials.gov: NCT00781495. The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.

The role of Ad-36 as a risk factor in males with gynecomastia.

PubMed

Kocazeybek, Bekir; Saribas, Suat; Ergin, Sevgi

2015-12-01

Gynecomastia is highly prevalent worldwide and Adenovirus-36 (Ad-36), recently implicated in increased adipose tissue deposition due to its affinity for adipose tissue, is a potential etiological agent in the development of obesity and therefore we hypothesized that Ad-36 may also play a role in the development of gynecomastia by possibly accompanying increased regional adiposity. To support our hypothesis, we conducted a study that included 33 adult males with gynecomastia (PG) and 15 adult males as the patient control group (HCG). Leptin and adiponectin levels were monitored using ELISA. A significant difference in Ad-36 antibody positivity was found between the groups (p<0.05). Average leptin levels were found to be higher, but average adiponectin levels were found to be lower in Ad-36 Ab(+) patient group. No Ad-36 DNA was detected in any tissue samples. In conclusion, we hypothesize that low-grade chronic inflammation, which was caused by Ad-36 infection, possibly caused an increase in circulating leptin. This in turn may have caused an increase in local or circulating estrogens and/or the estrogen/androgen ratio by stimulating the aromatase enzyme activity in adipose stromal cells and breast tissues. We suggest that gynecomastia may develop following an increase in aromatase enzyme activity, by which more oestrogen is produced and the estrogen-androgen balance disrupted. Also, regional adipose tissue enlargements may cause the excessive production of estrogens leading to gynecomastia. Adipose tissue has been recognized as a major endocrine organ in recent years. Another plausible explanation is excessive aromatization of androgens to estrogens by peripheral adipose tissue may promote gynecomastia in males. Moreover, our results suggest that there might be a relationship between Ad-36 and gynecomastia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cbl downregulation increases RBP4 expression in adipocytes of female mice

PubMed Central

Ameen, Gulizar Issa

2018-01-01

Obesity leads to adipose tissue dysfunction, insulin resistance and diabetes. Adipose tissue produces adipokines that contribute to regulate insulin sensitivity. In turn, insulin stimulates the production and release of some adipokines. Casitas-b-lymphoma proteins (c-Cbl, Cbl-b and Cbl3) are intracellular adaptor signalling proteins that are rapidly phosphorylated by activation of tyrosine kinase receptors. c-Cbl is rapidly phosphorylated by insulin in adipocytes. Here, we tested the hypothesis that Cbl signalling regulates adipokine expression in adipose tissue. We determined the adipokine profile of WAT of Cbl−/− and Cbl+/+ mice in the C57BL6 background. Female Cbl−/− mice exhibited altered expression of adiponectin, leptin and RBP4 in visceral adipose tissue, while no significant changes were seen in male mice. TNFα and IL6 levels were unaffected by Cbl depletion. RBP4 expression was unchanged in liver. Adipose tissue of Cbl−/− animals showed increased basal activation of extracellular regulated kinases (ERK1/2) compared to Cbl+/+. c-Cbl knockdown in 3T3L1 adipocytes also increased basal ERK phosphorylation and RBP4 expression. Inhibition of ERK1/2 phosphorylation in Cbl-depleted 3T3L1 adipocytes or in adipose tissue explants of Cbl−/− mice reduced RBP4 mRNA. 17β-Estradiol increased RBP4 mRNA in adipocytes. Cbl depletion did not change ER expression but increased phosphorylation of ERα at S118, a target site for ERK1/2. ERK1/2 inhibition reduced phosphoER and RBP4 levels. These findings suggest that Cbl contributes to regulate RBP4 expression in adipose of female mice through ERK1/2-mediated activation of ERα. Since Cbl signalling is compromised in diabetes, these data highlight a novel mechanism that upregulates RBP4 locally. PMID:29114012

Genetics and blood pressure response to exercise, and its interactions with adiposity.

PubMed

Rankinen, T; Bouchard, C

2002-01-01

Regular aerobic exercise has the potential to induce several beneficial health effects, including a decrease in blood pressure level, especially in hypertensive patients and in subjects with high-normal blood pressure. However, it is also well documented that some people show more pronounced blood pressure responses to endurance training than others, despite identical training programs and similar initial blood pressure levels. This kind of variation is an example of normal biologic diversity and most likely originates from interactions with genetic factors. Data from genetic epidemiologic studies indicate that there is a genetic component that affects both resting blood pressure and blood pressure responses to acute exercise. Evidence from molecular genetic studies is scarce, but the first reports suggest that DNA sequence variation in the hypertension candidate genes, such as angiotensinogen, also modify blood pressure responses to endurance training. The current knowledge regarding the role of genetic factors in the modification of blood pressure responses to endurance training will be summarized and discussed. Copyright 2002 CHF, Inc.

Implication of Low Level Inflammation in the Insulin Resistance of Adipose Tissue at Late Pregnancy

PubMed Central

de Castro, J.; Sevillano, J.; Marciniak, J.; Rodriguez, R.; González-Martín, C.; Viana, M.; Eun-suk, O. H.; de Mouzon, S. Hauguel; Herrera, E.

2011-01-01

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance. PMID:21914778

Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men.

PubMed Central

Fried, S K; Russell, C D; Grauso, N L; Brolin, R E

1993-01-01

There are marked variations in the activity of lipoprotein lipase (LPL) among adipose depots, particularly in women. Consistent with data on LPL activity, the level of expression of LPL mRNA was lower in omental (OM) than subcutaneous (SQ) adipose tissue of women. To investigate the cellular basis of these differences, OM and SQ adipose tissues obtained at surgery from obese men and women were placed in organ culture for 7 d with varying concentrations of insulin and dexamethasone. Insulin increased levels of LPL mRNA and LPL activity in abdominal SQ but not OM adipose tissue. Dexamethasone also increased LPL mRNA and LPL activity, and these effects were more marked in the OM adipose tissue, particularly in men. When insulin and dexamethasone were added together, synergistic increases in LPL activity were seen in both depots, and this was in part explained at the level of LPL mRNA. The SQ depot was more sensitive to the effects of submaximal doses of dexamethasone in the presence of insulin. The maximum activity of LPL induced by insulin or insulin plus dexamethasone was higher in the SQ than in the OM depot of women, and this was associated with higher levels of LPL mRNA. Rates of LPL synthesis paralleled LPL mRNA levels. These data show that insulin and glucocorticoids influence human adipose tissue LPL activity at the level of LPL gene expression, as well as posttranslationally, and that responsiveness to these hormonal effects is dependent on adipose depot and gender. Images PMID:8227334

Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance

PubMed Central

Palanivel, R.; Fullerton, M. D.; Galic, S.; Honeyman, J.; Hewitt, K. A.; Jorgensen, S. B.; Steinberg, G. R.

2017-01-01

Aims/hypothesis Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known. Methods We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed. Results The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic–euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1). Conclusions/interpretation These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity. PMID:22872213

Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

PubMed

Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

2010-04-09

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

Predictors of endothelial function in employees with sedentary occupations in a worksite exercise program.

PubMed

Lippincott, Margaret F; Desai, Aditi; Zalos, Gloria; Carlow, Andrea; De Jesus, Janet; Blum, Arnon; Smith, Kevin; Rodrigo, Maria; Patibandla, Sushmitha; Chaudhry, Hira; Glaser, Alexander P; Schenke, William H; Csako, Gyorgy; Waclawiw, Myron A; Cannon, Richard O

2008-10-01

A sedentary workforce may be at increased risk for future cardiovascular disease. Exercise at the work site has been advocated, but effects on endothelium as a biomarker of risk and relation to weight loss, lipid changes, or circulating endothelial progenitor cells (EPCs) have not been reported. Seventy-two office and laboratory employees (58 women; average age 45 years, range 22 to 62; 26 with body mass index values >30 kg/m(2)) completed 3 months of participation in the National Heart, Lung, and Blood Institute's Keep the Beat program, with the determination of vital signs, laboratory data, and peak oxygen consumption (VO(2)) during treadmill exercise. Brachial artery endothelium was tested by flow-mediated dilation (FMD), which at baseline was inversely associated with Framingham risk score (r = -0.3689, p <0.0001). EPCs were quantified by colony assay. With exercise averaging 98 +/- 47 minutes each workweek, there was improvement in FMD (from 7.8 +/- 3.4% to 8.5 +/- 3.0%, p = 0.0096) and peak VO(2) (+1.2 +/- 3.1 ml O(2)/kg/min, p = 0.0028), with reductions in diastolic blood pressure (-2 +/- 8 mm Hg, p = 0.0478), total cholesterol (-8 +/- 25 mg/dl, p = 0.0131), and low-density lipoprotein cholesterol (-7 +/- 19 mg/dl, p = 0.0044) but with a marginal reduction in weight (-0.5 +/- 2.1 kg, p = 0.0565). By multiple regression modeling, lower baseline FMD, greater age, reductions in total and low-density lipoprotein cholesterol and diastolic blood pressure, and increases in EPC colonies and peak VO(2) were jointly statistically significant predictors of change in FMD and accounted for 47% of the variability in FMD improvement with program participation. Results were similar when modeling was performed for women only. In contrast, neither adiposity at baseline nor change in weight was a predictor of improved endothelial function. In conclusion, daily exercise achievable at their work sites by employees with sedentary occupations improves endothelial function, even with the absence of weight loss, which may decrease cardiovascular risk, if sustained.

Defining the Adipose Tissue Proteome of Dairy Cows to Reveal Biomarkers Related to Peripartum Insulin Resistance and Metabolic Status.

PubMed

Zachut, Maya

2015-07-02

Adipose tissue is a central regulator of metabolism in dairy cows; however, little is known about the association between various proteins in adipose tissue and the metabolic status of peripartum cows. Therefore, the objectives were to (1) examine total protein expression in adipose tissue of dairy cows and (2) identify biomarkers in adipose that are linked to insulin resistance and to cows' metabolic status. Adipose tissue biopsies were obtained from eight multiparous cows at -17 and +4 days relative to parturition. Proteins were analyzed by intensity-based, label-free, quantitative shotgun proteomics (nanoLC-MS/MS). Cows were divided into groups with insulin-resistant (IR) and insulin-sensitive (IS) adipose according to protein kinase B phosphorylation following insulin stimulation. Cows with IR adipose lost more body weight postpartum compared with IS cows. Differential expression of 143 out of 586 proteins was detected in prepartum versus postpartum adipose. Comparing IR to IS adipose revealed differential expression of 18.9% of the proteins; those related to lipolysis (hormone-sensitive lipase, perilipin, monoglycerol lipase) were increased in IR adipose. In conclusion, we found novel biomarkers related to IR in adipose and to metabolic status that could be used to characterize high-yielding dairy cows that are better adapted to peripartum metabolic stress.

Adiposity in Children and CVD Risk: ApoB48 Has a Stronger Association With Central Fat Than Classic Lipid Markers.

PubMed

Wilke, Michaelann S; Maximova, Katerina; Henderson, Mélanie; Levy, Emile; Paradis, Gilles; O'Loughlin, Jennifer; Tremblay, Angelo; Proctor, Spencer D

2016-07-01

Atherosclerotic vascular disease begins in childhood and while progression is multifactorial, obesity in early life is an important risk factor for its development. To determine whether fasting apoB48 remnant lipoproteins (relative to classic lipid markers), is elevated with increasing central adiposity over time in a cohort of Canadian children with a family history of obesity. Data were drawn from the ongoing prospective cohort of 630 Caucasian families in Québec, Canada, recruited to assess determinants and effects of childhood obesity (Québec Adiposity and Lifestyle Investigation in Youth [QUALITY]cohort). Children who attended baseline and first followup clinic visits (n =570; age 9.6 y). Trunk fat mass was determined by dual energy x-ray absorptiometry. Central fat mass index was calculated as CFMI = trunk fat mass/height(2) (kg/m(2)) and groups created (CFMI <1.5; 1.5-3.0; ≥3.0 kg/m(2)) to suggest lower, moderate, or higher central adiposity. Changes over time in outcomes (apoB48, triglyceride and total, low-, and high-density lipoprotein cholesterol) were compared using paired t test and multiple regression that adjusted for age, sex, and Tanner stage. Classic lipid markers (total and low-density lipoprotein cholesterol) improved at followup, whereas apoB48 became worse (increased). ApoB48 increased with increasing central adiposity, highest (37%) in children who transitioned from lower- to moderate-CFMI groups (ΔapoB48 = 1.5 μg/mL). For every 1 kg/m(2) increase in central adiposity over the 2-y period, an increase in apoB48 was 14-fold greater among children with lower baseline CFMI, compared with higher CFMI. Increased fasting concentrations of apoB48 may be representative of changes in adiposity at lower levels of central fat (early periods of risk).

Broiler chicken adipose tissue dynamics during the first two weeks post-hatch.

PubMed

Bai, Shiping; Wang, Guoqing; Zhang, Wei; Zhang, Shuai; Rice, Brittany Breon; Cline, Mark Andrew; Gilbert, Elizabeth Ruth

2015-11-01

Selection of broiler chickens for growth has led to increased adipose tissue accretion. To investigate the post-hatch development of adipose tissue, the abdominal, clavicular, and subcutaneous adipose tissue depots were collected from broiler chicks at 4 and 14 days post-hatch. As a percent of body weight, abdominal fat increased (P<0.001) with age. At day 4, clavicular and subcutaneous fat depots were heavier (P<0.003) than abdominal fat whereas at day 14, abdominal and clavicular weighed more (P<0.003) than subcutaneous fat. Adipocyte area and diameter were greater in clavicular and subcutaneous than abdominal fat at 4 and 14 days post-hatch (P<0.001). Glycerol-3-phosphate dehydrogenase (G3PDH) activity increased (P<0.001) in all depots from day 4 to 14, and at both ages was greatest in subcutaneous, intermediate in clavicular, and lowest in abdominal fat (P<0.05). In clavicular fat, peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein (CEBP)α, CEBPβ, fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL), neuropeptide Y (NPY), and NPY receptor 5 (NPYR5) mRNA increased and NPYR2 mRNA decreased from day 4 to 14 (P<0.001). Thus, there are site-specific differences in broiler chick adipose development, with larger adipocytes and greater G3PDH activity in subcutaneous fat at day 4, more rapid growth of abdominal fat, and clavicular fat intermediate for most traits. Adipose tissue expansion was accompanied by changes in gene expression of adipose-associated factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of adipose tissue-derived stem cells in the progression of renal disease.

PubMed

Donizetti-Oliveira, Cassiano; Semedo, Patricia; Burgos-Silva, Marina; Cenedeze, Marco Antonio; Malheiros, Denise Maria Avancini Costa; Reis, Marlene Antônia Dos; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2011-03-01

To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats.

PubMed

Sen, Sarbattama; Simmons, Rebecca A

2010-12-01

Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

TRB3 gene silencing activates AMPK in adipose tissue with beneficial metabolic effects in obese and diabetic rats.

PubMed

Sun, Xiaoyan; Song, Ming; Wang, Hui; Zhou, Huimin; Wang, Feng; Li, Ya; Zhang, Yun; Zhang, Wei; Zhong, Ming; Ti, Yun

2017-06-17

Our previous study had suggested Tribbles homolog 3 (TRB3) might be involved in metabolic syndrome via adipose tissue. Given prior studies, we sought to determine whether TRB3 plays a major role in adipocytes and adipose tissue with beneficial metabolic effects in obese and diabetic rats. Fully differentiated 3T3-L1 adipocytes were incubated to induce insulin resistant adipocytes. Forty male Sprague-Dawley rats were all fed high-fat (HF) diet. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (STZ). Compared with control group, in insulin resistant adipocytes, protein levels of insulin receptor substrate-1(IRS-1), glucose transporter 4(GLUT4) and phosphorylated-AMP-activated protein kinase (p-AMPK)were reduced, TRB3 protein level and triglyceride level were significantly increased, glucose uptake was markedly decreased. TRB3 silencing alleviated adipocytes insulin resistance. With TRB3 gene silencing, protein levels of IRS-1, GLUT4 and p-AMPK were significantly increased in adipocytes. TRB3 gene silencing decreased blood glucose, ameliorated insulin sensitivity and adipose tissue remodeling in diabetic rats. TRB3 silencing decreased triglyceride, increased glycogen simultaneously in diabetic epididymal and brown adipose tissues (BAT). Consistently, p-AMPK levels were increased in diabetic epididymal adipose tissue, and BAT after TRB3-siRNA treatment. TRB3silencing increased phosphorylation of Akt in liver, and improved liver insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Chronic glucocorticoid exposure-induced epididymal adiposity is associated with mitochondrial dysfunction in white adipose tissue of male C57BL/6J mice.

PubMed

Yu, Jie; Yu, Bing; He, Jun; Zheng, Ping; Mao, Xiangbing; Han, Guoquan; Chen, Daiwen

2014-01-01

Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue.

Physiological changes in women during exercise in cold environments

NASA Astrophysics Data System (ADS)

Murray, S. J.; Shephard, R. J.; Radomski, M. W. M.

1986-12-01

Both the stress of exercise and the stress of a cold environment have been shown to increase the mobilization and utilization of body fat, thereby reducing body fat stores. Much of the research has been done on either rats or male human subjects. The purpose of this research was to show the physiological changes which occur to young, relatively obese, women who exercised during five consecutive days, for 200 min per day, in each of three environmental, chamber conditions: (1) warm-warm (WW), +15‡C; (2) cold-cold (CC), -20‡C; and (3) cold-warm (CW), -20‡C ambient temperature, with +18‡C air pumped to face masks for warmed air breathing. Oxygen cost of exercise, respiratory quotients, energy intake and utilization, and body composition changes were measured before, during, and after each environmental condition. While the respiratory quotients and the skinfold measurements decreased in the colder conditions, the underwater weighing determined percentage body fat did not show the same decrement as the skinfold measures, indicating a possible translocation of body fat from the subcutaneous depots to the deep body fat depots. Body mass loss was significant (P<0.05) only in the WW condition. Thermogenesis would have been centred in the skeletal muscle and liver during the CW condition; however, with facial and upper airway cooling in the CC condition; brown adipose tissue (BAT) hypertrophy may be postulated at this more intense level of cold stress. Due to a greater stability of depot fat in the female, a longer cold exposure would be required to observe the fully developed BAT thermogenesis which would follow after the consequences of fat translocation which we have documented.

Effect of aerobic interval training on serum IL-10, TNFα, and adipokines levels in women with multiple sclerosis: possible relations with fatigue and quality of life.

PubMed

Mokhtarzade, Motahare; Ranjbar, Rouholah; Majdinasab, Nastaran; Patel, Darpan; Molanouri Shamsi, Mehdieh

2017-08-01

Multiple sclerosis is associated with immune system dysfunction and chronic inflammation; however, possible relations between immunologic and metabolic factors and some psychological indexes such as fatigue and quality of life, especially in relation to exercise training, have not yet been investigated. The present study was designed to investigate the effect of aerobic interval training on interleukin-10/tumor necrosis factor ratio and adipokine (leptin and adiponectin) concentrations in women with multiple sclerosis. Furthermore, the relationship between these factors with fatigue and quality of life were assessed. Forty women with multiple sclerosis (Expanded Disability Status Scale ≤3) were randomized into either a non-exercising control or training group. The training group performed 8-weeks of upper and lower limb aerobic interval training. Serum concentrations of tumor necrosis factorα, interleukin-10, leptin, and adiponectin were measured before and after the 8-week intervention. Moreover, antropometric measures and measures for fatigue and quality of life were determined at the onset of and after exercise training. The results revealed that leptin and tumor necrosis factorα levels significantly decreased subsequent to the aerobic interval training. Although blood adiponectin levels considerably increased in the training group, interleukin-10 and interleukin-10/tumor necrosis factorα ratio underwent no substantial change after the exercise training. In addition, the aerobic interval training was associated with improvement in fatigue, quality of life, and maximal oxygen consumption. Our findings suggested that aerobic interval training can be an effective strategy for managing the immune system at least by its significant impact on inflammatory cytokines and adipokines levels in women with multiple sclerosis. Additionally, this positive impact improved fatigue and adipose tissue indicators.

The role of moderate-to-vigorous physical activity in mediating the relationship between central adiposity and immunometabolic profile in postmenopausal women.

PubMed

Diniz, Tiego A; Rossi, Fabricio E; Silveira, Loreana S; Neves, Lucas Melo; Fortaleza, Ana Claudia de Souza; Christofaro, Diego G D; Lira, Fabio S; Freitas-Junior, Ismael F

2017-01-01

To analyze the role of moderate-to-vigorous physical activity (MVPA) in mediating the relationship between central adiposity and immune and metabolic profile in postmenopausal women. Cross-sectional study comprising 49 postmenopausal women (aged 59.26 ± 8.32 years) without regular physical exercise practice. Body composition was measured by dual-energy X-ray absorptiometry. Fasting blood samples were collected for assessment of nonesterified fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, insulin and estimation of insulin resistance (HOMA-IR). Physical activity level was assessed with an accelerometer (Actigraph GTX3x) and reported as a percentage of time spent in sedentary behavior and MVPA. All analyses were performed using the software SPSS 17.0, with a significance level set at 5%. Sedentary women had a positive relationship between trunk fat and IL-6 (rho = 0.471; p = 0.020), and trunk fat and HOMA-IR (rho = 0.418; p = 0.042). Adiponectin and fat mass (%) were only positively correlated in physically active women (rho = 0.441; p = 0.027). Physically active women with normal trunk fat values presented a 14.7% lower chance of having increased HOMA-IR levels (β [95%CI] = 0.147 [0.027; 0.811]). The practice of sufficient levels of MVPA was a protective factor against immunometabolic disorders in postmenopausal women.

Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

PubMed Central

Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

2016-01-01

The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

Effects of supervised aerobic training on the levels of anti-Mullerian hormone and adiposity measures in women with normo-ovulatory and polycystic ovary syndrome.

PubMed

Al-Eisa, Einas; Gabr, Sami Ali; Alghadir, Ahmad Hieder

2017-04-01

To evaluate the change in the levels of anti-Mullerian hormone, adiponectin, weight loss and fertility parameters in obese women with or without polycystic ovary syndrome, following 12 weeks of supervised aerobic exercise. This study was conducted from August 2013 to October 2014 among obese women with or without polycystic ovary syndrome referred to Obstetrics and Gynecology clinic, Mansoura University Hospital, Faculty of Medicine, Mansoura, Egypt. Patients were classified into three age-matched groups; group A had controls, group B had patients with polycystic ovary syndrome and group C had obese women. Anti-Mullerian hormone, adiponectin, follicle-stimulating hormone, oestrogen, fasting insulin, fasting glucose, homeostasis model of assessment of insulin resistance, antral follicle count, hirsutism score, weight, menstrual cyclicity and ovulatory function were assessed at baseline and following 12 weeks of supervised aerobic exercise. Statistical analysis was performed using SPSS 17. Of the 90 patients, there were 30(33.3%) in each group. The mean age was 28.7±3.84 years in group A, 27.9±4.1 years in group B and 27.6±5.7 in group C. The 30(33.3%) participants who responded to aerobic exercise interventions showed significant improvements in reproductive function), with lower baseline anti-Mullerian hormone levels, greater weight loss and higher adiponectin level compared to the the 30(33.3%) participants who did not respond to the exercise programme. Weight loss, fertility hormones, follicle-stimulating hormone, prolactin, oestrogen, antral follicle count, baseline anti-Mullerian hormone, and adiponectin were significantly correlated to the improvement in reproductive function (p<0.05 each). The change in anti-Mullerian hormone and adiponectin levels correlated significantly with physical activity level in both responders and non-responders (p<0.05). In women with anovulatory syndromes, there were significant improvements in ovarian process with an ovulation rate of 13(43.3%) and a restoration of menstrual cycle with a rate of 17(56.7 %) following 12 weeks of supervised aerobic exercise. Moderate aerobic training for 12 weeks had a positive significant effect on reproductive functions via modulating adiposity, the levels of adiponectin, anti-Mullerian hormone and fertility hormones.

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.

PubMed

Lu, Yingchang; Day, Felix R; Gustafsson, Stefan; Buchkovich, Martin L; Na, Jianbo; Bataille, Veronique; Cousminer, Diana L; Dastani, Zari; Drong, Alexander W; Esko, Tõnu; Evans, David M; Falchi, Mario; Feitosa, Mary F; Ferreira, Teresa; Hedman, Åsa K; Haring, Robin; Hysi, Pirro G; Iles, Mark M; Justice, Anne E; Kanoni, Stavroula; Lagou, Vasiliki; Li, Rui; Li, Xin; Locke, Adam; Lu, Chen; Mägi, Reedik; Perry, John R B; Pers, Tune H; Qi, Qibin; Sanna, Marianna; Schmidt, Ellen M; Scott, William R; Shungin, Dmitry; Teumer, Alexander; Vinkhuyzen, Anna A E; Walker, Ryan W; Westra, Harm-Jan; Zhang, Mingfeng; Zhang, Weihua; Zhao, Jing Hua; Zhu, Zhihong; Afzal, Uzma; Ahluwalia, Tarunveer Singh; Bakker, Stephan J L; Bellis, Claire; Bonnefond, Amélie; Borodulin, Katja; Buchman, Aron S; Cederholm, Tommy; Choh, Audrey C; Choi, Hyung Jin; Curran, Joanne E; de Groot, Lisette C P G M; De Jager, Philip L; Dhonukshe-Rutten, Rosalie A M; Enneman, Anke W; Eury, Elodie; Evans, Daniel S; Forsen, Tom; Friedrich, Nele; Fumeron, Frédéric; Garcia, Melissa E; Gärtner, Simone; Han, Bok-Ghee; Havulinna, Aki S; Hayward, Caroline; Hernandez, Dena; Hillege, Hans; Ittermann, Till; Kent, Jack W; Kolcic, Ivana; Laatikainen, Tiina; Lahti, Jari; Mateo Leach, Irene; Lee, Christine G; Lee, Jong-Young; Liu, Tian; Liu, Youfang; Lobbens, Stéphane; Loh, Marie; Lyytikäinen, Leo-Pekka; Medina-Gomez, Carolina; Michaëlsson, Karl; Nalls, Mike A; Nielson, Carrie M; Oozageer, Laticia; Pascoe, Laura; Paternoster, Lavinia; Polašek, Ozren; Ripatti, Samuli; Sarzynski, Mark A; Shin, Chan Soo; Narančić, Nina Smolej; Spira, Dominik; Srikanth, Priya; Steinhagen-Thiessen, Elisabeth; Sung, Yun Ju; Swart, Karin M A; Taittonen, Leena; Tanaka, Toshiko; Tikkanen, Emmi; van der Velde, Nathalie; van Schoor, Natasja M; Verweij, Niek; Wright, Alan F; Yu, Lei; Zmuda, Joseph M; Eklund, Niina; Forrester, Terrence; Grarup, Niels; Jackson, Anne U; Kristiansson, Kati; Kuulasmaa, Teemu; Kuusisto, Johanna; Lichtner, Peter; Luan, Jian'an; Mahajan, Anubha; Männistö, Satu; Palmer, Cameron D; Ried, Janina S; Scott, Robert A; Stancáková, Alena; Wagner, Peter J; Demirkan, Ayse; Döring, Angela; Gudnason, Vilmundur; Kiel, Douglas P; Kühnel, Brigitte; Mangino, Massimo; Mcknight, Barbara; Menni, Cristina; O'Connell, Jeffrey R; Oostra, Ben A; Shuldiner, Alan R; Song, Kijoung; Vandenput, Liesbeth; van Duijn, Cornelia M; Vollenweider, Peter; White, Charles C; Boehnke, Michael; Boettcher, Yvonne; Cooper, Richard S; Forouhi, Nita G; Gieger, Christian; Grallert, Harald; Hingorani, Aroon; Jørgensen, Torben; Jousilahti, Pekka; Kivimaki, Mika; Kumari, Meena; Laakso, Markku; Langenberg, Claudia; Linneberg, Allan; Luke, Amy; Mckenzie, Colin A; Palotie, Aarno; Pedersen, Oluf; Peters, Annette; Strauch, Konstantin; Tayo, Bamidele O; Wareham, Nicholas J; Bennett, David A; Bertram, Lars; Blangero, John; Blüher, Matthias; Bouchard, Claude; Campbell, Harry; Cho, Nam H; Cummings, Steven R; Czerwinski, Stefan A; Demuth, Ilja; Eckardt, Rahel; Eriksson, Johan G; Ferrucci, Luigi; Franco, Oscar H; Froguel, Philippe; Gansevoort, Ron T; Hansen, Torben; Harris, Tamara B; Hastie, Nicholas; Heliövaara, Markku; Hofman, Albert; Jordan, Joanne M; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Knekt, Paul B; Koskinen, Seppo; Kovacs, Peter; Lehtimäki, Terho; Lind, Lars; Liu, Yongmei; Orwoll, Eric S; Osmond, Clive; Perola, Markus; Pérusse, Louis; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Rivadeneira, Fernando; Rudan, Igor; Salomaa, Veikko; Sørensen, Thorkild I A; Stumvoll, Michael; Tönjes, Anke; Towne, Bradford; Tranah, Gregory J; Tremblay, Angelo; Uitterlinden, André G; van der Harst, Pim; Vartiainen, Erkki; Viikari, Jorma S; Vitart, Veronique; Vohl, Marie-Claude; Völzke, Henry; Walker, Mark; Wallaschofski, Henri; Wild, Sarah; Wilson, James F; Yengo, Loïc; Bishop, D Timothy; Borecki, Ingrid B; Chambers, John C; Cupples, L Adrienne; Dehghan, Abbas; Deloukas, Panos; Fatemifar, Ghazaleh; Fox, Caroline; Furey, Terrence S; Franke, Lude; Han, Jiali; Hunter, David J; Karjalainen, Juha; Karpe, Fredrik; Kaplan, Robert C; Kooner, Jaspal S; McCarthy, Mark I; Murabito, Joanne M; Morris, Andrew P; Bishop, Julia A N; North, Kari E; Ohlsson, Claes; Ong, Ken K; Prokopenko, Inga; Richards, J Brent; Schadt, Eric E; Spector, Tim D; Widén, Elisabeth; Willer, Cristen J; Yang, Jian; Ingelsson, Erik; Mohlke, Karen L; Hirschhorn, Joel N; Pospisilik, John Andrew; Zillikens, M Carola; Lindgren, Cecilia; Kilpeläinen, Tuomas Oskari; Loos, Ruth J F

2016-02-01

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Role of training and detraining on inflammatory and metabolic profile in infarcted rats: influences of cardiovascular autonomic nervous system.

PubMed

Rodrigues, Bruno; Santana, Aline Alves; Santamarina, Aline Boveto; Oyama, Lila Missae; Caperuto, Érico Chagas; de Souza, Cláudio Teodoro; Barboza, Catarina de Andrade; Rocha, Leandro Yanase; Figueroa, Diego; Mostarda, Cristiano; Irigoyen, Maria Cláudia; Lira, Fábio Santos

2014-01-01

The aim of this study was to evaluate the effects of exercise training (ET, 50-70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic profile after myocardial infarction (MI) in rats. Male Wistar rats were divided into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI, n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1 month of DT). After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis), and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI.

Role of Training and Detraining on Inflammatory and Metabolic Profile in Infarcted Rats: Influences of Cardiovascular Autonomic Nervous System

PubMed Central

Santana, Aline Alves; Santamarina, Aline Boveto; Oyama, Lila Missae; Caperuto, Érico Chagas; de Souza, Cláudio Teodoro; Barboza, Catarina de Andrade; Rocha, Leandro Yanase; Figueroa, Diego; Mostarda, Cristiano; Irigoyen, Maria Cláudia; Lira, Fábio Santos

2014-01-01

The aim of this study was to evaluate the effects of exercise training (ET, 50–70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic profile after myocardial infarction (MI) in rats. Male Wistar rats were divided into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI, n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1 month of DT). After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis), and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI. PMID:25045207

Fitness and adiposity as predictors of functional limitation in adults.

PubMed

Maslow, Andréa L; Price, Anna E; Sui, Xuemei; Lee, Duck-chul; Vuori, Ikka; Blair, Steven N

2011-01-01

This study examined the associations of body mass index (BMI), waist circumference (WC), and cardiorespiratory fitness (CRF) with incident functional limitation (IFL) in adults. Patients (n = 2400), 30+ years [mean age, 45.2 (SD, 8.3); 12% women], completed a baseline health examination during 1979 to 1995. CRF was quantified by age-and sex-specific thirds for maximal treadmill exercise test duration. Adiposity was assessed by BMI and WC (grouped for analysis according to clinical guidelines). Incident IFL was identified from mail-back surveys during 1995, 1999, and 2004. After adjusting for potential confounders and either BMI or WC, CRF was inversely related to IFL (P trend < .001). The association between BMI and IFL was significant after adjusting for all confounders (P trend = .002), but not after additional adjustment for CRF (P trend = .23). After controlling for all confounders and CRF, high WC was associated with greater odds of IFL in those aged 30 to 49; normal WC was associated with greater odds of IFL in those aged 50+. CRF was a significant predictor of IFL in middle aged and older adults, independent of overall or abdominal adiposity. Clinicians should consider the importance of preserving functional capacity by recommending regular physical activity for normal-weight and overweight individuals. ©2011 Human Kinetics, Inc.

[Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha].

PubMed

Landeros-Olvera, Erick; López-Alvarenga, Juan Carlos; Nava-González, Edna J; Gallegos-Cabriales, Esther; Lavalle-González, Fernando; Bastarrachea, Raúl A; Salazar González, Bertha Cecilia

2014-01-01

The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n=17, controls n=17) with a body mass index>27kg/m(2). Molecular analysis was performed by immune-fluorescence. Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2μ/ml (P=.008); leptin 20.0 vs. 28.0μ/L (P=.02); and tumour necrosis factor-alpha 4.7 vs. 5.1pg/ml (P=.05). The established exercise (5 sessions a week of exercise of 40min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation

PubMed Central

Evans, Mark; Cogan, Karl E.

2016-01-01

Abstract Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β‐hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post‐exercise recovery period, and the ability to utilise ketone bodies is higher in exercise‐trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti‐lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes. PMID:27861911

The influence of a home-based exercise intervention on human health indices in individuals with chronic spinal cord injury (HOMEX-SCI): study protocol for a randomised controlled trial.

PubMed

Nightingale, Tom E; Walhin, Jean-Philippe; Turner, James E; Thompson, Dylan; Bilzon, James L J

2016-06-08

Spinal cord injury (SCI) creates a complex pathology that can lead to an increase in sedentary behaviours and deleterious changes in body composition. Consequently, individuals with SCI are at increased risk of developing cardiovascular disease and type-2 diabetes mellitus. While the role of physical activity on the reduction of chronic disease risk is well documented in non-disabled individuals the evidence is less conclusive for persons with SCI. The aim of this methodological paper is to outline the design of a study that will assess the role of a home-based exercise intervention on biomarkers of metabolic and cardiovascular health in persons with SCI: the HOMEX-SCI study. Eligible participants will be inactive (physical activity level ≤1.60) individuals, with a chronic (more than 1 year) spinal cord lesion between the second thoracic and the fifth lumbar vertebrae, and aged between 18 and 65 years. Following baseline laboratory testing and lifestyle monitoring, participants will be randomly allocated to a control (CON) group or a 6-week home-based exercise intervention (INT) group. The INT consists of 45 minutes of moderate-intensity (60-65 % peak oxygen uptake) arm-crank exercise four times per week. Participants assigned to the CON group will be asked to maintain their normal lifestyle. The main outcomes of this study (biomarkers of metabolic and cardiovascular health) are obtained from venous blood samples, collected in the fasted and postprandial state. Eight other measurement categories will be assessed: (1) body composition, (2) physical activity, (3) energy intake, (4) measures of health and wellbeing, (5) resting metabolic rate, heart rate and blood pressure, (6) aerobic capacity, (7) immune function, and (8) adipose tissue gene expression. This study will explore the feasibility of home-based moderate-intensity exercise and ascertain its impact on metabolic and cardiovascular health in comparison to a lifestyle maintenance CON group. Findings from this study may help to inform new evidence-based physical activity guidelines and also help to elucidate the physiological mechanisms whereby exercise might exert beneficial effects in persons with chronic SCI. The results will also act as a scientific platform for further intervention studies in other diverse and at-risk populations. International Standard Randomised Controlled Trial Number: ISRCTN57096451 . Registered on 11 July 2014.

Testing the fetal overnutrition hypothesis; the relationship of maternal and paternal adiposity to adiposity, insulin resistance and cardiovascular risk factors in Indian children

PubMed Central

Veena, Sargoor R; Krishnaveni, Ghattu V; Karat, Samuel C; Osmond, Clive; Fall, Caroline HD

2012-01-01

Objective We aimed to test the fetal overnutrition hypothesis by comparing the associations of maternal and paternal adiposity (sum of skinfolds) with adiposity and cardiovascular risk factors in children. Design Children from a prospective birth cohort had anthropometry, fat percentage (bio-impedance), plasma glucose, insulin and lipid concentrations and blood pressure measured at 9·5 years of age. Detailed anthropometric measurements were recorded for mothers (at 30 ± 2 weeks’ gestation) and fathers (5 years following the index pregnancy). Setting Holdsworth Memorial Hospital, Mysore, India. Subjects Children (n 504), born to mothers with normal glucose tolerance during pregnancy. Results Twenty-eight per cent of mothers and 38 % of fathers were overweight/obese (BMI ≥ 25·0 kg/m2), but only 4 % of the children were overweight/obese (WHO age- and sex-specific BMI ≥ 18·2 kg/m2). The children’s adiposity (BMI, sum of skinfolds, fat percentage and waist circumference), fasting insulin concentration and insulin resistance increased with increasing maternal and paternal sum of skinfolds adjusted for the child’s sex, age and socio-economic status. Maternal and paternal effects were similar. The associations with fasting insulin and insulin resistance were attenuated after adjusting for the child’s current adiposity. Conclusions In this population, both maternal and paternal adiposity equally predict adiposity and insulin resistance in the children. This suggests that shared family environment and lifestyle, or genetic/epigenetic factors, influence child adiposity. Our findings do not support the hypothesis that there is an intrauterine overnutrition effect of maternal adiposity in non-diabetic pregnancies, although we cannot rule out such an effect in cases of extreme maternal obesity, which is rare in our population. PMID:22895107

Retinoic acid receptor-related orphan receptor α stimulates adipose tissue inflammation by modulating endoplasmic reticulum stress.

PubMed

Liu, Yin; Chen, Yulong; Zhang, Jinlong; Liu, Yulan; Zhang, Yanjie; Su, Zhiguang

2017-08-25

Adipose tissue inflammation has been linked to metabolic diseases such as obesity and type 2 diabetes. However, the molecules that mediate inflammation in adipose tissue have not been addressed. Although retinoic acid receptor-related orphan receptor α (RORα) is known to be involved in the regulation of inflammatory response in some tissues, its role is largely unknown in adipose tissue. Conversely, it is known that endoplasmic reticulum (ER) stress and unfolding protein response (UPR) signaling affect the inflammatory response in obese adipose tissue, but whether RORα regulates these processes remains unknown. In this study, we investigate the link between RORα and adipose tissue inflammation. We showed that the inflammatory response in macrophages or 3T3-L1 adipocytes stimulated by lipopolysaccharide, as well as adipose tissue in obese mice, markedly increased the expression of RORα. Adenovirus-mediated overexpression of RORα or treatment with the RORα-specific agonist SR1078 enhanced the expression of inflammatory cytokines and increased the number of infiltrated macrophages into adipose tissue. Furthermore, SR1078 up-regulated the mRNA expression of ER stress response genes and enhanced phosphorylations of two of the three mediators of major UPR signaling pathways, PERK and IRE1α. Finally, we found that alleviation of ER stress using a chemical chaperone followed by the suppression of RORα induced inflammation in adipose tissue. Our data suggest that RORα-induced ER stress response potentially contributes to the adipose tissue inflammation that can be mitigated by treatment with chemical chaperones. The relationships established here between RORα expression, inflammation, and UPR signaling may have implications for therapeutic targeting of obesity-related metabolic diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans.

PubMed

Brown, Amy; Hossain, Intekhab; Perez, Lester J; Nzirorera, Carine; Tozer, Kathleen; D'Souza, Kenneth; Trivedi, Purvi C; Aguiar, Christie; Yip, Alexandra M; Shea, Jennifer; Brunt, Keith R; Legare, Jean-Francois; Hassan, Ansar; Pulinilkunnil, Thomas; Kienesberger, Petra C

2017-01-01

Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients. LPA1-6 were expressed in myocardium and white adipose tissue from mice and humans, except for LPA3, which was undetectable in murine adipocytes and human adipose tissue. Obesity was associated with increased LPA4, LPA5 and/or LPA6 levels in mice ventricles and cardiomyocytes, HL-1 cells exposed to high palmitate, and human atrial tissue. LPA4 and LPA5 mRNA levels in human atrial tissue correlated with measures of obesity. LPA5 mRNA levels were increased in HFHS-fed mice and insulin resistant adipocytes, yet were reduced in adipose tissue from obese patients. LPA4, LPA5, and LPA6 mRNA levels in human adipose tissue were negatively associated with measures of obesity and cardiac surgery outcomes. This study suggests that obesity leads to marked changes in LPA receptor expression in the murine and human heart and white adipose tissue that may alter LPA receptor signaling during obesity.

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

PubMed

Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

2017-09-11

Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age

PubMed Central

Papandonatos, George D.; Calafat, Antonia M.; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P.; Yolton, Kimberly; Braun, Joseph M.

2017-01-01

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 PMID:28935615

Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity

USDA-ARS?s Scientific Manuscript database

Menopause, an age-related loss of ovarian hormone production, promotes increased adiposity and associated metabolic pathologies. However, the diet-independent mechanism(s) by which loss of ovarian function promotes increased adipose tissue mass and insulin resistance remain unclear. We investigate...

Fall and Fracture Risk in Sarcopenia and Dynapenia With and Without Obesity: the Role of Lifestyle Interventions.

PubMed

Scott, David; Daly, Robin M; Sanders, Kerrie M; Ebeling, Peter R

2015-08-01

Due to their differing etiologies and consequences, it has been proposed that the term "sarcopenia" should revert to its original definition of age-related muscle mass declines, with a separate term, "dynapenia", describing muscle strength and function declines. There is increasing interest in the interactions of sarcopenia and dynapenia with obesity. Despite an apparent protective effect of obesity on fracture, increased adiposity may compromise bone health, and the presence of sarcopenia and/or dynapenia ("sarcopenic obesity" and "dynapenic obesity") may exacerbate the risk of falls and fracture in obese older adults. Weight loss interventions are likely to be beneficial for older adults with sarcopenic and dynapenic obesity but may result in further reductions in muscle and bone health. The addition of exercise including progressive resistance training and nutritional strategies, including protein and vitamin D supplementation, may optimise body composition and muscle function outcomes thereby reducing falls and fracture risk in this population.

Independent Effects of Neighborhood Poverty and Psychosocial Stress on Obesity Over Time.

PubMed

Kwarteng, Jamila L; Schulz, Amy J; Mentz, Graciela B; Israel, Barbara A; Perkins, Denise White

2017-12-01

The objective of the study was to examine the independent effects of neighborhood poverty and psychosocial stress on increases in central adiposity over time. Data are from a community sample of 157 Non-Hispanic Black, Non-Hispanic White, and Hispanic adults collected in 2002-2003 and 2007-2008, and from the 2000 Decennial Census. The dependent variable was waist circumference. Independent variables included neighborhood poverty, perceived neighborhood physical environment, family stress, safety stress, everyday unfair treatment, and a cumulative stress index. Weighted 3-level hierarchical linear regression models for a continuous outcome were used to assess the effects of neighborhood poverty and psychosocial stress on central adiposity over time. We also assessed whether psychosocial stress mediated the association between neighborhood poverty and central adiposity. Neighborhood poverty and everyday unfair treatment at baseline were independently associated with increases in central adiposity over time, accounting for the other indicators of stress. Perceptions of the neighborhood physical environment and cumulative stress mediated associations between neighborhood poverty and central adiposity. Results suggest that residing in neighborhoods with higher concentrations of poverty and exposure to everyday unfair treatment independently heighten risk of increased central adiposity over time. Associations between neighborhood poverty and central adiposity were mediated by perceptions of the neighborhood physical environment and by the cumulative stress index. Public health strategies to reduce obesity should consider neighborhood poverty and exposure to multiple sources of psychosocial stress, including everyday unfair treatment.

The origins of adipose fins: an analysis of homoplasy and the serial homology of vertebrate appendages.

PubMed

Stewart, Thomas A; Smith, W Leo; Coates, Michael I

2014-04-22

Adipose fins are appendages found on the dorsal midline between the dorsal and caudal fins in more than 6000 living species of teleost fishes. It has been consistently argued that adipose fins evolved once and have been lost repeatedly across teleosts owing to limited function. Here, we demonstrate that adipose fins originated repeatedly by using phylogenetic and anatomical evidence. This suggests that adipose fins are adaptive, although their function remains undetermined. To test for generalities in the evolution of form in de novo vertebrate fins, we studied the skeletal anatomy of adipose fins across 620 species belonging to 186 genera and 55 families. Adipose fins have repeatedly evolved endoskeletal plates, anterior dermal spines and fin rays. The repeated evolution of fin rays in adipose fins suggests that these fins can evolve new tissue types and increased structural complexity by expressing fin-associated developmental modules in these new territories. Patterns of skeletal elaboration differ between the various occurrences of adipose fins and challenge prevailing hypotheses for vertebrate fin origin. Adipose fins represent a powerful and, thus far, barely studied model for exploring the evolution of vertebrate limbs and the roles of adaptation and generative biases in morphological evolution.

The origins of adipose fins: an analysis of homoplasy and the serial homology of vertebrate appendages

PubMed Central

Stewart, Thomas A.; Smith, W. Leo; Coates, Michael I.

2014-01-01

Adipose fins are appendages found on the dorsal midline between the dorsal and caudal fins in more than 6000 living species of teleost fishes. It has been consistently argued that adipose fins evolved once and have been lost repeatedly across teleosts owing to limited function. Here, we demonstrate that adipose fins originated repeatedly by using phylogenetic and anatomical evidence. This suggests that adipose fins are adaptive, although their function remains undetermined. To test for generalities in the evolution of form in de novo vertebrate fins, we studied the skeletal anatomy of adipose fins across 620 species belonging to 186 genera and 55 families. Adipose fins have repeatedly evolved endoskeletal plates, anterior dermal spines and fin rays. The repeated evolution of fin rays in adipose fins suggests that these fins can evolve new tissue types and increased structural complexity by expressing fin-associated developmental modules in these new territories. Patterns of skeletal elaboration differ between the various occurrences of adipose fins and challenge prevailing hypotheses for vertebrate fin origin. Adipose fins represent a powerful and, thus far, barely studied model for exploring the evolution of vertebrate limbs and the roles of adaptation and generative biases in morphological evolution. PMID:24598422

Anorexia Nervosa, Obesity and Bone Metabolism

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2014-01-01

Anorexia nervosa and obesity are conditions at the extreme ends of the nutritional spectrum, associated with marked reductions versus increases respectively in body fat content. Both conditions are also associated with an increased risk for fractures. In anorexia nervosa, body composition and hormones secreted or regulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, anorexia nervosa is characterized by increases in marrow adiposity and decreases in cold activated brown adipose tissue, both of which are related to low bone density. In obese individuals, greater visceral adiposity is associated with greater marrow fat, lower bone density and impaired bone structure. In this review, we discuss bone metabolism in anorexia nervosa and obesity in relation to adipose tissue distribution and hormones secreted or regulated by body fat content. PMID:24079076

Puberty is an important developmental period for the establishment of adipose tissue mass and metabolic homeostasis.

PubMed

Holtrup, Brandon; Church, Christopher D; Berry, Ryan; Colman, Laura; Jeffery, Elise; Bober, Jeremy; Rodeheffer, Matthew S

2017-07-03

Over the past 2 decades, the incidence of childhood obesity has risen dramatically. This recent rise in childhood obesity is particularly concerning as adults who were obese during childhood develop type II diabetes that is intractable to current forms of treatment compared with individuals who develop obesity in adulthood. While the mechanisms responsible for the exacerbated diabetic phenotype associated with childhood obesity is not clear, it is well known that childhood is an important time period for the establishment of normal white adipose tissue in humans. This association suggests that exposure to obesogenic stimuli during adipose development may have detrimental effects on adipose function and metabolic homeostasis. In this study, we identify the period of development associated with puberty, postnatal days 18-34, as critical for the establishment of normal adipose mass in mice. Exposure of mice to high fat diet only during this time period results in metabolic dysfunction, increased leptin expression, and increased adipocyte size in adulthood in the absence of sustained increased fat mass or body weight. These findings indicate that exposure to obesogenic stimuli during critical developmental periods have prolonged effects on adipose tissue function that may contribute to the exacerbated metabolic dysfunctions associated with childhood obesity.

Adipose tissue development during early life: novel insights into energy balance from small and large mammals.

PubMed

Symonds, Michael E; Pope, Mark; Budge, Helen

2012-08-01

Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.

Child adiposity and maternal feeding practices: a longitudinal analysis.

PubMed

Webber, Laura; Cooke, Lucy; Hill, Claire; Wardle, Jane

2010-12-01

Parental control has been hypothesized to cause weight gain in children by weakening self-regulatory processes. However, most studies that link control with weight have been cross-sectional, and therefore causation is uncertain. It remains possible that parental control is a response to child overweight rather than a cause. We investigated the direction of the association between parental feeding practices and children's adiposity in a longitudinal study. Three subscales of the Child Feeding Questionnaire (CFQ) that measure "pressure," "restriction," and "monitoring" were completed by 213 mothers of 7-9-y-old children as part of the Physical Exercise and Appetite in CHildren Study (PEACHES) and repeated by 113 mothers 3 y later. Baseline and follow-up anthropometric measurements [body mass index (BMI); fat mass index (FMI), and waist circumference (WC)] were made by researchers when the children were aged 7-9 y and 10-11 y. Regression analyses showed no association between any of the CFQ scales at baseline and change in child adiposity. In contrast, higher child BMI at baseline predicted a smaller decrease in follow-up CFQ "monitoring" (P = 0.003) and a larger decrease in "pressure to eat" (P = 0.04) after baseline scores were controlled for. Similar results were observed for FMI and WC, although they did not reach significance for WC. There were no significant longitudinal associations between child adiposity and the CFQ "restriction" subscale. The results were more consistent with a "child-responsive" model whereby a mother's choice of feeding practice is influenced by her child's weight status rather than her feeding practices influencing the child's weight gain.

Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity

USDA-ARS?s Scientific Manuscript database

Menopause promotes central obesity, adipose tissue (AT) inflammation and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages (M's), T-cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation an...

The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

DOE PAGES

Kim, Suyeon; Soltani-Bejnood, Morvarid; Quignard-Boulange, Annie; ...

2006-01-01

Background . The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results . A panel of mouse models including mice lacking angiotensinogen, Agt ( Agt -KO), mice expressing Agt solely in adipose tissue (aP2- Agt/Agt -KO), and mice overexpressing Agt in adipose tissue (aP2- Agt ) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt -KO mice, while plasma adiponectin levels were increased. aP2- Agt mice exhibited increased adiposity andmore » plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2- Agt mice. Conclusion . These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.« less

Studies on Human Adipose Cells in Culture: Relation of Cell Size and Cell Multiplication to Donor Age

PubMed Central

Adebonojo, Festus O.

1975-01-01

In an effort to test the adipose hyperplasia theory of obesity in humans, adipose cells, derived from anterior abdominal walls of human infants and children, were grown in synthetic medium (McCoy's 5A Medium) supplemented with 20% fetal calf serum. Adipose cells which became delipidinized in culture were found to be capable of division and the rate and number of cell divisions was age dependent. Cells of infants under 1 yr of age and cells derived from early adolescent children divided to varying degrees in culture. Adipose cells from children aged 1-10 yr showed no cell division. Cell division was never observed in a lipid-laden adipocyte. Measurements of cell diameter showed that after the first year of life, cell size increased progressively with age. During the first year adipose cell size appeared to reflect the rapid hyperplasia of the first 3 mo, reaching smallest size at 3-12 mo but increasing thereafter. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:124114

Biology and function of adipose tissue macrophages, dendritic cells and B cells.

PubMed

Ivanov, Stoyan; Merlin, Johanna; Lee, Man Kit Sam; Murphy, Andrew J; Guinamard, Rodolphe R

2018-04-01

The increasing incidence of obesity and its socio-economical impact is a global health issue due to its associated co-morbidities, namely diabetes and cardiovascular disease [1-5]. Obesity is characterized by an increase in adipose tissue, which promotes the recruitment of immune cells resulting in low-grade inflammation and dysfunctional metabolism. Macrophages are the most abundant immune cells in the adipose tissue of mice and humans. The adipose tissue also contains other myeloid cells (dendritic cells (DC) and neutrophils) and to a lesser extent lymphocyte populations, including T cells, B cells, Natural Killer (NK) and Natural Killer T (NKT) cells. While the majority of studies have linked adipose tissue macrophages (ATM) to the development of low-grade inflammation and co-morbidities associated with obesity, emerging evidence suggests for a role of other immune cells within the adipose tissue that may act in part by supporting macrophage homeostasis. In this review, we summarize the current knowledge of the functions ATMs, DCs and B cells possess during steady-state and obesity. Copyright © 2018 Elsevier B.V. All rights reserved.

IL-33 induces protective effects in adipose tissue inflammation during obesity in mice

PubMed Central

Miller, Ashley M.; Asquith, Darren L.; Hueber, Axel J.; Anderson, Lesley A.; Holmes, William M.; McKenzie, Andrew N.; Xu, Damo; Sattar, Naveed; McInnes, Iain B.; Liew, Foo Y.

2014-01-01

Rationale Chronic low-grade inflammation involving adipose tissue likely contributes to the metabolic consequences of obesity. The cytokine IL-33 and its receptor ST2 are expressed in adipose tissue but their role in adipose tissue inflammation during obesity is unclear. Objective To examine the functional role of IL-33 in adipose tissues, and investigate the effects on adipose tissue inflammation and obesity in vivo. Methods and Results We demonstrate that treatment of adipose tissue cultures in vitro with IL-33 induced production of Th2 cytokines (IL-5, IL-13, IL-10), and reduced expression of adipogenic and metabolic genes. Administration of recombinant IL-33 to genetically obese diabetic (ob/ob) mice led to reduced adiposity, reduced fasting glucose and improved glucose and insulin tolerance. IL-33 also induced accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages towards an M2 alternatively activated phenotype (CD206+), a lineage associated with protection against obesity-related metabolic events. Furthermore, mice lacking endogenous ST2 fed HFD had increased body weight and fat mass, impaired insulin secretion and glucose regulation compared to WT controls fed HFD. Conclusions In conclusion, IL-33 may play a protective role in the development of adipose tissue inflammation during obesity. PMID:20634488

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

PubMed

Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer Mi; Doh, Kyung-Oh; Hui, Chi-Chung; Sung, Hoon-Ki

2017-11-01

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

PubMed Central

Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer MI; Doh, Kyung-Oh; Hui, Chi-chung; Sung, Hoon-Ki

2017-01-01

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders. PMID:29039412

Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouadah-Boussouf, Nafia; Babin, Patrick J., E-mail: p.babin@gpp.u-bordeaux1.fr

One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adipositymore » in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.« less

Wound Healing and Angiogenesis through Combined Use of a Vascularized Tissue Flap and Adipose-Derived Stem Cells in a Rat Hindlimb Irradiated Ischemia Model.

PubMed

Yoshida, Shuhei; Yoshimoto, Hiroshi; Hirano, Akiyoshi; Akita, Sadanori

2016-05-01

Treatment of critical limb ischemia is sometimes difficult because of the patient's condition, and some novel approaches are needed. The hindlimbs of Sprague-Dawley rats, after 20-Gy x-ray irradiation and surgical occlusion, were divided into four groups: with a superficial fascial flap, 5.0 × 10 adipose-derived stromal/stem cells, and both combined. The rats were tested for laser tissue blood flow, immunohistologic blood vessel density, and foot paw punch hole wound healing. Green fluorescent protein-tagged Sprague-Dawley rats were used for further investigation by cell tracking for 2 weeks. Laser tissue blood flow demonstrated a significant increase in the combined treatment of flap and adipose-derived stem cells at both 1 and 2 weeks. There were no significant differences between the treatment groups treated with flaps alone and those treated with adipose-derived stem cells alone. Wound healing was significantly increased following combined treatment at 1 week, and there was no wound by 2 weeks except for the no-flap and no-adipose-derived stem cell group. The number of vessels depicted by von Willebrand factor showed a significant increase in the combined treatment group, at both 1 week and 2 weeks. In the cell tracking group, at 2 weeks, the green fluorescent protein-tagged adipose-derived stem cells were significantly more positive in the no-flap group than in the flap group. Adipose-derived stem cells may be a potent cell source in irradiated and occluded limbs by enhancing tissue blood flow and blood vessel density. Adipose-derived stem cells may play an important role in some difficult ischemic conditions in terms of wound healing.

Effects of chronic antipsychotic drug exposure on the expression of Translocator Protein and inflammatory markers in rat adipose tissue.

PubMed

Calevro, Anita; Cotel, Marie-Caroline; Natesan, Sridhar; Modo, Michel; Vernon, Anthony C; Mondelli, Valeria

2018-05-16

The precise effect of antipsychotic drugs on either central or peripheral inflammation remains unclear. An important issue in this debate is to what extent the known peripheral metabolic effects of antipsychotics, including increased adiposity, may contribute to increased inflammation. Adipose tissue is known to contribute to the development of systemic inflammation, which can eventually lead to insulin resistance and metabolic dysregulation. As a first step to address this question, we evaluated whether chronic exposure to clinically comparable doses of haloperidol or olanzapine resulted in the immune activation of rat adipose tissue. Samples of visceral adipose tissue were sampled from male Sprague-Dawley rats exposed to, haloperidol, olanzapine or vehicle (all n = 8), for 8 weeks. From these we measured a cytokine profile, protein expression of F4/80 (a phenotypic macrophage marker) and translocator protein (TSPO), a target for radiotracers putatively indicating microgliosis in clinical neuroimaging studies. Chronic olanzapine exposure resulted in significantly higher adipose IL-6 levels compared with vehicle-controls (ANOVA p = 0.008, Bonferroni post-hoc test p = 0.006); in parallel, animals exposed to olanzapine had significantly higher F4/80 expression when compared with vehicle-controls (Mann Whitney Test, p = 0.014), whereas there was no difference between haloperidol and vehicle groups (Mann Whitney test, p = 0.1). There were no significant effects of either drug on adipose TSPO protein levels. Nevertheless, we found a positive correlation between F4/80 and TSPO adipose protein levels in the olanzapine-exposed rats (Spearman's rho = 0.76, p = 0.037). Our data suggest that chronic exposure to olanzapine, but not haloperidol, increases production of the pro-inflammatory cytokine IL-6 in adipose tissue and increased macrophages expression (F4/80), in the absence of measurable changes in TSPO with respect to vehicle. This may have potentially important consequences in terms of metabolic dysregulation associated with long-term antipsychotic treatment. Copyright © 2018. Published by Elsevier Ltd.

Expression and Function of Myostatin in Obesity, Diabetes, and Exercise Adaptation

PubMed Central

Allen, David L.; Hittel, Dustin S.; McPherron, Alexandra C.

2011-01-01

Myostatin is a member of the transforming growth factor-beta/bone morphogenetic protein (TGF-β/BMP) super-family of secreted factors that functions as a potent inhibitor of skeletal muscle growth. Moreover, considerable evidence has accumulated that myostatin also regulates metabolism and that its inhibition can significantly attenuate the progression of obesity and diabetes. While at least part of these effects on metabolism can be attributable to myostatin’s influence over skeletal muscle growth and therefore on the total volume of metabolically active lean body mass, there is mounting evidence that myostatin affects the growth and metabolic state of other tissues, including the adipose and the liver. In addition, recent work has explored the role of myostatin in substrate mobilization, uptake and/or utilization of muscle independent of its effects on body composition. Finally, the effects of both endurance and resistance exercise on myostatin expression, as well as the potential role of myostatin in the beneficial metabolic adaptations occurring in response to exercise, have also begun to be delineated in greater detail. The purpose of this review is to summarize the work to date on the expression and function of myostatin in obesity, diabetes, and exercise adaptation. PMID:21364474

Expression and function of myostatin in obesity, diabetes, and exercise adaptation.

PubMed

Allen, David L; Hittel, Dustin S; McPherron, Alexandra C

2011-10-01

Myostatin is a member of the transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) superfamily of secreted factors that functions as a potent inhibitor of skeletal muscle growth. Moreover, considerable evidence has accumulated that myostatin also regulates metabolism and that its inhibition can significantly attenuate the progression of obesity and diabetes. Although at least part of these effects on metabolism can be attributable to myostatin's influence over skeletal muscle growth and therefore on the total volume of metabolically active lean body mass, there is mounting evidence that myostatin affects the growth and metabolic state of other tissues, including the adipose and the liver. In addition, recent work has explored the role of myostatin in substrate mobilization, uptake, and/or utilization of muscle independent of its effects on body composition. Finally, the effects of both endurance and resistance exercise on myostatin expression, as well as the potential role of myostatin in the beneficial metabolic adaptations occurring in response to exercise, have also begun to be delineated in greater detail. The purpose of this review was to summarize the work to date on the expression and function of myostatin in obesity, diabetes, and exercise adaptation.

Impairment of nutritional regulation of adipose triglyceride lipase expression with age.

PubMed

Caimari, A; Oliver, P; Palou, A

2008-08-01

Fasting-induced lipolysis becomes less effective with age. We have studied whether nutritional regulation of adipose triglyceride lipase (ATGL)--with an important role in lipolysis in low energy states--is affected by age. Wistar rats of different ages (from 1 to 13 months) were distributed in control and fasted groups (14 h-food deprivation). ATGL mRNA expression was measured in different adipose depots at different ages and in only one depot at 13 months by reverse transcription (RT)-PCR. ATGL protein levels were determined at 3 and 7 months (not at 13 months) by western blot. Nonesterified fatty acid (NEFA), insulin and leptin levels were assessed in serum by enzymatic assays. ATGL expression was dependent on regional fat distribution, with higher levels in brown than in white adipose tissue depots; and was affected by age: ATGL mRNA was increased with age in the brown adipose tissue and was decreased in two of the studied white depots, the inguinal and retroperitoneal, not being affected in the epididymal and mesenteric. Age also affected ATGL nutritional regulation: fasting increased ATGL gene expression and protein levels in the different white adipose depots of the youngest rats (up to the age of 5 months), whereas there was no change in the oldest rats studied (7 and 13-months old). This was in agreement with the pattern of NEFA levels, which did not increase in serum of fasted rats in the oldest animals, whereas other homeostatic parameters, such as insulin and leptin, responded to fasting independently of age. ATGL expressed by brown adipose tissue was not affected by feeding conditions at any age. Nutritional regulation of ATGL expression in white adipose tissue is impaired with age, which could contribute to the increased difficulty for mobilizing lipids when animals are exposed to nutritional stress such as fasting.

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats.

PubMed

Granados, N; Amengual, J; Ribot, J; Musinovic, H; Ceresi, E; von Lintig, J; Palou, A; Bonet, M L

2013-09-01

To assess the influence of supplementation with a moderate dose of vitamin A in early life on adipose tissue development and the response to an obesogenic diet later in life. During the suckling period, rat pups received a daily oral dose of retinyl palmitate corresponding to three times the vitamin A ingested daily from maternal milk. Control rats received the vehicle (olive oil). Short-term effects of treatment on gene expression and morphology of white adipose tissue (WAT) were analyzed in animals on the day after weaning (day 21). To study long-term effects, control and vitamin A-treated rats were fed, after weaning, a normal fat or a high-fat (HF) diet for 16 weeks. WAT of vitamin A-treated young rats (day 21) was enriched in small adipocytes with a reduced expression of adipogenic markers (peroxisome proliferator-activated receptor γ and lipoprotein lipase) and an increased cell proliferation potential as indicated by increased expression of proliferating cell nuclear antigen. Increased retinoic acid (RA)-induced transcriptional responses were present in the tissues of vitamin A-treated young rats (day 21) including WAT. Vitamin A-treated rats developed higher adiposity than control rats on a HF diet as indicated by body composition analysis and increased WAT depot mass, adipocyte diameter, WAT DNA content, leptinemia and adipose leptin gene expression. Excess adiposity gain in vitamin A-treated rats developed in the absence of changes in body weight and was attributable to excess adipocyte hyperplasia. No differences in adiposity were observed between vitamin A-treated rats and control rats on a normal fat diet. Total retinol levels in WAT of vitamin A-treated rats were elevated at weaning (day 21) and normalized by day 135 of age. Vitamin A intake in the early stages of postnatal life favors subsequent HF diet-induced adiposity gain through mechanisms that may relate to changes in adipose tissue development, likely mediated by RA.

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

PubMed

Achard, V; Tassistro, V; Boullu-Ciocca, S; Grino, M

2011-12-01

Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice

PubMed Central

Subramanian, Savitha; Han, Chang Yeop; Chiba, Tsuyoshi; McMillen, Timothy S.; Wang, Shari A.; Haw, Antonio; Kirk, Elizabeth A.; O’Brien, Kevin D.; Chait, Alan

2009-01-01

Objective Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. Methods and Results LDLR-/- mice were fed chow, high fat, high carbohydrate (diabetogenic) diet without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation and local inflammation were observed in intra-abdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. Conclusions Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation and increased atherosclerosis in this mouse model. PMID:18239153

Homeobox a5 Promotes White Adipose Tissue Browning Through Inhibition of the Tenascin C/Toll-Like Receptor 4/Nuclear Factor Kappa B Inflammatory Signaling in Mice.

PubMed

Cao, Weina; Huang, Hongtao; Xia, Tianyu; Liu, Chenlong; Muhammad, Saeed; Sun, Chao

2018-01-01

Lipopolysaccharide (LPS) induces rapid increase in systemic inflammatory factors. As adipose tissue is a key contributor to the inflammatory response to numerous metabolic stimuli, it is important to understand the mechanism behind the LPS-induced inflammation in white adipose tissue (WAT). Homeobox a5 (Hoxa5) is an important transcription factor, which is highly expressed in adipose tissue, and its mRNA expression is increased at cold exposure in mice. So far, the function of Hoxa5 in adipose tissue browning has been poorly understood. So, the objective of this study was conducted to determine the role of Hoxa5 in adipose inflammatory response and white adipose browning in mice. LPS-induced inflammatory and cold-induced browning model were conducted. We compared the coordinated role of Hoxa5 in inflammation and thermogenesis of mice adipose. Transcriptional and methylation regulation was determined by luciferase assay, electrophoretic mobility shift assay, and bisulfite conversion experiment. Hoxa5 and tenascin C (TNC) were involved in WAT inflammation and browning in mice with LPS injection. Furthermore, Hoxa5 inhibited the TNC-involved activation of Toll-like receptor (TLR) 4/nuclear factor kappa B (NF-κB) signal pathway and promoted WAT browning. Moreover, we found that a BMP4/Smad1 signal, closely related to browning, was activated by Hoxa5. Hoxa5 relieved adipocyte inflammation by decreasing TNC-mediated TLR4 transducer and activator of the NF-κB pathway. Interestingly, descended methylation level increased Hoxa5 expression in cold exposure. Our findings demonstrated that Hoxa5 alleviated inflammation and enhanced browning of adipose tissue via negative control of TNC/TLR4/NF-κB inflammatory signaling and activating BMP4/Smad1 pathway. These findings indicated a novel potential means for the regulation of inflammation in adipocytes to prevent obesity and other inflammatory diseases.

Paternal physical exercise demethylates the hippocampal DNA of male pups without modifying the cognitive and physical development.

PubMed

Mega, Filipe; de Meireles, André Luís Ferreira; Piazza, Francele Valente; Spindler, Christiano; Segabinazi, Ethiane; Dos Santos Salvalaggio, Gabriela; Achaval, Matilde; Marcuzzo, Simone

2018-08-01

Maternal exercise is known to have beneficial effects in progeny development, but the influence of paternal exercise on the offspring still unclear. Since spermatogenesis is a continuous process, the father's life experiences can reprogram epigenetic content of the sperm and somehow interfere on offspring phenotype. This study was designed to evaluate the effects of paternal physical exercise on cognitive and physical development and on hippocampal DNA methylation levels of the offspring. Adult male Wistar rats were divided into two groups: sedentary and exercised. The exercise protocol occurred before mating and consisted of treadmill running, 5 consecutive days/week for 8 weeks (20 min/day). The mothers were not trained. The following developmental parameters were examined in male offspring: body growth, physical and cognitive performance, weights of adrenal glands, gonadal fat and hindlimb muscles, BDNF expression and global DNA methylation at the hippocampus. The progeny of trained and sedentary fathers did not differ in relation to physical parameters and performance, spatial memory and BDNF expression. However, paternal exercise promoted a decrease in offspring´s relative gonadal fat weight and a lower percentage of global hippocampal DNA methylation compared to offspring of sedentary fathers. These results pointed to interference of male physical activity at the time of conception on adiposity and hippocampal epigenetic reprogramming of male offspring. The data reinforces that exercise does not harm the descendant's development and emphasize the benefits to include the practice of physical exercise in a healthier lifestyle of the parents. Nevertheless, future studies are necessary and should investigate further the long-effects of epigenetic mechanisms in order to elucidate the father's contribution in fetal programming. Copyright © 2018 Elsevier B.V. All rights reserved.

The Effect of Lipoaspirates on Human Keratinocytes.

PubMed

Kim, Bong-Sung; Gaul, Charel; Paul, Nora E; Dewor, Manfred; Stromps, Jan-Philipp; Hwang, Soo Seok; Nourbakhsh, Mahtab; Bernhagen, Jürgen; Rennekampff, Hans-Oliver; Pallua, Norbert

2016-09-01

One increasingly important trend in plastic, reconstructive, and aesthetic surgery is the use of fat grafts to improve cutaneous wound healing. In clinical practice, lipoaspirates (adipose tissue harvested by liposuction) are re-injected in a procedure called lipofilling. Previous studies, however, mainly evaluated the regenerative effect of isolated adipocytes, adipose-derived stem cells, and excised en bloc adipose tissue on keratinocytes, whereas no study to date has examined the effect of lipoaspirates. The authors aimed to investigate differences in the regenerative property of en bloc adipose tissue and lipoaspirates on keratinocytes. Human keratinocytes, lipoaspirates, and en bloc adipose tissue from 36 healthy donors were isolated. In vitro proliferation, differentiation, migration, stratification, and wound healing of keratinocyte monolayers were measured. Furthermore, secreted levels of VEGF, bFGF, IGF-1, MMP-9, and MIF were detected by ELISA. Migration, proliferation, and wound healing of keratinocytes were increased by lipoaspirates. Interestingly, the effect of lipoaspirates on keratinocyte proliferation was significantly higher than by en bloc adipose tissue after 5 days. The differentiation of keratinocytes was equally attenuated by lipoaspirates and en bloc adipose tissue. Stratification of keratinocyte layers was enhanced by lipoaspirates and en bloc fat when compared to controls. Lipoaspirates secrete higher levels of bFGF, whereas higher levels of VEGF and IGF-1 are released by en bloc adipose tissue. We show that lipoaspirates and en bloc adipose tissue have a regenerative effect on keratinocytes. One reason for the higher effect of lipoaspirates on keratinocyte proliferation may be the secretion of different cytokines. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet

PubMed Central

2014-01-01

Background Obesity has been studied as a metabolic and an inflammatory disease and is characterized by increases in the production of pro-inflammatory adipokines in the adipose tissue. To elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity. Materials/methods Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data. Results The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-α ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-α ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of IκBα and HSLser660 in adipose tissue. Conclusions Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes. PMID:24495336

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

PubMed Central

Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

2012-01-01

Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet.

PubMed

Dias, Fernando Milanez; Leffa, Daniela Dimer; Daumann, Francine; Marques, Schérolin de Oliveira; Luciano, Thais F; Possato, Jonathan Correa; de Santana, Aline Alves; Neves, Rodrigo Xavier; Rosa, José Cesar; Oyama, Lila Missae; Rodrigues, Bruno; de Andrade, Vanessa Moraes; de Souza, Cláudio Teodoro; de Lira, Fabio Santos

2014-02-04

Obesity has been studied as a metabolic and an inflammatory disease and is characterized by increases in the production of pro-inflammatory adipokines in the adipose tissue.To elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity. Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data. The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-α ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-α ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of IκBα and HSLser660 in adipose tissue. Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes.

Performance comparison of the MOXY and PortaMon near-infrared spectroscopy muscle oximeters at rest and during exercise

NASA Astrophysics Data System (ADS)

McManus, Chris J.; Collison, Jay; Cooper, Chris E.

2018-01-01

The purpose of the study was to compare muscle oxygenation as measured by two portable, wireless near-infrared spectroscopy (NIRS) devices under resting and dynamic conditions. A recently developed low-cost NIRS device (MOXY) was compared against an established PortaMon system that makes use of the spatially resolved spectroscopy algorithm. The influence of increasing external pressure on tissue oxygen saturation index (TSI) indicated that both devices are stable between 2 and 20 mmHg. However, above this pressure, MOXY reports declining TSI values. Analysis of adipose tissue thickness (ATT) and TSI shows a significant, nonlinear difference between devices at rest. The devices report similar TSI (%) values at a low ATT (<7 mm) (PortaMon minus MOXY difference is +1.1±2.8%) with the major subsequent change between the devices occurring between 7 and 10 mm at ATT values >10 mm the difference remains constant (-14.7±2.8%). The most likely explanation for this difference is the small source-detector separation (2.5 cm) in the MOXY resulting in lower tissue penetration into muscle in subjects with higher ATT. Interday test-retest reliability of resting TSI was evaluated on five separate occasions, with the PortaMon reporting a lower coefficient of variation (1.8% to 2.5% versus 5.7% to 6.2%). In studies on male subjects with low ATT, decreases in the TSI were strongly correlated during isometric exercise, arterial occlusion, and incremental arm crank exercise. However, the MOXY reports a greater dynamic range, particularly during ischemia induced by isometric contraction or occlusion (Δ74.3% versus Δ43.7% hyperemia MAX-occlusion MIN). This study shows that in this subject group both MOXY and PortaMon produce physiologically credible TSI measures during rest and exercise. However, the absolute values obtained during exercise are generally not comparable between devices unless corrected by physiological calibration following an arterial occlusion.

BAIBA Does Not Regulate UCP-3 Expression in Human Skeletal Muscle as a Response to Aerobic Exercise.

PubMed

Morales, Flor E; Forsse, Jeffrey S; Andre, Thomas L; McKinley-Barnard, Sarah K; Hwang, Paul S; Anthony, Ian G; Tinsley, Grant M; Spillane, Mike; Grandjean, Peter W; Ramirez, Alejandro; Willoughby, Darryn S

2017-01-01

β-Aminoisobutyric acid (BAIBA) has shown to modulate uncoupling protein (UCP)-1 expression, which is mainly expressed in white adipose tissue; however, no studies to date have analyzed its potential effect on the main uncoupling protein of skeletal muscle, UCP-3. The main goal of this study was to assess the potential effect of acute aerobic exercise on serum BAIBA and skeletal muscle UCP-3. The secondary goal was to assess the potential involvement of the transcription factors proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor alpha (PPARα), as well as free fatty acids (FFAs) in UCP-3 expression. A tertiary goal of the study was to evaluate the potential effect of consuming a preexercise meal on the outcome of the first 2 objectives. In a randomized crossover design, untrained participants performed 2 acute cycling sessions (350 kcal at 70% of their VO 2peak ) after 2 experimental conditions: (1) consumption of a multi-macronutrient shake and (2) a fasting period of 8 hours. Blood samples were taken at baseline, preexercise, postexercise, 1 hour, and 4 hours postexercise, and muscle biopsies were taken at the last 4 time points. UCP-3 protein concentration and expression, as well as the mRNA expression of PGC-1α and PPARα, were measured in muscle, and BAIBA, glucose, and FFA were measured in serum. Aerobic exercise failed to induce a significant effect on serum BAIBA, PGC-1α, and PPARα regardless on the feeding condition. Despite the lack of effect of exercise on the previous variables, UCP-3 expression and protein concentration significantly increased in the shake condition. The expression of human skeletal muscle UCP-3 as a result of exercise might be controlled by factors other than BAIBA.

MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice.

PubMed

Ballak, Dov B; van Essen, Peter; van Diepen, Janna A; Jansen, Henry; Hijmans, Anneke; Matsuguchi, Tetsuya; Sparrer, Helmut; Tack, Cees J; Netea, Mihai G; Joosten, Leo A B; Stienstra, Rinke

2014-01-01

Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8). Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD) for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1β, IL-6 and IL-8, but not TNF -α, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1β, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1β and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance.

Estrogenic phytochemicals reduce bone adiposity and improves bone quality following ovariectomy.

EPA Science Inventory

Menopause causes increased adiposity and the risk of osteoporosis. Partly as a result of the carcinogenic concerns of hormone replacement therapy, increasing numbers of post-menopausal women are taking botanical and dietary supplements to manage these adverse body composition cha...

Developmental Programming: Impact of Prenatal Testosterone Excess on Insulin Sensitivity, Adiposity, and Free Fatty Acid Profile in Postpubertal Female Sheep

PubMed Central

Veiga-Lopez, A.; Moeller, J.; Patel, D.; Ye, W.; Pease, A.; Kinns, J.

2013-01-01

Prenatal T excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested whether increases in visceral adiposity, adipocyte size, and total free fatty acids underlie the insulin resistance seen in prenatal T-treated female sheep. At approximately 16 months of age, insulin resistance and adipose tissue partitioning were determined via hyperinsulinemic euglycemic clamp and computed tomography, respectively, in control and prenatal T-treated females. Three months later, adipocyte size and free fatty acid composition were determined. Results revealed that at the postpubertal time points tested, insulin sensitivity was increased, visceral adiposity and adipocyte size in both the sc and the visceral compartments were reduced, and circulating palmitic acid was increased in prenatal T-treated females relative to controls. In parallel studies, 20-month-old prenatal T-treated females tended to have increased basal insulin to glucose ratio. Relative to earlier findings of reduced insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in free fatty acid metabolism a few months later correspond to a time point when the insulin sensitivity indices of prenatal T-treated animals appear to shift toward insulin resistance. In summary, current findings of improved insulin sensitivity and reduced visceral adiposity in postpubertal prenatal T-treated sheep relative to our earlier findings of reduced insulin sensitivity during early postnatal life and adulthood are indicative of a period of developmental adaptation. PMID:23525243

Aerobic Exercise for Reducing Migraine Burden: Mechanisms, Markers, and Models of Change Processes

PubMed Central

Irby, Megan B.; Bond, Dale S.; Lipton, Richard B.; Nicklas, Barbara; Houle, Timothy T.; Penzien, Donald B.

2016-01-01

Background Engagement in regular exercise routinely is recommended as an intervention for managing and preventing migraine, and yet empirical support is far from definitive. We possess at best a weak understanding of how aerobic exercise and resulting change in aerobic capacity influence migraine, let alone the optimal parameters for exercise regimens as migraine therapy (eg, who will benefit, when to prescribe, optimal types, and doses/intensities of exercise, level of anticipated benefit). These fundamental knowledge gaps critically limit our capacity to deploy exercise as an intervention for migraine. Overview Clear articulation of the markers and mechanisms through which aerobic exercise confers benefits for migraine would prove invaluable and could yield insights on migraine pathophysiology. Neurovascular and neuroinflammatory pathways, including an effect on obesity or adiposity, are obvious candidates for study given their role both in migraine as well as the changes known to accrue with regular exercise. In addition to these biological pathways, improvements in aerobic fitness and migraine alike also are mediated by changes in psychological and sociocognitive factors. Indeed a number of specific mechanisms and pathways likely are operational in the relationship between exercise and migraine improvement, and it remains to be established whether these pathways operate in parallel or synergistically. As heuristics that might conceptually benefit our research programs here forward, we: (1) provide an extensive listing of potential mechanisms and markers that could account for the effects of aerobic exercise on migraine and are worthy of empirical exploration and (2) present two exemplar conceptual models depicting pathways through which exercise may serve to reduce the burden of migraine. Conclusion Should the promise of aerobic exercise as a feasible and effective migraine therapy be realized, this line of endeavor stands to benefit migraineurs (including the many who presently remain suboptimally treated) by providing a new therapeutic avenue as an alternative or augmentative compliment to established interventions for migraine. PMID:26643584

Aerobic Exercise for Reducing Migraine Burden: Mechanisms, Markers, and Models of Change Processes.

PubMed

Irby, Megan B; Bond, Dale S; Lipton, Richard B; Nicklas, Barbara; Houle, Timothy T; Penzien, Donald B

2016-02-01

Engagement in regular exercise routinely is recommended as an intervention for managing and preventing migraine, and yet empirical support is far from definitive. We possess at best a weak understanding of how aerobic exercise and resulting change in aerobic capacity influence migraine, let alone the optimal parameters for exercise regimens as migraine therapy (eg, who will benefit, when to prescribe, optimal types, and doses/intensities of exercise, level of anticipated benefit). These fundamental knowledge gaps critically limit our capacity to deploy exercise as an intervention for migraine. Clear articulation of the markers and mechanisms through which aerobic exercise confers benefits for migraine would prove invaluable and could yield insights on migraine pathophysiology. Neurovascular and neuroinflammatory pathways, including an effect on obesity or adiposity, are obvious candidates for study given their role both in migraine as well as the changes known to accrue with regular exercise. In addition to these biological pathways, improvements in aerobic fitness and migraine alike also are mediated by changes in psychological and sociocognitive factors. Indeed a number of specific mechanisms and pathways likely are operational in the relationship between exercise and migraine improvement, and it remains to be established whether these pathways operate in parallel or synergistically. As heuristics that might conceptually benefit our research programs here forward, we: (1) provide an extensive listing of potential mechanisms and markers that could account for the effects of aerobic exercise on migraine and are worthy of empirical exploration and (2) present two exemplar conceptual models depicting pathways through which exercise may serve to reduce the burden of migraine. Should the promise of aerobic exercise as a feasible and effective migraine therapy be realized, this line of endeavor stands to benefit migraineurs (including the many who presently remain suboptimally treated) by providing a new therapeutic avenue as an alternative or augmentative compliment to established interventions for migraine. © 2015 American Headache Society.

Fasting energy homeostasis in mice with adipose deficiency of desnutrin/adipose triglyceride lipase.

PubMed

Wu, Jiang Wei; Wang, Shu Pei; Casavant, Stéphanie; Moreau, Alain; Yang, Gong She; Mitchell, Grant A

2012-05-01

Adipose triglyceride lipase (ATGL) catalyzes the first step of lipolysis of cytoplasmic triacylglycerols in white adipose tissue (WAT) and several other organs. We created adipose-specific ATGL-deficient (ATGLAKO) mice. In these mice, in vivo lipolysis, measured as the increase of plasma nonesterified fatty acid and glycerol levels after injection of a β3-adrenergic agonist, was undetectable. In isolated ATGLAKO adipocytes, β3-adrenergic-stimulated glycerol release was 10-fold less than in controls. Under fed conditions, ATGLAKO mice had normal viability, mild obesity, low plasma nonesterified fatty acid levels, increased insulin sensitivity, and increased daytime food intake. After 5 h of fasting, ATGLAKO WAT showed phosphorylation of the major protein kinase A-mediated targets hormone-sensitive lipase and perilipin A and ATGLAKO liver showed low glycogen and triacylglycerol contents. During a 48-h fast, ATGLAKO mice developed striking and complex differences from controls: progressive reduction of oxygen consumption, high respiratory exchange ratio, consistent with reduced fatty acid availability for energy production, lethargy, hypothermia, and undiminished fat mass, but greater loss of lean mass than controls. Plasma of 48 h-fasted ATGLAKO mice had a unique pattern: low 3-hydroxybutyrate, insulin, adiponectin, and fibroblast growth factor 21 with elevated leptin and corticosterone. ATGLAKO WAT, liver, skeletal muscle, and heart showed increased levels of mRNA related to autophagy and proteolysis. In murine ATGL deficiency, adipose lipolysis is critical for fasting energy homeostasis, and fasting imposes proteolytic stress on many organs, including heart and skeletal muscle.

Trends in adiposity in Brazilian 7-10-year-old schoolchildren: evidence for increasing overweight but not obesity between 2002 and 2007.

PubMed

Leal, Danielle Biazzi; de Assis, Maria Alice Altenburg; González-Chica, David Alejandro; da Costa, Filipe Ferreira

2014-01-01

The negative health consequences of childhood overweight/obesity (OW/OB) are well known. Therefore, an accurate monitoring of the OW/OB prevalence is essential. Anthropometry is the most practical and cost-effective method for nutritional status evaluation. To describe trends in the nutritional status among 7-10-year-old children by investigating changes in the prevalence of stunting, thinness, overweight, obesity, risk and excess abdominal adiposity, and to study changes in height-for-age, body mass index (BMI) and waist circumference (WC). A school-based sample of 7-10-year-old children participated in two cross-sectional studies in 2002 (n = 2936) and 2007 (n = 1232) in Florianopolis, southern Brazil. Prevalence of stunting, risk and excess abdominal adiposity and changes in the distribution of height-for-age, BMI-for-age, WC-for-age z-scores were evaluated. Three BMI-based references were used to define the prevalence of thinness, overweight and obesity. Between 2002-2007, the prevalence of stunting, thinness, obesity and excess abdominal adiposity remained stable, whereas overweight (including obesity) increased 10-23% in boys and 18-21% in girls, depending on the BMI reference used. The risk of abdominal adiposity increased in boys, but not in girls. No significant change was observed in mean height, BMI, WC-for-age z-scores. This study identified a potential levelling off in the prevalence of obesity and excess abdominal adiposity, but a continuing increase in the prevalence of overweight.

Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510; Yoshizaki, Takayuki

2011-11-11

Highlights: Black-Right-Pointing-Pointer Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. Black-Right-Pointing-Pointer Adipose lipin-1 expression is reduced in obesity. Black-Right-Pointing-Pointer Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. Black-Right-Pointing-Pointer Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytesmore » by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-{kappa}B activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.« less

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

PubMed

Ishii, Makoto; Iadecola, Costantino

2016-05-01

Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function.

PubMed

Carli, Jayne F Martin; LeDuc, Charles A; Zhang, Yiying; Stratigopoulos, George; Leibel, Rudolph L

2018-02-21

Genetic variants within the FTO (α-ketoglutarate-dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as a result of increased food intake. These risk alleles are associated with decreased expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein 1 like). RPGRIP1L encodes a protein that is critical to the function of the primary cilium, which conveys extracellular information to the cell. Rpgrip1l +/- mice exhibit increased adiposity, in part, as a result of hyperphagia. Here, we describe the effects of Rpgrip1l in adipocytes that may contribute to the adiposity phenotype observed in these animals and possibly in humans who segregate for FTO risk alleles. Loss of Rpgrip1l in 3T3-L1 preadipocytes increased the number of cells that are capable of differentiating into mature adipocytes. Knockout of Rpgrip1l in mature adipocytes using Adipoq-Cre did not increase adiposity in mice that were fed chow or a high-fat diet. We also did not observe any effects of Rpgrip1l knockdown in mature 3T3-L1 adipocytes. Thus, to the extent that Rpgrip1l affects cell-autonomous adipose tissue function, it may do so as a result of the effects conveyed in preadipocytes in which the primary cilium is functionally important. We propose that decreased RPGRIP1L expression in preadipocytes in humans who segregate for FTO obesity risk alleles may increase the storage capacity of adipose tissue.-Martin Carli, J. F., LeDuc, C. A., Zhang, Y., Stratigopoulos, G., Leibel, R. L. The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function.

Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring

USDA-ARS?s Scientific Manuscript database

Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. However, it is not known whether maternal undernutrition increases ATM phenotypic expression in F1 offspring. Us...

Alterations in energy balance from an exercise intervention with ad libitum food intake.

PubMed

Melzer, Katarina; Renaud, Anne; Zurbuchen, Stefanie; Tschopp, Céline; Lehmann, Jan; Malatesta, Davide; Ruch, Nicole; Schutz, Yves; Kayser, Bengt; Mäder, Urs

2016-01-01

Better understanding is needed regarding the effects of exercise alone, without any imposed dietary regimens, as a single tool for body-weight regulation. Thus, we evaluated the effects of an 8-week increase in activity energy expenditure (AEE) on ad libitum energy intake (EI), body mass and composition in healthy participants with baseline physical activity levels (PAL) in line with international recommendations. Forty-six male adults (BMI = 19·7-29·3 kg/m(2)) participated in an intervention group, and ten (BMI = 21·0-28·4 kg/m(2)) in a control group. Anthropometric measures, cardiorespiratory fitness, EI, AEE and exercise intensity were recorded at baseline and during the 1st, 5th and 8th intervention weeks, and movement was recorded throughout. Body composition was measured at the beginning and at the end of the study, and resting energy expenditure was measured after the study. The intervention group increased PAL from 1·74 (se 0·03) to 1·93 (se 0·03) (P < 0·0001) and cardiorespiratory fitness from 41·4 (se 0·9) to 45·7 (se 1·1) ml O2/kg per min (P = 0·001) while decreasing body mass (-1·36 (se 0·2) kg; P = 0·001) through adipose tissue mass loss (ATM) (-1·61 (se 0·2) kg; P = 0·0001) compared with baseline. The control group did not show any significant changes in activity, body mass or ATM. EI was unchanged in both groups. The results indicate that in normal-weight and overweight men, increasing PAL from 1·7 to 1·9 while keeping EI ad libitum over an 8-week period produces a prolonged negative energy balance. Replication using a longer period (and/or more intense increase in PAL) is needed to investigate if and at what body composition the increase in AEE is met by an equivalent increase in EI.

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile

PubMed Central

Swisher, Anne K.; Abraham, Jame; Bonner, Daniel; Gilleland, Diana; Hobbs, Gerald; Kurian, Sobha; Yanosik, Mary Anne; Vona-Davis, Linda

2015-01-01

Purpose Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been testing specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. Methods Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy—Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). Results Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p<0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p<0.05). Conclusions Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program. PMID:25724409

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

PubMed

Swisher, Anne K; Abraham, Jame; Bonner, Daniel; Gilleland, Diana; Hobbs, Gerald; Kurian, Sobha; Yanosik, Mary Anne; Vona-Davis, Linda

2015-10-01

Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05). Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program.

Interrelations among the adipocytokines leptin and adiponectin, oxidative stress and aseptic inflammation markers in pre- and early-pubertal normal-weight and obese boys.

PubMed

Paltoglou, George; Schoina, Maria; Valsamakis, George; Salakos, Nicolaos; Avloniti, Alexandra; Chatzinikolaou, Athanasios; Margeli, Alexandra; Skevaki, Chrysanthi; Papagianni, Maria; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Chrousos, George P; Fatouros, Ioannis G; Mastorakos, George

2017-03-01

Presumed interrelationships among deleterious aspects of adipose tissue metabolism, inflammation, and cellular oxidative stress could be influenced by pubertal hormonal changes. They were investigated in pre- and early pubertal normal-weight and obese boys before and after an exercise bout employed as an energy demanding stimulator. Cross-sectional study. Seventy-six healthy pre- (mean ± SD, 10.6 ± 0.2 years old, 28 normal-weight, and 11 obese) and early-(11.4 ± 0.2 years old, 25 normal-weight, and 12 obese) pubertal boys, were blood-sampled before and after a bout of exercise at 70% VO 2 max. Leptin, adiponectin, markers of inflammation (high-sensitivity C-reactive protein, high sensitivity IL-6), pro- (thiobarbitouric acid reactive substances, protein carbonyls) and anti- (glutathione, oxidized glutathione, glutathione peroxidase, catalase, total antioxidant capacity) oxidation were measured. Baseline and post-exercise adiponectin was greater and leptin and high-sensitivity C-reactive protein were lower in normal-weight than in obese pre- and early pubertal boys, while high sensitivity IL-6 was greater in obese than in normal-weight pre-pubertal boys. In pre-pubertal obese boys: at baseline, high-sensitivity C-reactive protein correlated negatively with catalase; high sensitivity IL-6 correlated positively with protein carbonyls; Δ (difference during exercise) adiponectin correlated positively with Δcatalase. In all boys: at baseline, high sensitivity IL-6 correlated positively with leptin and was the best negative and the second best positive predictor for post-exercise glutathione/oxidized glutathione and protein carbonyls, respectively; leptin was the best negative predictor for post-exercise glutathione; waist to height ratio was the best positive predictor for post-exercise thiobarbitouric acid reactive substances; body mass index z-score and adiponectin were, respectively, the best positive predictor for post-exercise protein carbonyls and catalase. In all subjects, leptin and adiponectin predict negatively and positively anti-oxidation, respectively, while high sensitivity IL-6 predicts positively and negatively pro- and anti-oxidation, respectively. High-sensitivity C-reactive protein is increased and negatively associated with anti-oxidation in pre-pubertal obese boys, suggesting that childhood obesity is associated with aseptic inflammation and oxidative stress.

Fat accumulation in the tongue is associated with male gender, abnormal upper airway measures and whole-body adiposity

PubMed Central

Godoy, Ivan R. B.; Martinez-Salazar, Edgar Leonardo; Eajazi, Alireza; Genta, Pedro R.; Bredella, Miriam A.; Torriani, Martin

2017-01-01

Objective To examine associations between tongue adiposity with upper airway measures, whole-body adiposity and gender. We hypothesized that increased tongue adiposity is higher in males and positively associated with abnormal upper airway measures and whole-body adiposity. Methods We studied subjects who underwent whole-body positron emission tomography/computed tomography to obtain tongue attenuation (TA) values and cross-sectional area, pharyngeal length (PL) and mandibular-hyoid distance (MPH), as well as abdominal circumference, abdominal subcutaneous and visceral (VAT) adipose tissue areas, neck circumference (NC) and neck adipose tissue area. Metabolic syndrome was determined from available clinical and laboratory data. Results We identified 206 patients (104 females, 102 males) with mean age 56±17y and mean body mass index (BMI) 28±6kg/m2 (range 16–47kg/m2). Males had lower TA values (P=0.0002) and higher upper airway measures (P< 0.0001) independent of age and BMI (P<0.001). In all subjects, TA was negatively associated with upper airway measures (P<0.001). TA was negatively associated with body composition parameters (all P<0.0001), most notably with VAT (r=−0.53) and NC (r=−0.47). TA values were lower in subjects with metabolic syndrome (P<0.0001). Conclusion Increased tongue adiposity is influenced by gender and is associated with abnormal upper airway patency and body composition parameters. PMID:27733254

Fat accumulation in the tongue is associated with male gender, abnormal upper airway patency and whole-body adiposity.

PubMed

Godoy, Ivan R B; Martinez-Salazar, Edgar Leonardo; Eajazi, Alireza; Genta, Pedro R; Bredella, Miriam A; Torriani, Martin

2016-11-01

To examine associations between tongue adiposity with upper airway measures, whole-body adiposity and gender. We hypothesized that increased tongue adiposity is higher in males and positively associated with abnormal upper airway measures and whole-body adiposity. We studied subjects who underwent whole-body positron emission tomography/computed tomography to obtain tongue attenuation (TA) values and cross-sectional area, pharyngeal length (PL) and mandibular plane to hyoid distance (MPH), as well as abdominal circumference, abdominal subcutaneous and visceral (VAT) adipose tissue areas, neck circumference (NC) and neck adipose tissue area. Metabolic syndrome was determined from available clinical and laboratory data. We identified 206 patients (104 females, 102 males) with mean age 56±17years and mean body mass index (BMI) 28±6kg/m 2 (range 16-47kg/m 2 ). Males had lower TA values (P=0.0002) and higher upper airway measures (P<0.0001) independent of age and BMI (P<0.001). In all subjects, TA was negatively associated with upper airway measures (P<0.001). TA was negatively associated with body composition parameters (all P<0.0001), most notably with VAT (r=-0.53) and NC (r=-0.47). TA values were lower in subjects with metabolic syndrome (P<0.0001). Increased tongue adiposity is influenced by gender and is associated with abnormal upper airway patency and body composition parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of hypokinesia on lipid metabolism in adipose tissue

NASA Astrophysics Data System (ADS)

Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

Plasticity of adipose tissue in response to fasting and refeeding in male mice.

PubMed

Tang, Hao-Neng; Tang, Chen-Yi; Man, Xiao-Fei; Tan, Shu-Wen; Guo, Yue; Tang, Jun; Zhou, Ci-La; Zhou, Hou-De

2017-01-01

Fasting is the most widely prescribed and self-imposed strategy for treating excessive weight gain and obesity, and has been shown to exert a number of beneficial effects. The aim of the present study was to determine the exact role of fasting and subsequent refeeding on fat distribution in mice. C57/BL6 mice fasted for 24 to 72 h and were then subjected to refeeding for 72 h. At 24, 48 and 72 h of fasting, and 12, 24, 48 and 72 h of refeeding, the mice were sacrificed, and serum and various adipose tissues were collected. Serum biochemical parameters, adipose tissue masses and histomorphological analysis of different depots were detected. MRNA was isolated from various adipose tissues, and the expressions of thermogenesis, visceral signature and lipid metabolism-related genes were examined. The phenotypes of adipose tissues between juvenile and adult mice subjected to fasting and refeeding were also compared. Fasting preferentially consumed mesenteric fat mass and decreased the cell size of mesenteric depots; however, refeeding recovered the mass and morphology of inguinal adipose tissues preferentially compared with visceral depots. Thermogenesis-related gene expression in the inguinal WAT and interscapular BAT were suppressed. Mitochondrial biogenesis was affected by fasting in a depot-specific manner. Furthermore, a short period of fasting led to an increase in visceral signature genes ( Wt1, Tcf21 ) in subcutaneous adipose tissue, while the expression of these genes decreased sharply as the fasting time increased. Additionally, lipogenesis-related markers were enhanced to a greater extent greater in subcutaneous depots compared with those in visceral adipose tissues by refeeding. Although similar phenotypic changes in adipose tissue were observed between juvenile mice and adult mice subjected to fasting and refeeding, the alterations appeared earlier and more sensitively in juvenile mice. Fasting preferentially consumes lipids in visceral adipose tissues, whereas refeeding recovers lipids predominantly in subcutaneous adipose tissues, which indicated the significance of plasticity of adipose organs for fat distribution when subject to food deprivation or refeeding.

Prolonged fasting activates hypoxia inducible factor -1α, -2α and -3α in a tissue-specific manner in northern elephant seal pups

PubMed Central

Soñanez-Organis, José G.; Vázquez-Medina, José P.; Crocker, Daniel E.; Ortiz, Rudy M.

2013-01-01

Hypoxia inducible factors (HIFs) are important regulators of energy homeostasis and cellular adaptation to low oxygen conditions. Northern elephant seals are naturally adapted to prolonged periods (1–2 months) of food deprivation (fasting) that result in metabolic changes that may activate HIF-1. However, the effects of prolonged fasting on HIFs are not well defined. We obtained the full-length cDNAs of HIF-1α and HIF-2α, and partial cDNA of HIF-3α in northern elephant seal pups. We also measured mRNA and nuclear protein content of HIF-1α, -2α, -3α in muscle and adipose during prolonged fasting (1, 3, 5 & 7 wks), along with mRNA expression of HIF-mediated genes, LDH and VEGF. HIF-1α, -2α and -3α are 2595, 2852 and 1842 bp and encode proteins of 823, 864 and 586 amino acid residues with conserved domains needed for their function (bHLH and PAS) and regulation (ODD and TAD). HIF-1α and -2α mRNA expression increased 3- to 5-fold after 7 weeks of fasting in adipose and muscle, whereas HIF-3α increased 5-fold after 7 weeks of fasting in adipose. HIF-2α protein expression was detected in nuclear fractions from adipose and muscle, increasing approximately 2-fold, respectively with fasting. Expression of VEGF increased 3-fold after 7 weeks in adipose and muscle, whereas LDH mRNA expression increased 12-fold after 7 weeks in adipose. While the 3 HIFα genes are expressed in muscle and adipose, only HIF-2α protein was detectable in the nucleus suggesting that HIF-2α may contribute more significantly in the up-regulation of genes involved in the metabolic adaption during fasting in the elephant seal. PMID:23707926

Prolonged fasting activates hypoxia inducible factors-1α, -2α and -3α in a tissue-specific manner in northern elephant seal pups.

PubMed

Soñanez-Organis, José G; Vázquez-Medina, José P; Crocker, Daniel E; Ortiz, Rudy M

2013-09-10

Hypoxia inducible factors (HIFs) are important regulators of energy homeostasis and cellular adaptation to low oxygen conditions. Northern elephant seals are naturally adapted to prolonged periods (1-2 months) of food deprivation (fasting) which result in metabolic changes that may activate HIF-1. However, the effects of prolonged fasting on HIFs are not well defined. We obtained the full-length cDNAs of HIF-1α and HIF-2α, and partial cDNA of HIF-3α in northern elephant seal pups. We also measured mRNA and nuclear protein content of HIF-1α, -2α, -3α in muscle and adipose during prolonged fasting (1, 3, 5 & 7 weeks), along with mRNA expression of HIF-mediated genes, LDH and VEGF. HIF-1α, -2α and -3α are 2595, 2852 and 1842 bp and encode proteins of 823, 864 and 586 amino acid residues with conserved domains needed for their function (bHLH and PAS) and regulation (ODD and TAD). HIF-1α and -2α mRNA expression increased 3- to 5-fold after 7 weeks of fasting in adipose and muscle, whereas HIF-3α increased 5-fold after 7 weeks of fasting in adipose. HIF-2α protein expression was detected in nuclear fractions from adipose and muscle, increasing approximately 2-fold, respectively with fasting. Expression of VEGF increased 3-fold after 7 weeks in adipose and muscle, whereas LDH mRNA expression increased 12-fold after 7 weeks in adipose. While the 3 HIFα genes are expressed in muscle and adipose, only HIF-2α protein was detectable in the nucleus suggesting that HIF-2α may contribute more significantly in the up-regulation of genes involved in the metabolic adaptation during fasting in the elephant seal. Copyright © 2013 Elsevier B.V. All rights reserved.

Impact of adiposity on cellular adhesion: The Multi-Ethnic Study of atherosclerosis (MESA).

PubMed

Christoph, Mary J; Allison, Matthew A; Pankow, James S; Decker, Paul A; Kirsch, Phillip S; Tsai, Michael Y; Sale, Michele M; de Andrade, Mariza; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q; Berardi, Cecilia; Wassel, Christina L; Larson, Nicholas B; Bielinski, Suzette J

2016-01-01

At the cellular level, how excess adiposity promotes atherogenesis is not fully understood. One pathway involves secretion of adipokines that stimulate endothelial dysfunction through increased expression of adhesion molecules. However, the relationship of adiposity to adhesion molecules that promote atherosclerosis is largely unknown. Linear regression models were used to assess the sex-specific associations of soluble cellular adhesion molecules (sP- and sL-selectin, sICAM-1, sVCAM-1, and sHGF) and adiposity in 5,974 adults examined as part of the Multi-Ethnic Study of Atherosclerosis (MESA). Adiposity measures included body mass index (BMI), waist-to-hip-ratio (WHR), and computed tomography measures of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The mean age was 64 years and 52% were female. In multivariable models adjusting for traditional cardiovascular risk factors, sHGF was positively associated with BMI, WHR, and VAT in both males and females, and sP-selectin with WHR and VAT in males. sVCAM-1 was inversely associated with VAT in females only. Our results showed the relation of adiposity to soluble cellular adhesion proteins was similar across adiposity measures and for both sexes. However, the relationship between adiposity and sVCAM-1 and P-selectin may be modified by sex and the measure used to assess adiposity. © 2015 The Obesity Society.

Classification of different degrees of adiposity in sedentary rats.

PubMed

Leopoldo, A S; Lima-Leopoldo, A P; Nascimento, A F; Luvizotto, R A M; Sugizaki, M M; Campos, D H S; da Silva, D C T; Padovani, C R; Cicogna, A C

2016-01-01

In experimental studies, several parameters, such as body weight, body mass index, adiposity index, and dual-energy X-ray absorptiometry, have commonly been used to demonstrate increased adiposity and investigate the mechanisms underlying obesity and sedentary lifestyles. However, these investigations have not classified the degree of adiposity nor defined adiposity categories for rats, such as normal, overweight, and obese. The aim of the study was to characterize the degree of adiposity in rats fed a high-fat diet using cluster analysis and to create adiposity intervals in an experimental model of obesity. Thirty-day-old male Wistar rats were fed a normal (n=41) or a high-fat (n=43) diet for 15 weeks. Obesity was defined based on the adiposity index; and the degree of adiposity was evaluated using cluster analysis. Cluster analysis allowed the rats to be classified into two groups (overweight and obese). The obese group displayed significantly higher total body fat and a higher adiposity index compared with those of the overweight group. No differences in systolic blood pressure or nonesterified fatty acid, glucose, total cholesterol, or triglyceride levels were observed between the obese and overweight groups. The adiposity index of the obese group was positively correlated with final body weight, total body fat, and leptin levels. Despite the classification of sedentary rats into overweight and obese groups, it was not possible to identify differences in the comorbidities between the two groups.

Employee adiposity and incivility: establishing a link and identifying demographic moderators and negative consequences.

PubMed

Sliter, Katherine A; Sliter, Michael T; Withrow, Scott A; Jex, Steve M

2012-10-01

The prevalence of increased adiposity among employees in the American workplace has resulted in significant economic costs to organizations. Unfortunately, relatively little research has examined the effects of excess adiposity on employees themselves. As a step toward remedying this, the current study examined a previously unknown link between adiposity and incivility, and how this might impact employee burnout and withdrawal. A student sample was used to initially establish a link between incivility and adiposity, and an applied sample of employees from across the United States was used to more fully test the relationships among incivility, adiposity, burnout, and withdrawal. Finally, the moderating effects of sex and race on these relationships were examined. Preliminary data from 341 student employees revealed that being overly adipose was related to greater reports of workplace incivility, with the effect strongest for those classified as obese. An interaction between sex and adiposity was also found, as well as a three-way interaction among sex, race, and adiposity. These relationships were replicated using a nationwide sample of 528 full-time employees. An interaction between race and adiposity was also found in this second sample. Finally, a model was tested in which incivility was shown to partially mediate the positive relationship between adiposity and the outcome of withdrawal, with both sex and race acting as moderators. Theoretical and practical implications of the findings and future directions are discussed.

Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome.

PubMed

Roerink, Sean H P P; Wagenmakers, Margreet A E M; Langenhuijsen, Johan F; Ballak, Dov B; Rooijackers, Hanne M M; d'Ancona, Frank C; van Dielen, François M; Smit, Jan W A; Plantinga, Theo S; Netea-Maier, Romana T; Hermus, Ad R M M

2017-08-01

To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile. © 2017 The Obesity Society.

Increased consumption of dairy foods and protein during diet- and exercise-induced weight loss promotes fat mass loss and lean mass gain in overweight and obese premenopausal women.

PubMed

Josse, Andrea R; Atkinson, Stephanie A; Tarnopolsky, Mark A; Phillips, Stuart M

2011-09-01

Weight loss can have substantial health benefits for overweight or obese persons; however, the ratio of fat:lean tissue loss may be more important. We aimed to determine how daily exercise (resistance and/or aerobic) and a hypoenergetic diet varying in protein and calcium content from dairy foods would affect the composition of weight lost in otherwise healthy, premenopausal, overweight, and obese women. Ninety participants were randomized to 3 groups (n = 30/group): high protein, high dairy (HPHD), adequate protein, medium dairy (APMD), and adequate protein, low dairy (APLD) differing in the quantity of total dietary protein and dairy food-source protein consumed: 30 and 15%, 15 and 7.5%, or 15 and <2% of energy, respectively. Body composition was measured by DXA at 0, 8, and 16 wk and MRI (n = 39) to assess visceral adipose tissue (VAT) volume at 0 and 16 wk. All groups lost body weight (P < 0.05) and fat (P < 0.01); however, fat loss during wk 8-16 was greater in the HPHD group than in the APMD and APLD groups (P < 0.05). The HPHD group gained lean tissue with a greater increase during 8-16 wk than the APMD group, which maintained lean mass and the APLD group, which lost lean mass (P < 0.05). The HPHD group also lost more VAT as assessed by MRI (P < 0.05) and trunk fat as assessed by DXA (P < 0.005) than the APLD group. The reduction in VAT in all groups was correlated with intakes of calcium (r = 0.40; P < 0.05) and protein (r = 0.32; P < 0.05). Therefore, diet- and exercise-induced weight loss with higher protein and increased dairy product intakes promotes more favorable body composition changes in women characterized by greater total and visceral fat loss and lean mass gain.

Sex-dependent effects of neonatal maternal deprivation on endocannabinoid levels in the adipose tissue: influence of diet.

PubMed

Mela, Virginia; Piscitelli, Fabiana; Berzal, Alvaro Llorente; Chowen, Julie; Silvestri, Cristoforo; Viveros, Maria Paz; Di Marzo, Vincenzo

2016-08-01

Maternal deprivation (MD) during neonatal life has diverse long-term effects, including modification of metabolism. We have previously reported that MD modifies the metabolic response to high-fat diet (HFD) intake, with this response being different between males and females, while previous studies indicate that in mice with HFD-induced obesity, endocannabinoid (EC) levels are markedly altered in various brown and white adipose tissue depots. Here, we analyzed the effects of MD (24 h at postnatal day 9), alone or in combination with a HFD from weaning until the end of the experiment in Wistar rats of both sexes. Brown and white perirenal and subcutaneous adipose tissues were collected and the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) were determined. In males, MD increased the content of OEA in brown and 2-AG in subcutaneous adipose tissues, while in females the content of 2-AG was increased in perirenal fat. Moreover, in females, MD decreased AEA and OEA levels in perirenal and subcutaneous adipose tissues, respectively. HFD decreased the content of 2-AG in brown fat of both sexes and OEA in brown and subcutaneous adipose tissue of control females. In contrast, in subcutaneous fat, HFD increased AEA levels in MD males and OEA levels in control and MD males. The present results show for the first time that MD and HFD induce sex-dependent effects on the main ECs, AEA, and 2-AG, and of AEA-related mediators, OEA and PEA, in the rat brown and white (visceral and subcutaneous) adipose tissues.