A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice

PubMed Central

Grove, KL; Fried, SK; Greenberg, AS; Xiao, XQ; Clegg, DJ

2013-01-01

Objective A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose tissue and gene expression, comparing differentially expressed genes in diet-induced obese mice with mice maintained on a chow diet. Research Design and Methods We used a microarray approach to determine whether there are sexual dimorphisms in gene expression in age-matched male, female or ovariectomized female (OVX) C57/BL6 mice maintained on a high-fat (HF) diet. We then compared expression of validated genes between the sexes on a chow diet. Results After exposure to a high fat diet for 12 weeks, females gained less weight than males. The microarray analyses indicate in intra-abdominal/gonadal adipose tissue in females 1642 genes differ by at least twofold between the depots, whereas 706 genes differ in subcutaneous/inguinal adipose tissue when compared with males. Only 138 genes are commonly regulated in both sexes and adipose tissue depots. Inflammatory genes (cytokine–cytokine receptor interactions and acute-phase protein synthesis) are upregulated in males when compared with females, and there is a partial reversal after OVX, where OVX adipose tissue gene expression is more ′male-like′. This pattern is not observed in mice maintained on chow. Histology of male gonadal white adipose tissue (GWAT) shows more crown-like structures than females, indicative of inflammation and adipose tissue remodeling. In addition, genes related to insulin signaling and lipid synthesis are higher in females than males, regardless of dietary exposure. Conclusions These data suggest that male and female adipose tissue differ between the sexes regardless of diet. Moreover, HF diet exposure elicits a much greater inflammatory response in males when compared with females. This data set underscores the importance of analyzing depot-, sex- and steroid-dependent regulation of adipose tissue distribution and function. PMID:20157318

Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway

USDA-ARS?s Scientific Manuscript database

The goal was to examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), Beta-cell function, and SAT gene expression. SAT biopsies were obtained from...

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

Validating skinfold thickness as a proxy to estimate total body fat in wild toque macaques (Macaca sinica) using the mass of dissected adipose tissue.

PubMed

Dittus, Wolfgang P J; Gunathilake, K A Sunil

2015-06-01

Skinfold thickness (SFT) has been used often in non-human primates and humans as a proxy to estimate fatness (% body fat). We intended to validate the relation between SFT (in recently deceased specimens) and the mass of adipose tissue as determined from dissection of fresh carcasses of wild toque macaques (Macaca sinica). In adult male and female toque macaques body composition is normally 2% adipose tissue. Calipers for measuring SFT were suitable for measuring only some subcutaneous deposits of adipose tissue but were not suitable for measuring large fat deposits within the body cavity or minor intermuscular ones. The anatomical distribution of 13 different adipose deposits, in different body regions (subcutaneous, intra-abdominal and intermuscular) and their proportional size differences, were consistent in this species (as in other primates), though varying in total mass among individuals. These consistent allometric relationships were fundamental for estimating fatness of different body regions based on SFT. The best fit statistically significant correlations and regressions with the known masses of dissectible adipose tissue were evident between the SFT means of the seven sites measured, as well as with a single point on the abdomen anterior to the umbilicus. SFT related to total fat mass and intra-abdominal fat mass in curvilinear regressions and to subcutaneous fat mass in a linear relationship. To adjust for differences in body size among individuals, and to circumvent intangible variations in total body mass allocated, for example to the gastro-intestinal contents, dissected fat mass was estimated per unit body size (length of crown-rump)(3). SFT had greater coefficients of correlation and regressions with this Fat Mass Index (g/dm(3)) than with Percent Body Fat. © 2015 Wiley Periodicals, Inc.

Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

PubMed Central

Forney, Laura A.; Lenard, Natalie R.; Stewart, Laura K.

2018-01-01

Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms. PMID:29562620

High-Fat Diet-Induced Adiposity, Adipose Inflammation, Hepatic Steatosis and Hyperinsulinemia in Outbred CD-1 Mice

PubMed Central

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population. PMID:25768847

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

PubMed

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

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.

Differential CT Attenuation of Metabolically Active and Inactive Adipose Tissues — Preliminary Findings

PubMed Central

Hu, Houchun H.; Chung, Sandra A.; Nayak, Krishna S.; Jackson, Hollie A.; Gilsanz, Vicente

2010-01-01

This study investigates differences in CT Hounsfield units (HUs) between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. PET/CT data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified and standard uptake values (SUVs) and HUs were measured. HUs of active brown fat were more positive (p<0.001) than inactive fat (−62.4±5.3 versus −86.7±7.0) and the difference was observed in both males and females. PMID:21245691

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

PubMed

Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

2017-08-01

Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet. © 2016 Japanese Society of Animal Science.

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

Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

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

Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui

Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration ofmore » SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.« less

Characterization of Visceral and Subcutaneous Adipose Tissue Transcriptome and Biological Pathways in Pregnant and Non-Pregnant Women: Evidence for Pregnancy-Related Regional-Specific Differences in Adipose Tissue

PubMed Central

Mazaki-Tovi, Shali; Vaisbuch, Edi; Tarca, Adi L.; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Romero, Roberto

2015-01-01

Objective The purpose of this study was to compare the transcriptome of visceral and subcutaneous adipose tissues between pregnant and non-pregnant women. Study Design The transcriptome of paired visceral and abdominal subcutaneous adipose tissues from pregnant women at term and matched non-pregnant women (n = 11) was profiled with the Affymetrix Human Exon 1.0 ST array. Differential expression of selected genes was validated with the use of quantitative reverse transcription–polymerase chain reaction. Results Six hundred forty-four transcripts from 633 known genes were differentially expressed (false discovery rate (FDR) <0.1; fold-change >1.5), while 42 exons from 36 genes showed differential usage (difference in FIRMA scores >2 and FDR<0.1) between the visceral and subcutaneous fat of pregnant women. Fifty-six known genes were differentially expressed between pregnant and non-pregnant subcutaneous fat and three genes in the visceral fat. Enriched biological processes in the subcutaneous adipose tissue of pregnant women were mostly related to inflammation. Conclusion The transcriptome of visceral and subcutaneous fat depots reveals pregnancy-related gene expression and splicing differences in both visceral and subcutaneous adipose tissue. Furthermore, for the first time, alternative splicing in adipose tissue has been associated with regional differences and human parturition. PMID:26636677

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

Increased adipose tissue lipolysis after a 2-week high-fat diet in sedentary overweight/obese men.

PubMed

Howe, Harold R; Heidal, Kimberly; Choi, Myung Dong; Kraus, Ray M; Boyle, Kristen; Hickner, Robert C

2011-07-01

The purpose of this study was to determine if a high-fat diet would result in a higher lipolytic rate in subcutaneous adipose tissue than a lower-fat diet in sedentary nonlean men. Six participants (healthy males; 18-40 years old; body mass index, 25-37 kg/m(2)) underwent 2 weeks on a high-fat or well-balanced diet of similar energy content (approximately 6695 kJ) in randomized order with a 10-day washout period between diets. Subcutaneous abdominal adipose tissue lipolysis was determined over the course of a day using microdialysis after both 2-week diet sessions. Average interstitial glycerol concentrations (index of lipolysis) as determined using microdialysis were higher after the high-fat diet (210.8 ± 27.9 μmol/L) than after a well-balanced diet (175.6 ± 23.3 μmol/L; P = .026). There was no difference in adipose tissue microvascular blood flow as determined using the microdialysis ethanol technique. These results demonstrate that healthy nonlean men who diet on the high-fat plan have a higher lipolytic rate in subcutaneous abdominal adipose tissue than when they diet on a well-balanced diet plan. This higher rate of lipolysis may result in a higher rate of fat mass loss on the high-fat diet; however, it remains to be determined if this higher lipolytic rate in men on the high-fat diet results in a more rapid net loss of triglyceride from the abdominal adipose depots, or if the higher lipolytic rate is counteracted by an increased rate of lipid storage. Copyright © 2011 Elsevier Inc. All rights reserved.

Increased adipose tissue lipolysis after a two-week high-fat diet in sedentary overweight/obese men

PubMed Central

Howe, Harold R; Heidal, Kimberly; Choi, Myung Dong; Kraus, Ray M.; Boyle, Kristen; Hickner, Robert C.

2013-01-01

Background/Objectives The purpose of this study was to determine if a high fat diet would result in a higher lipolytic rate in subcutaneous adipose tissue than a lower fat diet in sedentary non-lean men. Subjects/Methods Six participants (healthy males: 18-40 yrs old: body mass index 25-37 kg/m2) underwent two weeks on a high-fat or well-balanced diet of similar caloric content (approx. 1600 kcal) in randomized order with a ten-day washout period between diets. Subcutaneous abdominal adipose tissue lipolysis was determined over the course of a day using microdialysis after both two-week diet sessions. Results Average interstitial glycerol concentrations (index of lipolysis) as determined using microdialysis were higher following the high-fat diet (210.8 ±27.9 μM) than following a well-balanced diet (175.6 ± 23.3 μM; P = 0.026). There was no difference in adipose tissue microvascular blood flow as determined using the microdialysis ethanol technique. Conclusions These results demonstrate that healthy non-lean men who diet on the high-fat plan have a higher lipolytic rate in subcutaneous abdominal adipose tissue than when they diet on a well-balanced diet plan. This higher rate of lipolysis may result in a higher rate of fat mass loss on the high-fat diet; however, it remains to be determined if this higher lipolytic rate in men on the high-fat diet results in a more rapid net loss of triglyceride from the abdominal adipose depots, or if the higher lipolytic rate is counteracted by an increased rate of lipid storage. PMID:21040937

LXR activation by GW3965 alters fat tissue distribution and adipose tissue inflammation in ob/ob female mice[S

PubMed Central

Archer, Amena; Stolarczyk, Émilie; Doria, Maria Luisa; Helguero, Luisa; Domingues, Rosário; Howard, Jane K.; Mode, Agneta; Korach-André, Marion; Gustafsson, Jan-Åke

2013-01-01

To investigate the role of liver X receptor (LXR) in adipose tissue metabolism during obesity, ob/ob mice were treated for 5 weeks with the synthetic LXR agonist GW3965. MRI analysis revealed that pharmacological activation of LXR modified fat distribution by decreasing visceral (VS) fat and inversely increasing subcutaneous (SC) fat storage without affecting whole body fat content. This was concordant with opposite regulation by GW3965 of the lipolytic markers hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in the two fat depots; moreover, the expression of genes involved in lipogenesis was significantly induced in SC fat. Lipidomic analysis suggested that changes in lipid composition in response to GW3965 also varied between VS and SC fat. In both depots, the observed alteration in lipid composition indicated an overall change toward less lipotoxic lipids. Flow cytometry analysis showed decreased immune cell infiltration in adipose tissue of ob/ob mice in response to GW3965 treatment, which in VS fat mainly affected the macrophage population and in SC fat the lymphocyte population. In line with this, the expression and secretion of proinflammatory markers was decreased in both fat deposits with GW3965 treatment. PMID:23446231

Detrimental and protective fat: body fat distribution and its relation to metabolic disease.

PubMed

Booth, Andrea; Magnuson, Aaron; Foster, Michelle

2014-01-01

Obesity is linked to numerous comorbidities that include, but are not limited to, glucose intolerance, insulin resistance, dyslipidemia, and cardiovascular disease. Current evidence suggests, however, obesity itself is not an exclusive predictor of metabolic dysregulation but rather adipose tissue distribution. Obesity-related adverse health consequences occur predominately in individuals with upper body fat accumulation, the detrimental distribution, commonly associated with visceral obesity. Increased lower body subcutaneous adipose tissue, however, is associated with a reduced risk of obesity-induced metabolic dysregulation and even enhanced insulin sensitivity, thus, storage in this region is considered protective. The proposed mechanisms that causally relate the differential outcomes of adipose tissue distribution are often attributed to location and/or adipocyte regulation. Visceral adipose tissue effluent to the portal vein drains into the liver where hepatocytes are directly exposed to its metabolites and secretory products, whereas the subcutaneous adipose tissue drains systemically. Adipose depots are also inherently different in numerous ways such as adipokine release, immunity response and regulation, lipid turnover, rate of cell growth and death, and response to stress and sex hormones. Proximal extrinsic factors also play a role in the differential drive between adipose tissue depots. This review focuses on the deleterious mechanisms postulated to drive the differential metabolic response between central and lower body adipose tissue distribution.

Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue in Patients With and Without Antiretroviral Therapy–Associated Lipodystrophy

PubMed Central

Sevastianova, Ksenia; Sutinen, Jussi; Greco, Dario; Sievers, Meline; Salmenkivi, Kaisa; Perttilä, Julia; Olkkonen, Vesa M.; Wågsäter, Dick; Lidell, Martin E.; Enerbäck, Sven; Eriksson, Per; Walker, Ulrich A.; Auvinen, Petri; Ristola, Matti; Yki-Järvinen, Hannele

2011-01-01

OBJECTIVE Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1–infected cART-treated patients with (cART+LD+) and without (cART+LD−) lipodystrophy. RESEARCH DESIGN AND METHODS We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n = 21) and cART+LD− (n = 11). RESULTS Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD−. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes. PMID:21602514

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

Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

PubMed

Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

2016-06-08

Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

Regulation of the Fibrosis and Angiogenesis Promoter SPARC/Osteonectin in Human Adipose Tissue by Weight Change, Leptin, Insulin, and Glucose

PubMed Central

Kos, Katrina; Wong, Steve; Tan, Bee; Gummesson, Anders; Jernas, Margareta; Franck, Niclas; Kerrigan, David; Nystrom, Fredrik H.; Carlsson, Lena M.S.; Randeva, Harpal S.; Pinkney, Jonathan H.; Wilding, John P.H.

2009-01-01

OBJECTIVE Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 ± 3.7 kg). Another six lean subjects underwent fast-food–based hyperalimentation for 4 weeks (weight gain: 7.2 ± 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment–insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity. PMID:19509023

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

PubMed Central

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-01-01

Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R2=0.751, P<0.001). Conclusions: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance. PMID:26563815

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

PubMed

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-04-01

Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes.

PubMed

Chiu, Chen-Yuan; Chan, Im-Lam; Yang, Tsung-Han; Liu, Shing-Hwa; Chiang, Meng-Tsan

2015-03-25

This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel.

PubMed

Gonçalves, Pedro; Magro, Fernando; Martel, Fátima

2015-02-01

Epidemiological studies show that both the incidence of inflammatory bowel disease (IBD) and the proportion of people with obesity and/or obesity-associated metabolic syndrome increased markedly in developed countries during the past half century. Obesity is also associated with the development of more active IBD and requirement for hospitalization and with a decrease in the time span between diagnosis and surgery. Patients with IBD, especially Crohn's disease, present fat-wrapping or "creeping fat," which corresponds to ectopic adipose tissue extending from the mesenteric attachment and covering the majority of the small and large intestinal surface. Mesenteric adipose tissue in patients with IBD presents several morphological and functional alterations, e.g., it is more infiltrated with immune cells such as macrophages and T cells. All these lines of evidence clearly show an association between obesity, adipose tissue, and functional bowel disorders. In this review, we will show that the mesenteric adipose tissue and creeping fat are not innocent by standers but actively contribute to the intestinal and systemic inflammatory responses in patients with IBD. More specifically, we will review evidence showing that adipose tissue in IBD is associated with major alterations in the secretion of cytokines and adipokines involved in inflammatory process, in adipose tissue mesenchymal stem cells and adipogenesis, and in the interaction between adipose tissue and other intestinal components (immune, lymphatic, neuroendocrine, and intestinal epithelial systems). Collectively, these studies underline the importance of adipose tissue for the identification of novel therapeutic approaches for IBD.

Flow cytometry on the stromal-vascular fraction of white adipose tissue

USDA-ARS?s Scientific Manuscript database

Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow c...

Fat from contused adipose tissue may cause yellow discoloration of clothes in blunt trauma victims.

PubMed

Geisenberger, D; Wuest, F; Bielefeld, L; Große Perdekamp, M; Pircher, R; Pollak, S; Thierauf-Emberger, A; Huppertz, L M

2014-12-01

In some fatalities from intense blunt trauma, the victims' clothes show strikingly yellow discoloration being in topographic correspondence with lacerated skin and crush damage to the underlying fatty tissue. This phenomenon is especially pronounced in light-colored textiles such as underwear made of cotton and in the absence of concomitant blood-staining. The constellation of findings seems to indicate that the fabric has been soaked with liquid body fat deriving from the contused adipose tissue. To check this hypothesis, textiles suspected to be contaminated with fat were investigated in 6 relevant cases. GC-MS-analysis proved the presence of 11 fatty acids. The fatty acid composition was similar to that of human adipose tissue with a high proportion of oleic acid (18:1). In total, the morphological and chemical findings demonstrated that the yellow discoloration of the victims' clothes was caused by fat from traumatized adipose tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase α1 subunit.

PubMed

Zhou, Xihong; Chen, Jingqing; Chen, Jin; Wu, Weiche; Wang, Xinxia; Wang, Yizhen

2015-12-01

The current study was conducted to determine whether betaine could improve fatty acid oxidation, mitochondrial function and N6-methyladenosine (m(6)A) mRNA methylation in adipose tissue in high-fat-induced mice and how AMP-activated protein kinase α1 subunit (AMPKα1) was involved. AMPKα1 knockout mice and wild-type mice were fed either a low-fat diet, high-fat diet or high-fat diet supplemented with betaine in the drinking water for 8weeks. Our results showed that mitochondrial genes (PGC1α) and β-oxidation-related genes (CPT1a) at protein level were increased in wild-type mice supplemented with betaine when compared with those in mice with high-fat diet. Betaine also decreased FTO expression and improved m(6)A methylation in adipose tissue of wild-type mice with high-fat diet. However, betaine failed to exert the abovementioned effects in AMPKα1 knockout mice. In adipocytes isolated from mice with high-fat diet, betaine treatment increased lipolysis and lipid oxidation. Moreover, betaine decreased FTO expression and increased m(6)A methylation. However, while AMPKα1 was knockdown, no remarkable changes in adipocytes were observed under betaine treatment. Our results indicated that betaine supplementation rectified mRNA hypomethylation and high FTO expression induced by high-fat diet, which may contribute to its beneficial effects on impaired adipose tissue function. Our results suggested that the AMPKα1 subunit is required for the beneficial effects of betaine on dysfunctional adipose tissue and m(6)A methylation. These results may provide the foundation for a mechanism that links m(6)A methylation status in RNA, AMPKα1 phosphorylation and dysfunctional adipose tissue induced by high-fat diet. Copyright © 2015 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 ...

The sexual dimorphism of obesity

PubMed Central

Palmer, Biff F.; Clegg, Deborah J.

2015-01-01

The NIH has recently highlighted the importance of sexual dimorphisms and has mandated inclusion of both sexes in clinical trials and basic research. In this review we highlight new and novel ways sex hormones influence body adiposity and the metabolic syndrome. Understanding how and why metabolic processes differ by sex will enable clinicians to target and personalize therapies based on gender. Adipose tissue function and deposition differ by sex. Females differ with respect to distribution of adipose tissues, males tend to accrue more visceral fat, leading to the classic android body shape which has been highly correlated to increased cardiovascular risk; whereas females accrue more fat in the subcutaneous depot prior to menopause, a feature which affords protection from the negative consequences associated with obesity and the metabolic syndrome. After menopause, fat deposition and accrual shift to favor the visceral depot. This shift is accompanied by a parallel increase in metabolic risk reminiscent to that seen in men. A full understanding of the physiology behind why, and by what mechanisms, adipose tissues accumulate in specific depots and how these depots differ metabolically by sex is important in efforts of prevention of obesity and chronic disease. Estrogens, directly or through activation of their receptors on adipocytes and in adipose tissues, facilitate adipose tissue deposition and function. Evidence suggests that estrogens augment the sympathetic tone differentially to the adipose tissue depots favoring lipid accumulation in the subcutaneous depot in women and visceral fat deposition in men. At the level of adipocyte function, estrogens and their receptors influence the expandability of fat cells enhancing the expandability in the subcutaneous depot and inhibiting it in the visceral depot. Sex hormones clearly influence adipose tissue function and deposition, determining how to capture and utilize their function in a time of caloric surfeit, requires more information. The key will be harnessing the beneficial effects of sex hormones in such a way as to provide ‘healthy’ adiposity. PMID:25578600

Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

USDA-ARS?s Scientific Manuscript database

We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

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.

Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice.

PubMed

Zhang, C; McFarlane, C; Lokireddy, S; Masuda, S; Ge, X; Gluckman, P D; Sharma, M; Kambadur, R

2012-01-01

Although myostatin-null (Mstn (-/-)) mice fail to accumulate fat in adipose tissue when fed a high-fat diet (HFD), little is known about the molecular mechanism(s) behind this phenomenon. We therefore sought to identify the signalling pathways through which myostatin regulates accumulation and/or utilisation of fat. Wild-type, Mstn (-/-) and wild-type mice treated with soluble activin type IIB receptor (sActRIIB) were fed a control chow diet or an HFD for 12 weeks. Changes in gene expression were measured by microarray and quantitative PCR. Histological changes in white adipose tissue were assessed together with peripheral tissue fatty acid oxidation and changes in circulating hormones following HFD feeding. Our results demonstrate that inactivation of myostatin results in reduced fat accumulation in mice on an HFD. Molecular analysis revealed that metabolic benefits, due to lack of myostatin, are mediated through at least two independent mechanisms. First, lack of myostatin increased fatty acid oxidation in peripheral tissues through induction of enzymes involved in lipolysis and in fatty acid oxidation in mitochondria. Second, inactivation of myostatin also enhanced brown adipose formation in white adipose tissue of Mstn (-/-) mice. Consistent with the above, treatment of HFD-fed wild-type mice with the myostatin antagonist, sActRIIB, reduced the obesity phenotype. We conclude that absence of myostatin results in enhanced peripheral tissue fatty acid oxidation and increased thermogenesis, culminating in increased fat utilisation and reduced adipose tissue mass. Taken together, our data suggest that anti-myostatin therapeutics could be beneficial in alleviating obesity.

Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue1

PubMed Central

Lumeng, Carey N.; Liu, Jianhua; Geletka, Lynn; Delaney, Colin; DelProposto, Jennifer; Desai, Anjali; Oatmen, Kelsie; Martinez-Santibanez, Gabriel; Julius, Annabelle; Garg, Sanjay; Yung, Raymond L.

2011-01-01

Age-related adiposity has been linked to chronic inflammatory diseases in late-life. To date, the studies on adipose tissue leukocytes and aging have not taken into account the heterogeneity of adipose tissue macrophages (ATMs), nor have they examined how age impacts other leukocytes such as T cell in fat. Therefore, we have performed a detailed examination of ATM subtypes in young and old mice using state of the art techniques. Our results demonstrate qualitative changes in ATMs with aging that generate a decrease in resident Type 2 (M2) ATMs. The profile of ATMs in old fat shifts towards a pro-inflammatory environment with increased numbers of CD206-CD11c- (double negative) ATMs. The mechanism of this aging-induced shift in the phenotypic profile of ATMs was found to be related to a decrease in PPARγ expression in ATMs and alterations in chemokine/chemokine receptor expression profiles. Furthermore, we have revealed a profound and unexpected expansion of adipose tissue T (ATT) cells in visceral fat with aging that includes a significant induction of regulatory T cells (Tregs) in fat. Our findings demonstrate a unique inflammatory cell signature in the physiologic context of aging adipose tissue that differs from those induced in setting of diet-induced obesity. PMID:22075699

Free Fatty Acid Storage in Human Visceral and Subcutaneous Adipose Tissue

PubMed Central

Ali, Asem H.; Koutsari, Christina; Mundi, Manpreet; Stegall, Mark D.; Heimbach, Julie K.; Taler, Sandra J.; Nygren, Jonas; Thorell, Anders; Bogachus, Lindsey D.; Turcotte, Lorraine P.; Bernlohr, David; Jensen, Michael D.

2011-01-01

OBJECTIVE Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat. RESEARCH DESIGN AND METHODS Elective surgery patients received a bolus of [1-14C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured. RESULTS Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 μmol ⋅ kg adipose lipid−1 ⋅ min−1, P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P < 0.001), and both were greater in women than men (P < 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity. CONCLUSIONS Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation. PMID:21810594

Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice.

PubMed

Kobayashi, Shinjiro; Kawasaki, Yuki; Takahashi, Tatsuo; Maeno, Hironori; Nomura, Masaaki

2017-01-01

The Kampo medicine bofutsushosan (BTS; Pulvis ledebouriellae compositae ; Fang Feng Tong Sheng San ) has been used as an anti-obesity treatment in overweight patients. In this study, we assessed the underlying physiological changes induced by BTS in obese mice maintained on a high-fat diet. Male ICR mice were fed a 60% kcal fat diet for 5 weeks starting at 4 weeks of age and then fed the same diet with administration of water (control) or aqueous BTS extract (1.0-2.0 g/kg) for 25 days. Body weight, wet weight of isolated white adipose tissue, and obesity-related serum parameters (glucose, lipids, leptin, adiponectin) were measured after treatment. The mRNA expression levels of leptin, adiponectin, and UCP1 in the adipose tissues were determined by quantitative real-time polymerase chain reaction after the first 5 days of treatment. Bofutsushosan (1.5-2.0 g/kg) significantly decreased total body weight and total wet weight of white adipose tissue isolated from subcutaneous (retroperitoneal) and visceral regions (epididymal, mesenteric, and perirenal). At 2.0 g/kg, BTS also decreased total fat mass, visceral fat mass, and ratio of fat mass to body weight as measured by computed tomography, and significantly decreased epididymal adipocyte size after 14 and 25 days' treatment. Twenty-five days' treatment lowered serum glucose, insulin, leptin, and triglycerides, and reduced homeostasis model assessment-insulin resistance. Alternatively, 2.0 g/kg BTS significantly increased mRNA levels of adiponectin, leptin, and UCP1 in interscapular brown adipose tissue but not epididymal white adipose tissue after 5 days' administration. In the early administration period, BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues. With longer administration, BTS improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue volume and adipocyte size.

Eicosapentaenoic acid regulates brown adipose tissue gene expression and metabolism in high fat fed mice

USDA-ARS?s Scientific Manuscript database

Brown adipose tissue (BAT) is a thermogenic tissue, a key regulator of energy balance and a potential therapeutic target for obesity. We previously reported that eicosapentaenoic acid (EPA) reduced high fat (HF) diet-induced obesity and insulin resistance in mice, independent of energy intake. We hy...

Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

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

Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Ma, Shuai

Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressionsmore » of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.« less

Adipose-Derived Stem Cell Delivery for Adipose Tissue Engineering: Current Status and Potential Applications in a Tissue Engineering Chamber Model.

PubMed

Zhan, Weiqing; Tan, Shaun S; Lu, Feng

2016-08-01

In reconstructive surgery, there is a clinical need for adequate implants to repair soft tissue defects caused by traumatic injury, tumor resection, or congenital abnormalities. Adipose tissue engineering may provide answers to this increasing demand. This study comprehensively reviews current approaches to adipose tissue engineering, detailing different cell carriers under investigation, with a special focus on the application of adipose-derived stem cells (ASCs). ASCs act as building blocks for new tissue growth and as modulators of the host response. Recent studies have also demonstrated that the implantation of a hollow protected chamber, combined with a vascular pedicle within the fat flaps provides blood supply and enables the growth of large-volume of engineered soft tissue. Conceptually, it would be of value to co-regulate this unique chamber model with adipose-derived stem cells to obtain a greater volume of soft tissue constructs for clinical use. Our review provides a cogent update on these advances and details the generation of possible fat substitutes.

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.

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.

Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats

PubMed Central

Wu, Chunyan; Hwang, Su Hyeon; Jia, Yaoyao; Choi, Joobong; Kim, Yeon-Ji; Choi, Dahee; Pathiraja, Duleepa; Choi, In-Geol; Koo, Seung-Hoi

2017-01-01

Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats. After 6 weeks of administration, mice fed a high-fat diet (HFD) exhibited a marked reduction in adiposity. AzA treatment induced expression of PPAR-α and genes required for FAO in the liver and induced the expression of PPAR-γ coactivator 1-α (Ppargc1a) and uncoupling protein-1 (Ucp1) genes in brown adipose tissue (BAT). Moreover, treatment with AzA increased insulin sensitivity and ketone body levels. This led to a reduction in the respiratory quotient and an increase in the FAO rate, as indicated by indirect calorimetry. AzA treatment had similar antiobesogenic effects in HFD-fed ob/ob mice. Importantly, AzA-associated metabolic changes were completely abrogated in HFD-fed Olfr544–/– mice. To our knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting the fuel preference to fats in the liver and BAT. PMID:28990936

Effects of heat stress and insulin sensitizers on pig adipose tissue

USDA-ARS?s Scientific Manuscript database

Heat stress (HS) negatively impacts several swine production variables, including carcass fat quality. Pigs reared in HS have more adipose tissue than energetically predicted, explainable by HS-induced hyperinsulinemia. Study objectives were to evaluate insulin’s role in altering fat characteristics...

Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

PubMed Central

Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

2015-01-01

Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

PubMed

Foster, Michelle T; Shi, Haifei; Seeley, Randy J; Woods, Stephen C

2011-10-24

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. Published by Elsevier Inc.

Removal of Intra-abdominal Visceral Adipose Tissue Improves Glucose Tolerance in Rats: Role of Hepatic Triglyceride Storage

PubMed Central

Foster, Michelle T.; Shi, Haifei; Seeley, Randy J.; Woods, Stephen C.

2011-01-01

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. PMID:21683727

Control of brown and beige fat development

PubMed Central

Wang, Wenshan; Seale, Patrick

2017-01-01

Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli — notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells and revealed unanticipated cell-lineage relationships between vascular smooth muscle and beige adipocytes, and between brown fat and skeletal muscle cells. Additionally, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells play crucial roles in regulating the differentiation and function of brown and beige fat. PMID:27552974

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

PubMed

Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues, this review addresses the originality of the BMAT with regard to its development, anatomy, metabolic properties, and response to physiological cues.

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

PubMed Central

Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone–fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues – subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT – is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues, this review addresses the originality of the BMAT with regard to its development, anatomy, metabolic properties, and response to physiological cues. PMID:27445987

Female Nur77-Deficient Mice Show Increased Susceptibility to Diet-Induced Obesity

PubMed Central

Perez-Sieira, Sonia; Martinez, Gloria; Porteiro, Begoña; Lopez, Miguel; Vidal, Anxo; Nogueiras, Ruben; Dieguez, Carlos

2013-01-01

Adipose tissue is essential in the regulation of body weight. The key process in fat catabolism and the provision of energy substrate during times of nutrient deprivation or enhanced energy demand is the hydrolysis of triglycerides and the release of fatty acids and glycerol. Nur77 is a member of the NR4A subfamily of nuclear receptors that plays an important metabolic role, modulating hepatic glucose metabolism and lipolysis in muscle. However, its endogenous role on white adipose tissue, as well as the gender dependency of these mechanisms, remains largely unknown. Male and female wild type and Nur77 deficient mice were fed with a high fat diet (45% calories from fat) for 4 months. Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. Female, but not male Nur77 deficient mice, gained more weight and fat mass when compared to wild type mice fed with high fat diet, which can be explained by decreased energy expenditure. The lack of Nur77 also led to a decreased pHSL/HSL ratio in white adipose tissue and increased expression of CIDEA in brown adipose tissue of female Nur77 deficient mice. Overall, these findings suggest that Nur77 is an important physiological modulator of lipid metabolism in adipose tissue and that there are gender differences in the sensitivity to deletion of the Nur77 signaling. The decreased energy expenditure and the actions of Nur77 on liver, muscle, brown and white adipose tissue contribute to the increased susceptibility to diet-induced obesity in females lacking Nur77. PMID:23342015

Diet-induced thermogenesis is lower in rats fed a lard diet than in those fed a high oleic acid safflower oil diet, a safflower oil diet or a linseed oil diet.

PubMed

Takeuchi, H; Matsuo, T; Tokuyama, K; Shimomura, Y; Suzuki, M

1995-04-01

The objectives of the present study were to examine the effects of dietary fats differing in fatty acid composition on diet-induced thermogenesis, sympathetic activity in brown adipose tissue and body fat accumulation in rats. Rats were meal-fed for 12 wk an isoenergetic diet based on lard, high oleic acid safflower oil, safflower oil or linseed oil, and norepinephrine turnover rates in brown adipose tissue were then estimated. Whole-body oxygen consumption after the meal indicated that diet-induced thermogenesis was significantly lower in rats fed the lard diet than in those fed the other diets. The norepinephrine turnover rate in the interscapular brown adipose tissue was also significantly lower in the lard diet group than in the other diet groups. The carcass fat content was significantly higher in the lard diet group than in the other diet groups, whereas the abdominal adipose tissue weights were the same in all diet groups. These results suggest that the intake of animal fats rich in saturated fatty acids, compared with the intake of vegetable oils rich in monounsaturated or polyunsaturated fatty acids, decreases diet-induced thermogenesis by a decline of sympathetic activity in brown adipose tissue, resulting in the promotion of body fat accumulation.

Altered autophagy in human adipose tissues in obesity

USDA-ARS?s Scientific Manuscript database

Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

[Rosuvastatin improves insulin sensitivity in overweight rats induced by high fat diet. Role of SIRT1 in adipose tissue].

PubMed

Valero-Muñoz, María; Martín-Fernández, Beatriz; Ballesteros, Sandra; Cachofeiro, Victoria; Lahera, Vicente; de Las Heras, Natalia

2014-01-01

To study the effects of rosuvastatin on insulin resistance in overweight rats induced by high fat diet, as well as potential mediators. We used male Wistar rats fed with a standard diet (CT) or high fat diet (33.5% fat) (HFD); half of the animals HFD were treated with rosuvastatin (15mg/kg/day) (HFD+Rosu) for 7 weeks. HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Treatment with Rosu did not modify body weight or the weight of the adipose packages in HFD rat. Plasma glucose and insulin levels and HOMA index were higher in HFD rats, and rosuvastatin treatment reduced them. Leptin/adiponectin ratio in plasma and lumbar adipose tissue were higher in HDF rats, and were reduced by rosuvastatin. SIRT-1, PPAR-γ and GLUT-4 protein expression in lumbar adipose tissue were lower in HFD rats and Rosu normalized expression of the three mediators. Rosuvastatin ameliorates insulin sensitivity induced by HFD in rats. This effect is mediated by several mechanisms including reduction of leptin and enhancement of SIRT-1, PPAR-γ and GLUT-4 expression in white adipose tissue. SIRT1 could be considered a major mediator of the beneficial effects of rosuvastatin on insulin sensitivity in overweight rats induced by diet. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins

PubMed Central

Santosa, Sylvia; Jensen, Michael D.

2012-01-01

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [3H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-13C]palmitate and [1-14C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans. PMID:22363653

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.

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

PubMed

Escobedo, Noelia; Oliver, Guillermo

2017-10-03

Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

Noncanonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion.

PubMed

Fuster, José J; Zuriaga, María A; Ngo, Doan Thi-Minh; Farb, Melissa G; Aprahamian, Tamar; Yamaguchi, Terry P; Gokce, Noyan; Walsh, Kenneth

2015-04-01

Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Relationship between visceral obesity and plasma fibrinogen in obese children.

PubMed

Hafez, Mona; El-Masry, Sahar; Musa, Noha; Fathy, Marwa; Hassan, Mona; Hassan, Nayera; El Husseiny, Mohamed; Tareef, Mahmoud

2016-03-01

The prevalence of obesity in children and adolescents has increased significantly worldwide with an alarming rise of its co-morbidities. The excess of visceral adipose tissue is associated with hypertension, prothrombotic and pro-inflammatory states. Our aim was to find a possible association between visceral obesity and plasma fibrinogen, as one of the cardiovascular risk factors, in obese children. Forty-three obese children and 40 non-obese controls were studied regarding their history, complete physical examination, anthropometric assessment, body composition analysis, ultrasonographic measurement of visceral adipose tissue and subcutaneous fat as well as laboratory measurement of plasma fibrinogen. Our study revealed significant higher levels of fibrinogen in obese children than controls (14.5+5.1 and 2.9+0.52 mg/mL, respectively) with p-value <0.01. Moreover, the obese group had statistically significant difference in visceral fat (5.96+0.77 cm) and subcutaneous fat (2.66+0.70 cm) than controls (2.45+0.65 and 0.70+0.18 mg/mL, respectively) with p-value <0.01. In addition, fibrinogen had significant positive correlation with body mass index (r=0.327), waist/hip ratio (r=0.394), fat percentage (r=0.301), visceral adipose tissue (r=0.323) and subcutaneous fat (r=0.301). There was highly significant increase in the fibrinogen level, visceral and subcutaneous abdominal fat in the obese group with insignificant sex differences. Fibrinogen had a significant positive correlation with the different adiposity markers, blood pressure, visceral and subcutaneous fat. Visceral adipose tissue is a stronger predictor for cardiovascular risk compared to subcutaneous fat.

Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

PubMed

Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-Ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

2016-03-01

Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

Central Effects of Estradiol in the Regulation of Adiposity

PubMed Central

Brown, LM; Clegg, DJ

2010-01-01

In recent years, obesity and its associated health disorders and costs have increased. Accumulation of adipose tissue, or fat, in the intra-abdominal adipose depot is associated with an increased risk of developing cardiovascular problems, type-2 diabetes mellitus, certain cancers, and other disorders like the metabolic syndrome. Males and females differ in terms of how and where their body fat is stored, in their hormonal secretions, and in their neural responses to signals regulating weight and body fat distribution. Men and post-menopausal women accumulate more fat in their intra-abdominal depots than pre-menopausal women, resulting in a greater risk of developing complications associated with obesity. The goal of this review is to discuss the current literature on sexual dimorphisms in body weight regulation, adipose tissue accrual and deposition. PMID:20035866

[Human brown adipose tissue].

PubMed

Virtanen, Kirsi A; Nuutila, Pirjo

2015-01-01

Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues

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

Yamada, Tomoya, E-mail: toyamada@affrc.go.jp; Higuchi, Mikito; Nakanishi, Naoto

Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere lengthmore » of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. - Highlights: • Visceral adipose tissue express higher pref-1 mRNA than other anatomical sites. • Telomere length in visceral adipose tissue is longer than other anatomical sites. • Telomere length of adipose tissue is not associated with adipocyte size. • Pref-1 mRNA is negatively correlated with intramuscular and visceral adipocyte size.« less

Changes in visceral adipose tissue plasma membrane lipid composition in old rats are associated with adipocyte hypertrophy with aging.

PubMed

Bonzón-Kulichenko, Elena; Moltó, Eduardo; Pintado, Cristina; Fernández, Alejandro; Arribas, Carmen; Schwudke, Dominik; Gallardo, Nilda; Shevchenko, Andrej; Andrés, Antonio

2018-04-16

Increased adiposity, through adipocyte hypertrophy and/or hyperplasia, characterizes aging and obesity. Both are leptin-resistant states, associated to disturbed lipid metabolism, reduced insulin sensitivity and inflammation. Nevertheless, fat tissue dysfunction appears earlier in obesity than in normal aging. In contrast, lipodystrophy is accompanied by diabetes, and improving the fat cell capacity to expand rescues the diabetic phenotype. Fat tissue dysfunction is extensively studied in the diet-induced obesity, but remains relatively neglected in the aging-associated obesity. In the Wistar rat, as occurs in humans, early or middle aging is accompanied by an increase in adiposity. Using this experimental model, we describe the molecular mechanisms contributing to the white adipose tissue (WAT) hypertrophy. WAT from middle-old age rats is characterized by decreased basal lipogenesis and lipolysis, increased esterification, as demonstrated by the higher TAG and cholesterol content in visceral WAT, and the maintenance of total ceramide levels within normal values. In addition, we describe alterations in the adipose tissue plasma membrane lipid composition, as increased total ether-phosphatidylcholine, sphingomyelin and free cholesterol levels that favor an enlarged fat cell size with aging. All these metabolic changes may be regarded as a survival advantage that prevents the aged rats from becoming overtly diabetic.

Strategies for reducing body fat mass: effects of liposuction and exercise on cardiovascular risk factors and adiposity

PubMed Central

Benatti, Fabiana Braga; Lira, Fábio Santos; Oyama, Lila Missae; do Nascimento, Cláudia Maria da Penha Oller; Lancha, Antonio Herbert

2011-01-01

Liposuction is the most popular aesthetic surgery performed in Brazil and worldwide. Evidence showing that adipose tissue is a metabolically active tissue has led to the suggestion that liposuction could be a viable method for improving metabolic profile through the immediate loss of adipose tissue. However, the immediate liposuction-induced increase in the proportion of visceral to subcutaneous adipose tissue could be detrimental to metabolism, because a high proportion of visceral to subcutaneous adipose tissue is associated with risk factors for cardiovascular disease. The results of studies investigating the effects of liposuction on the metabolic profile are inconsistent, however, with most studies reporting either no change or improvements in one or more cardiovascular risk factors. In addition, animal studies have demonstrated a compensatory growth of intact adipose tissue in response to lipectomy, although studies with humans have reported inconsistent results. Exercise training improves insulin sensitivity, inflammatory balance, lipid oxidation, and adipose tissue distribution; increases or preserves the fat-free mass; and increases total energy expenditure. Thus, liposuction and exercise appear to directly affect metabolism in similar ways, which suggests a possible interaction between these two strategies. To our knowledge, no studies have reported the associated effects of liposuction and exercise in humans. Nonetheless, one could suggest that exercise training associated with liposuction could attenuate or even block the possible compensatory fat deposition in intact depots or regrowth of the fat mass and exert an additive or even a synergistic effect to liposuction on improving insulin sensitivity and the inflammatory balance, resulting in an improvement of cardiovascular risk factors. Consequently, one could suggest that liposuction and exercise appear to be safe and effective strategies for either the treatment of metabolic disorders or aesthetic purposes. PMID:21779146

Exercise and caloric restriction alter the immune system of mice submitted to a high-fat diet.

PubMed

Wasinski, Frederick; Bacurau, Reury F P; Moraes, Milton R; Haro, Anderson S; Moraes-Vieira, Pedro M M; Estrela, Gabriel R; Paredes-Gamero, Edgar J; Barros, Carlos C; Almeida, Sandro S; Câmara, Niels O S; Araujo, Ronaldo C

2013-01-01

As the size of adipocytes increases during obesity, the establishment of resident immune cells in adipose tissue becomes an important source of proinflammatory mediators. Exercise and caloric restriction are two important, nonpharmacological tools against body mass increase. To date, their effects on the immune cells of adipose tissue in obese organisms, specifically when a high-fat diet is consumed, have been poorly investigated. Thus, after consuming a high-fat diet, mice were submitted to chronic swimming training or a 30% caloric restriction in order to investigate the effects of both interventions on resident immune cells in adipose tissue. These strategies were able to reduce body mass and resulted in changes in the number of resident immune cells in the adipose tissue and levels of cytokines/chemokines in serum. While exercise increased the number of NK cells in adipose tissue and serum levels of IL-6 and RANTES, caloric restriction increased the CD4+/CD8+ cell ratio and MCP-1 levels. Together, these data demonstrated that exercise and caloric restriction modulate resident immune cells in adipose tissues differently in spite of an equivalent body weight reduction. Additionally, the results also reinforce the idea that a combination of both strategies is better than either individually for combating obesity.

Dietary ribonucleic acid suppresses inflammation of adipose tissue and improves glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high-fat diet.

PubMed

Sakai, Tohru; Taki, Tomoyo; Nakamoto, Akiko; Tazaki, Shiho; Arakawa, Mai; Nakamoto, Mariko; Tsutsumi, Rie; Shuto, Emi

2015-01-01

Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold

PubMed Central

Kim, Eun Na; Sung, Myung Whun; Kwon, Tack-Kyun; Cho, Yong Woo; Kwon, Seong Keun

2016-01-01

Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps—ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest. PMID:27768757

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.

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...

Characterization of human brown adipose tissue by chemical-shift water-fat MRI.

PubMed

Hu, Houchun H; Perkins, Thomas G; Chia, Jonathan M; Gilsanz, Vicente

2013-01-01

The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

PubMed

Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

2015-01-01

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

Adipose tissue and inflammatory bowel disease pathogenesis.

PubMed

Fink, Christopher; Karagiannides, Iordanes; Bakirtzi, Kyriaki; Pothoulakis, Charalabos

2012-08-01

Creeping fat has long been recognized as an indicator of Crohn's disease (CD) activity. Although most patients with CD have normal or low body mass index (BMI), the ratio of intraabdominal fat to total abdominal fat is far greater than that of controls. The obesity epidemic has instructed us on the inflammatory nature of hypertrophic adipose tissue and similarities between mesenteric depots in obese and CD patients can be drawn. However, several important physiological differences exist between these two depots as well. While the molecular basis of the crosstalk between mesenteric adipose and the inflamed intestine in CD is largely unknown, novel evidence implicates neuropeptides along with adipocyte-derived paracrine mediators (adipokines) as potential targets for future investigations and highlight adipose tissue physiology as a potential important determinant in the course of IBD. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia.

PubMed

Ebadi, Maryam; Mazurak, Vera C

2015-01-01

Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

PubMed

Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

2018-04-01

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Adipocyte Origins: Weighing the Possibilities

PubMed Central

Majka, Susan M.; Barak, Yaacov; Klemm, Dwight J.

2012-01-01

Adipose tissue is the primary energy reservoir in the body and an important endocrine organ that plays roles in energy homeostasis, feeding, insulin sensitivity and inflammation. While it was tacitly assumed that fat in different anatomical locations had a common origin and homogenous function, it is now clear that regional differences exist in adipose tissue characteristics and function. This is exemplified by the link between increased deep abdominal or visceral fat, but not peripheral adipose tissue, and the metabolic disturbances associated with obesity. Regional differences in fat function are due in large part to distinct adipocyte populations that comprise the different fat depots. Evidence accrued primarily in the last decade indicate that the distinct adipocyte populations are generated by a number of processes during and after development. These include the production of adipocytes from different germ cell layers, the formation of distinct preadipocyte populations from mesenchymal progenitors of mesodermal origin, and the production of adipocytes from hematopoietic stem cells from the bone marrow. This review will examine each of these process and their relevance to normal adipose tissue formation and contribution to obesity-related diseases. PMID:21544899

Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

PubMed

Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

2017-06-15

Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

A mircroarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice

USDA-ARS?s Scientific Manuscript database

A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose...

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.

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue.

PubMed

Harford, Karen A; Reynolds, Clare M; McGillicuddy, Fiona C; Roche, Helen M

2011-11-01

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

The Beneficial Effect of Anthocyanidin-Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High-Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions.

PubMed

da Costa, Gisele França; Santos, Izabelle Barcellos; de Bem, Graziele Freitas; Cordeiro, Viviane Silva Cristino; da Costa, Cristiane Aguiar; de Carvalho, Lenize Costa Reis Marins; Ognibene, Dayane Teixeira; Resende, Angela Castro; de Moura, Roberto Soares

2017-10-01

We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF-fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Alpha-syntrophin deficient mice are protected from adipocyte hypertrophy and ectopic triglyceride deposition in obesity.

PubMed

Eisinger, Kristina; Rein-Fischboeck, Lisa; Neumeier, Markus; Schmidhofer, Sandra; Pohl, Rebekka; Haberl, Elisabeth M; Liebisch, Gerhard; Kopp, Andrea; Schmid, Andreas; Krautbauer, Sabrina; Buechler, Christa

2018-06-01

Alpha-syntrophin (SNTA) is a molecular adapter protein which is expressed in adipocytes. Knock-down of SNTA in 3T3-L1 preadipocytes increases cell proliferation, and differentiated adipocytes display small lipid droplets. These effects are both characteristics of healthy adipose tissue growth which is associated with metabolic improvements in obesity. To evaluate a role of SNTA in adipose tissue morphology and obesity associated metabolic dysfunction, SNTA deficient mice were fed a standard chow or a high fat diet. Mice deficient of SNTA had less fat mass and smaller adipocytes in obesity when compared to control animals. Accordingly, these animals did not develop liver steatosis and did not store excess triglycerides in skeletal muscle upon high fat diet feeding. SNTA-/- animals were protected from hyperinsulinemia and hepatic insulin resistance. Of note, body-weight, food uptake, and serum lipids were normal in the SNTA null mice. SNTA was induced in adipose tissues but not in the liver of diet induced obese and ob/ob mice. In human subcutaneous and visceral fat of seven patients SNTA was similarly expressed and was not associated with body mass index. Current data demonstrate beneficial effects of SNTA deficiency in obesity which is partly attributed to smaller adipocytes and reduced white adipose tissue mass. Higher SNTA protein in fat depots of obese mice may contribute to adipose tissue hypertrophy and ectopic lipid deposition which has to be confirmed in humans. Copyright © 2018 Elsevier Inc. All rights reserved.

Redox implications in adipose tissue (dys)function—A new look at old acquaintances

PubMed Central

Jankovic, Aleksandra; Korac, Aleksandra; Buzadzic, Biljana; Otasevic, Vesna; Stancic, Ana; Daiber, Andreas; Korac, Bato

2015-01-01

Obesity is an energy balance disorder associated with dyslipidemia, insulin resistance and diabetes type 2, also summarized with the term metabolic syndrome or syndrome X. Increasing evidence points to “adipocyte dysfunction”, rather than fat mass accretion per se, as the key pathophysiological factor for metabolic complications in obesity. The dysfunctional fat tissue in obesity characterizes a failure to safely store metabolic substrates into existing hypertrophied adipocytes and/or into new preadipocytes recruited for differentiation. In this review we briefly summarize the potential of redox imbalance in fat tissue as an instigator of adipocyte dysfunction in obesity. We reveal the challenge of the adipose redox changes, insights in the regulation of healthy expansion of adipose tissue and its reduction, leading to glucose and lipids overflow. PMID:26177468

Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots

PubMed Central

Chusyd, Daniella E.; Wang, Donghai; Huffman, Derek M.; Nagy, Tim R.

2016-01-01

The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue (WAT) development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of WAT. Thus, further research is warranted to more carefully define the strengths and limitations of rodent WAT as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat. PMID:27148535

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

PubMed

Almeida, Mariana M; Dias-Rocha, Camilla P; Souza, André S; Muros, Mariana F; Mendonca, Leonardo S; Pazos-Moura, Carmen C; Trevenzoli, Isis H

2017-11-01

Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

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

Postprandial fatty acid uptake and adipocyte remodeling in angiotensin type 2 receptor-deficient mice fed a high-fat/high-fructose diet

PubMed Central

Noll, Christophe; Labbé, Sébastien M.; Pinard, Sandra; Shum, Michael; Bilodeau, Lyne; Chouinard, Lucie; Phoenix, Serge; Lecomte, Roger; Carpentier, André C.; Gallo-Payet, Nicole

2016-01-01

ABSTRACT The role of the angiotensin type-2 receptor in adipose physiology remains controversial. The aim of the present study was to demonstrate whether genetic angiotensin type-2 receptor-deficiency prevents or worsens metabolic and adipose tissue morphometric changes observed following a 6-week high-fat/high-fructose diet with injection of a small dose of streptozotocin. We compared tissue uptake of nonesterified fatty acid and dietary fatty acid in wild-type and angiotensin type-2 receptor-deficient mice by using the radiotracer 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid in mice fed a standard or high-fat diet. Postprandial fatty acid uptake in the heart, liver, skeletal muscle, kidney and adipose tissue was increased in wild-type mice after a high-fat diet and in angiotensin type-2 receptor-deficient mice on both standard and high-fat diets. Compared to the wild-type mice, angiotensin type-2 receptor-deficient mice had a lower body weight, an increase in fasting blood glucose and a decrease in plasma insulin and leptin levels. Mice fed a high-fat diet exhibited increased adipocyte size that was prevented by angiotensin type-2 receptor-deficiency. Angiotensin type-2 receptor-deficiency abolished the early hypertrophic adipocyte remodeling induced by a high-fat diet. The small size of adipocytes in the angiotensin type-2 receptor-deficient mice reflects their inability to store lipids and explains the increase in fatty acid uptake in non-adipose tissues. In conclusion, a genetic deletion of the angiotensin type-2 receptor is associated with metabolic dysfunction of white adipose depots, and indicates that adipocyte remodeling occurs before the onset of insulin resistance in the high-fat fed mouse model. PMID:27144096

Why does starvation make bones fat?

PubMed Central

Devlin, Maureen J.

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. Here I review the possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? To evaluate these possibilities, here I review what is known about the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. PMID:21793093

Why does starvation make bones fat?

PubMed

Devlin, Maureen J

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. This review considers several possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? These possibilities are evaluated in terms of the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. Copyright © 2011 Wiley-Liss, Inc.

Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.

PubMed

Kuipers, Allison L; Zmuda, Joseph M; Carr, J Jeffrey; Terry, James G; Nair, Sangeeta; Cvejkus, Ryan; Bunker, Clareann H; Patrick, Alan L; Wassel, Christina L; Miljkovic, Iva

2017-08-01

There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body. Copyright © 2017 Elsevier B.V. All rights reserved.

FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial.

PubMed

Zhang, Xiaomin; Qi, Qibin; Zhang, Cuilin; Smith, Steven R; Hu, Frank B; Sacks, Frank M; Bray, George A; Qi, Lu

2012-11-01

Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902.

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.

Regulation of leptin synthesis in white adipose tissue of the female fruit bat, Cynopterus sphinx: role of melatonin with or without insulin.

PubMed

Banerjee, A; Udin, S; Krishna, A

2011-02-01

Factors regulating leptin synthesis during adipogenesis in wild species are not well known. Studies in the female Cynopterus sphinx bat have shown that it undergoes seasonal changes in its fat deposition and serum leptin and melatonin levels. The aim of the present study was to investigate the hormonal regulation of leptin synthesis by the white adipose tissue during the period of fat deposition in female C. sphinx. This study showed a significant correlation between the seasonal changes in serum melatonin level with the circulating leptin level (r = 0.78; P < 0.05) and with the changes in body fat mass (r = 0.88; P < 0.05) in C. sphinx. A significant correlation between circulating insulin and leptin levels (r = 0.65; P < 0.05) was also found in this species. This in vivo finding suggests that melatonin together with insulin may enhance leptin synthesis by increasing adipose tissue accumulation. The in vitro study showed that melatonin interacts synergistically with insulin in stimulating leptin synthesis by adipose tissue in C. sphinx. The study showed MT(2) receptors in adipose tissue and a stimulatory effect of melatonin on leptin synthesis, which was blocked by treatment with an MT(2) receptor antagonist, suggesting that the effect of melatonin on leptin synthesis by adipose tissue is mediated through the MT(2) receptor in C. sphinx. The in vitro study showed that the synthesis of leptin is directly proportional to the amount of glucose uptake by the adipose tissue. It further showed that melatonin together with insulin synergistically enhanced the leptin synthesis by adipose tissue through phosphorylation of mitogen-activated protein kinase in C. sphinx.

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

Does bariatric surgery improve adipose tissue function?

PubMed Central

Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

2017-01-01

Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity.

PubMed

Lee, Mi-Jeong; Pramyothin, Pornpoj; Karastergiou, Kalypso; Fried, Susan K

2014-03-01

Central obesity is associated with insulin resistance and dyslipidemia. Thus, the mechanisms that control fat distribution and its impact on systemic metabolism have importance for understanding the risk for diabetes and cardiovascular disease. Hypercortisolemia at the systemic (Cushing's syndrome) or local levels (due to adipose-specific overproduction via 11β-hydroxysteroid dehydrogenase 1) results in the preferential expansion of central, especially visceral fat depots. At the same time, peripheral subcutaneous depots can become depleted. The biochemical and molecular mechanisms underlying the depot-specific actions of glucocorticoids (GCs) on adipose tissue function remain poorly understood. GCs exert pleiotropic effects on adipocyte metabolic, endocrine and immune functions, and dampen adipose tissue inflammation. GCs also regulate multiple steps in the process of adipogenesis. Acting synergistically with insulin, GCs increase the expression of numerous genes involved in fat deposition. Variable effects of GC on lipolysis are reported, and GC can improve or impair insulin action depending on the experimental conditions. Thus, the net effect of GC on fat storage appears to depend on the physiologic context. The preferential effects of GC on visceral adipose tissue have been linked to higher cortisol production and glucocorticoid receptor expression, but the molecular details of the depot-dependent actions of GCs are only beginning to be understood. In addition, increasing evidence underlines the importance of circadian variations in GCs in relationship to the timing of meals for determining their anabolic actions on the adipocyte. In summary, although the molecular mechanisms remain to be fully elucidated, there is increasing evidence that GCs have multiple, depot-dependent effects on adipocyte gene expression and metabolism that promote central fat deposition. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

PubMed

Guo, Tingqing; Jou, William; Chanturiya, Tatyana; Portas, Jennifer; Gavrilova, Oksana; McPherron, Alexandra C

2009-01-01

Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/-) mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/-) mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/-) mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/-) mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/-) mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/-) mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

The Great Roundleaf Bat (Hipposideros armiger) as a Good Model for Cold-Induced Browning of Intra-Abdominal White Adipose Tissue

PubMed Central

Ke, Shanshan; Fang, Na; Irwin, David M.; Lei, Ming; Zhang, Junpeng; Shi, Huizhen; Zhang, Shuyi; Wang, Zhe

2014-01-01

Background Inducing beige fat from white adipose tissue (WAT) is considered to be a shortcut to weight loss and increasingly becoming a key area in research into treatments for obesity and related diseases. However, currently, animal models of beige fat are restricted to rodents, where subcutaneous adipose tissue (sWAT, benign WAT) is more liable to develop into the beige fat under specific activators than the intra-abdominal adipose tissue (aWAT, malignant WAT) that is the major source of obesity related diseases in humans. Methods Here we induced beige fat by cold exposure in two species of bats, the great roundleaf bat (Hipposideros armiger) and the rickett's big-footed bat (Myotis ricketti), and compared the molecular and morphological changes with those seen in the mouse. Expression of thermogenic genes (Ucp1 and Pgc1a) was measured by RT-qPCR and adipocyte morphology examined by HE staining at three adipose locations, sWAT, aWAT and iBAT (interscapular brown adipose tissue). Results Expression of Ucp1 and Pgc1a was significantly upregulated, by 729 and 23 fold, respectively, in aWAT of the great roundleaf bat after exposure to 10°C for 7 days. Adipocyte diameters of WATs became significantly reduced and the white adipocytes became brown-like in morphology. In mice, similar changes were found in the sWAT, but much lower amounts of changes in aWAT were seen. Interestingly, the rickett's big-footed bat did not show such a tendency in beige fat. Conclusions The great roundleaf bat is potentially a good animal model for human aWAT browning research. Combined with rodent models, this model should be helpful for finding therapies for reducing harmful aWAT in humans. PMID:25393240

Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

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

Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp; Liu, Jun-Qian; Ohta, Ken-ichi

Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved bymore » separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.« less

Outcome of Conventional Adipose Tissue Grafting for Contour Deformities of Face and Role of Ex Vivo Expanded Adipose Tissue-Derived Stem Cells in Treatment of Such Deformities.

PubMed

Bashir, Muhammad Mustehsan; Sohail, Muhammad; Bashir, Afzaal; Khan, Farid Ahmad; Jan, Sadia Nosheen; Imran, Muhammad; Ahmad, Fridoon Jawad; Choudhery, Mahmood S

2018-02-23

To evaluate the outcomes of conventional fat grafting for facial contour deformities and to describe clinical outcome of a patient with contour deformity of face treated with ex vivo expanded adipose tissue-derived mesenchymal stem cells (ASCs) enriched fat graft. The Department of Plastic Surgery and Tissue Engineering and Regenerative Medicine Laboratory, King Edward Medical University/Mayo Hospital, Lahore, from September 2015 to September 2017. Patients with contour deformities of face requiring soft tissue augmentation were included. Fat was harvested, processed, and injected following a standard protocol. Both subjective and objective assessments were performed and complications were also noted. Twenty-five patients underwent 51 fat-grafting sessions over a period of 24 months. Eighteen (72%) patients underwent multiple fat-grafting sessions. Mean (standard deviation) soft tissue thickness after 72 hours and 6 months of first fat graft session was 18.62 (7.2) and 12.88 (6.21) mm, respectively, which corresponds to 30.77 (13)% reduction of transplanted fat. Physician and patient assessment scores were 3.42 (0.92) and 4 (1.04), respectively. Few minor complications were observed. In the patient undergoing ex vivo expanded ASCs enriched fat graft, there was minimal decrease in soft tissue thickness of treated area (44 mm vs 42 mm) 6 months postoperatively and patient was highly satisfied with the outcome after the single session. Conventional fat grafting is safe for correction of facial contour deformities. However, procedure needs to be repeated multiple times to produce satisfactory results. Beneficial effects of ex vivo expanded ASCs enriched fat grafting have a potential to alter the current treatment paradigm of fat grafting for soft tissue reconstruction.

Coordinated improvement in glucose tolerance, liver steatosis and obesity-associated inflammation by cannabinoid 1 receptor antagonism in fat Aussie mice.

PubMed

Bell-Anderson, K S; Aouad, L; Williams, H; Sanz, F R; Phuyal, J; Larter, C Z; Farrell, G C; Caterson, I D

2011-12-01

Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR141716 in foz/foz mice. Male wildtype (WT) and foz/foz mice were fed a chow or high-fat diet (45% saturated fat). Vehicle or SR141716 (10 mg kg(-1) per day) was administered in jelly once daily for 4 weeks from 4 months of age. Foz/foz mice were obese but had less epididymal adipose tissue mass than fat-fed WT mice despite being significantly heavier. Liver weight was increased by twofold in foz/foz compared with WT mice and showed significant steatogenesis associated with impaired liver function. Foz/foz and fat-fed WT mice were glucose intolerant as determined by oral glucose tolerance test. In chow-fed foz/foz mice, SR141716 reduced body weight, liver weight, reversed hepatosteatosis and glucose intolerance. Subcutaneous white adipose tissue gene expression of the macrophage-specific marker Cd68 reflected the improvements in the metabolic status by SR141716 in these mice. The results are consistent with the hypothesis that foz/foz mice have defective lipid metabolism, are unable to adequately store fat in adipose tissue but instead sequester fat ectopically in other metabolic tissues (liver) leading to insulin resistance and hepatic steatosis associated with inflammation. Our findings suggest that SR141716 can improve liver lipid metabolism in foz/foz mice in line with improved insulin sensitivity and adipose tissue inflammation.

Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells.

PubMed

Kuan, Emma L; Ivanov, Stoyan; Bridenbaugh, Eric A; Victora, Gabriel; Wang, Wei; Childs, Ed W; Platt, Andrew M; Jakubzick, Claudia V; Mason, Robert J; Gashev, Anatoliy A; Nussenzweig, Michel; Swartz, Melody A; Dustin, Michael L; Zawieja, David C; Randolph, Gwendalyn J

2015-06-01

Collecting lymphatic vessels (CLVs), surrounded by fat and endowed with contractile muscle and valves, transport lymph from tissues after it is absorbed into lymphatic capillaries. CLVs are not known to participate in immune responses. In this study, we observed that the inherent permeability of CLVs allowed broad distribution of lymph components within surrounding fat for uptake by adjacent macrophages and dendritic cells (DCs) that actively interacted with CLVs. Endocytosis of lymph-derived Ags by these cells supported recall T cell responses in the fat and also generated Ag-bearing DCs for emigration into adjacent lymph nodes (LNs). Enhanced recruitment of DCs to inflammation-reactive LNs significantly relied on adipose tissue DCs to maintain sufficient numbers of Ag-bearing DCs as the LN expanded. Thus, CLVs coordinate inflammation and immunity within adipose depots and foster the generation of an unexpected pool of APCs for Ag transport into the adjacent LN. Copyright © 2015 by The American Association of Immunologists, Inc.

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

PubMed

Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

PubMed Central

Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

2013-01-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals. PMID:23213032

Vitamin D deficiency decreases adiposity in rats and causes altered expression of uncoupling proteins and steroid receptor coactivator3.

PubMed

Bhat, Mehrajuddin; Noolu, Bindu; Qadri, Syed S Y H; Ismail, Ayesha

2014-10-01

The vitamin D endocrine system is functional in the adipose tissue, as demonstrated in vitro, in cultured adipocytes, and in vivo in mutant mice that developed altered lipid metabolism and fat storage in the absence of either 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or the vitamin D receptor. The aim of the present study was to examine the role of vitamin D and calcium on body adiposity in a diet-induced vitamin D deficient rat model. Vitamin D-deficient rats gained less weight and had lower amounts of visceral fat. Consistent with reduced adipose tissue mass, the vitamin D-deficient rats had low circulating levels of leptin, which reflects body fat stores. Expression of vitamin D and calcium sensing receptors, and that of genes involved in adipogenesis such as peroxisome proliferator-activated receptor, fatty acid synthase and leptin were significantly reduced in white adipose tissue of deficient rats compared to vitamin D-sufficient rats. Furthermore, the expression of uncoupling proteins (Ucp1 and Ucp2) was elevated in the white adipose tissue of the deficient rat indicative of higher energy expenditure, thereby leading to a lean phenotype. Expression of the p160 steroid receptor coactivator3 (SRC3), a key regulator of adipogenesis in white adipose tissue was decreased in vitamin D-deficient state. Interestingly, most of the changes observed in vitamin D deficient rats were corrected by calcium supplementation alone. Our data demonstrates that dietary vitamin D and calcium regulate adipose tissue function and metabolism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue.

PubMed

Yu, Xiao; Tang, Yuhan; Liu, Peiyi; Xiao, Lin; Liu, Liegang; Shen, Ruiling; Deng, Qianchun; Yao, Ping

2017-11-08

Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.

Flow cytometry on the stromal-vascular fraction of white adipose tissue.

PubMed

Brake, Danett K; Smith, C Wayne

2008-01-01

Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow cytometry to analyze cell surface markers on leukocytes. Here, we present a technical approach to identify subsets of leukocytes that differentially express cell surface markers.

Influence of adipocyte size and adipose depot on the in vitro lipolytic activity and insulin sensitivity of adipose tissue in dairy cows at the end of the dry period.

PubMed

De Koster, J; Van den Broeck, W; Hulpio, L; Claeys, E; Van Eetvelde, M; Hermans, K; Hostens, M; Fievez, V; Opsomer, G

2016-03-01

The aim of the present research was to describe characteristics of adipose tissue lipolysis in dairy cows with a variable body condition score (BCS). Ten clinically healthy Holstein Friesian cows were selected based on BCS and euthanized 10 to 13 d before the expected parturition date. Immediately after euthanasia, adipose tissue samples were collected from subcutaneous and omental fat depots. In both depots, we observed an increase in adipocyte size with increasing BCS. Using an in vitro explant culture of subcutaneous and omental adipose tissue, we aimed to determine the influence of adipocyte size and localization of adipose depot on the lipolytic activity in basal conditions and after addition of isoproterenol (nonselective β-agonist) and insulin in different concentrations. Glycerol release in the medium was used as a measure for lipolytic activity. We observed that the basal lipolytic activity of subcutaneous and omental adipose tissue increased with adipocyte volume, meaning that larger fat cells have higher basal lipolytic activity independent of the location of the adipose depot. Dose-response curves were created between the concentration of isoproterenol or insulin and the amount of glycerol released. The shape of the dose-response curves is determined by the concentration of isoproterenol and insulin needed to elicit the half-maximal effect and the maximal amount of stimulated glycerol release or the maximal inhibitory effect of insulin. We observed that larger fat cells released more glycerol upon maximal stimulation with isoproterenol and this was more pronounced in subcutaneous adipose tissue. Additionally, larger fat cells had a higher sensitivity toward lipolytic signals. We observed a trend for larger adipocytes to be more resistant to the maximal antilipolytic effect of insulin. The insulin concentration needed to elicit the half-maximal inhibitory effect of insulin was within the physiological range of insulin and was not influenced by adipocyte size or adipose depot. We conclude that overconditioned cows have larger adipocytes and are predisposed to excessive mobilization of body fat due to a higher basal and stimulated lipolytic activity of large adipocytes while the antilipolytic effect of insulin is preserved. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Unsupervised quantification of abdominal fat from CT images using Greedy Snakes

NASA Astrophysics Data System (ADS)

Agarwal, Chirag; Dallal, Ahmed H.; Arbabshirani, Mohammad R.; Patel, Aalpen; Moore, Gregory

2017-02-01

Adipose tissue has been associated with adverse consequences of obesity. Total adipose tissue (TAT) is divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Intra-abdominal fat (VAT), located inside the abdominal cavity, is a major factor for the classic obesity related pathologies. Since direct measurement of visceral and subcutaneous fat is not trivial, substitute metrics like waist circumference (WC) and body mass index (BMI) are used in clinical settings to quantify obesity. Abdominal fat can be assessed effectively using CT or MRI, but manual fat segmentation is rather subjective and time-consuming. Hence, an automatic and accurate quantification tool for abdominal fat is needed. The goal of this study is to extract TAT, VAT and SAT fat from abdominal CT in a fully automated unsupervised fashion using energy minimization techniques. We applied a four step framework consisting of 1) initial body contour estimation, 2) approximation of the body contour, 3) estimation of inner abdominal contour using Greedy Snakes algorithm, and 4) voting, to segment the subcutaneous and visceral fat. We validated our algorithm on 952 clinical abdominal CT images (from 476 patients with a very wide BMI range) collected from various radiology departments of Geisinger Health System. To our knowledge, this is the first study of its kind on such a large and diverse clinical dataset. Our algorithm obtained a 3.4% error for VAT segmentation compared to manual segmentation. These personalized and accurate measurements of fat can complement traditional population health driven obesity metrics such as BMI and WC.

Enhanced peroxisomal β-oxidation metabolism in visceral adipose tissues of high-fat diet-fed obesity-resistant C57BL/6 mice

PubMed Central

XIE, WEI-DONG; WANG, HUA; ZHANG, JIN-FANG; LI, JIAN-NA; CAN, YI; QING, LV; KUNG, HSIANG-FU; ZHANG, YA-OU

2011-01-01

This study aimed to investigate the potential mechanisms of natural resistance to high-fat diet-induced obesity. Four-week-old C57BL/6 mice were fed a high-fat diet for 6 weeks and were then designated as high-fat diet-fed obesity-prone (HOP) and obesity-resistant (HOR) animals. Their blood biochemistry was evaluated, and visceral adipose tissue samples were subjected to proteomic, Western blot and quantitative real-time PCR (q-PCR) analyses. The HOR mice showed reduced visceral fat weight and size, as well as lowered serum lipid and leptin levels. Proteomic analysis showed that enoyl coenzyme A hydratase 1, peroxisomal (Ech1) expression was significantly increased in their visceral adipose tissues. Moreover, other proteins, such as α-tropomyosin, myosin light chain, urine-nucleoside phosphorylase and transgelin, were also significantly increased. Furthermore, q-PCR analysis showed that the expression of acyl-CoA oxidase 1 palmitoyl, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA thiolase responsible for peroxisomal β-oxidation was also up-regulated in the visceral adipose tissues of the HOR mice. The expression of peroxisome proliferator-activated receptor α (PPARα) was increased in the HOR mice as shown by Western blot analysis. Obesity-resistant animals show enhanced peroxisomal β-oxidation metabolism and reduced fat accumulation in visceral adipose tissues by up-regulating the expression of Ech1, peroxisomal or other related peroxisomal β-oxidation marker genes, which may be driven or enhanced by the up-regulation of the expression of PPARα. However, further validation in future studies is required. PMID:22977503

Uncovering Suitable Reference Proteins for Expression Studies in Human Adipose Tissue with Relevance to Obesity

PubMed Central

Pérez-Pérez, Rafael; López, Juan A.; García-Santos, Eva; Camafeita, Emilio; Gómez-Serrano, María; Ortega-Delgado, Francisco J.; Ricart, Wifredo; Fernández-Real, José M.; Peral, Belén

2012-01-01

Background Protein expression studies based on the two major intra-abdominal human fat depots, the subcutaneous and the omental fat, can shed light into the mechanisms involved in obesity and its co-morbidities. Here we address, for the first time, the identification and validation of reference proteins for data standardization, which are essential for accurate comparison of protein levels in expression studies based on fat from obese and non-obese individuals. Methodology and Findings To uncover adipose tissue proteins equally expressed either in omental and subcutaneous fat depots (study 1) or in omental fat from non-obese and obese individuals (study 2), we have reanalyzed our previously published data based on two-dimensional fluorescence difference gel electrophoresis. Twenty-four proteins (12 in study 1 and 12 in study 2) with similar expression levels in all conditions tested were selected and identified by mass spectrometry. Immunoblotting analysis was used to confirm in adipose tissue the expression pattern of the potential reference proteins and three proteins were validated: PARK7, ENOA and FAA. Western Blot analysis was also used to test customary loading control proteins. ENOA, PARK7 and the customary loading control protein Beta-actin showed steady expression profiles in fat from non-obese and obese individuals, whilst FAA maintained steady expression levels across paired omental and subcutaneous fat samples. Conclusions ENOA, PARK7 and Beta-actin are proper reference standards in obesity studies based on omental fat, whilst FAA is the best loading control for the comparative analysis of omental and subcutaneous adipose tissues either in obese and non-obese subjects. Neither customary loading control proteins GAPDH and TBB5 nor CALX are adequate standards in differential expression studies on adipose tissue. The use of the proposed reference proteins will facilitate the adequate analysis of proteins differentially expressed in the context of obesity, an aim difficult to achieve before this study. PMID:22272336

[Role of chronic inflammation in adipose tissue in the pathophysiology of obesity].

PubMed

Suganami, Takayoshi; Ogawa, Yoshihiro

2013-02-01

Obesity may be viewed as a chronic low-grade inflammatory disease as well as a metabolic disease. Evidence has accumulated suggesting that chronic inflammation in adipose tissue leads to dramatic changes in number and cell type of stromal cells during the course of obesity, which is referred to as"adipose tissue remodeling". Among stromal cells, macrophages in obese adipose tissue are considered to be crucial for adipose tissue inflammation, which results in dysregulated adipocytokine production and ectopic fat accumulation. Understanding the molecular mechanism underlying adipose tissue inflammation would contribute to the identification of novel therapeutic strategies to prevent or treat obesity-induced metabolic derangements.

Anti-obesity effects of hot water extract from Wasabi (Wasabia japonica Matsum.) leaves in mice fed high-fat diets

PubMed Central

Ogawa, Tetsuro; Wang, Li; Katsube, Takuya; Yamasaki, Yukikazu; Sun, Xufeng; Shiwaku, Kuninori

2013-01-01

The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl-isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice were fed a high-fat diet (control group) or a high-fat diet supplemented with 5% WLE (WLE group). Physical parameters and blood profiles were determined. Gene expression associated with lipid metabolism in liver and white adipose tissue were analyzed. After 120 days of feeding, significantly lower body weight gain, liver weight and epididymal white adipose tissue weight was observed in the WLE group compared to the control group. In liver gene expression within the WLE group, PPARα was significantly enhanced and SREBP-1c was significantly suppressed. Subsequent downstream genes controlled by these regulators were significantly suppressed. In epididymal white adipose tissue of the WLE group, expression of leptin, PPARγ, and C/EBPα were significantly suppressed and adiponectin was significantly enhanced. Acox, related to fatty acid oxidization in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary supplement induces mild suppression of obesity in a high-fat diet induced mice, possibly due to suppression of lipid accumulation in liver and white adipose tissue. PMID:23964313

Anti-obesity effects of hot water extract from Wasabi (Wasabia japonica Matsum.) leaves in mice fed high-fat diets.

PubMed

Yamasaki, Masayuki; Ogawa, Tetsuro; Wang, Li; Katsube, Takuya; Yamasaki, Yukikazu; Sun, Xufeng; Shiwaku, Kuninori

2013-08-01

The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl-isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice were fed a high-fat diet (control group) or a high-fat diet supplemented with 5% WLE (WLE group). Physical parameters and blood profiles were determined. Gene expression associated with lipid metabolism in liver and white adipose tissue were analyzed. After 120 days of feeding, significantly lower body weight gain, liver weight and epididymal white adipose tissue weight was observed in the WLE group compared to the control group. In liver gene expression within the WLE group, PPARα was significantly enhanced and SREBP-1c was significantly suppressed. Subsequent downstream genes controlled by these regulators were significantly suppressed. In epididymal white adipose tissue of the WLE group, expression of leptin, PPARγ, and C/EBPα were significantly suppressed and adiponectin was significantly enhanced. Acox, related to fatty acid oxidization in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary supplement induces mild suppression of obesity in a high-fat diet induced mice, possibly due to suppression of lipid accumulation in liver and white adipose tissue.

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

PubMed Central

Wang, Zhigang; Yao, Tong; Pini, Maria; Zhou, Zhanxiang; Fantuzzi, Giamila

2010-01-01

Adipose tissue dysfunction, featured by insulin resistance and/or dysregulated adipokine production, plays a central role not only in disease initiation but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Promising beneficial effects of betaine supplementation on nonalcoholic fatty liver disease (NAFLD) have been reported in both clinical investigations and experimental studies; however, data related to betaine therapy in NAFLD are still limited. In this study, we examined the effects of betaine supplementation on hepatic fat accumulation and injury in mice fed a high-fat diet and evaluated mechanisms underlying its hepatoprotective effects. Male C57BL/6 mice weighing 25 ± 0.5 (SE) g were divided into four groups (8 mice/group) and started on one of four treatments: control diet, control diet supplemented with betaine, high-fat diet, and high-fat diet supplemented with betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Our results showed that long-term high-fat feeding caused NAFLD in mice, which was manifested by excessive neutral fat accumulation in the liver and elevated plasma alanine aminotransferase levels. Betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test, and corrected abnormal adipokine (adiponectin, resistin, and leptin) productions. Specifically, betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signal-regulated kinases 1/2 and protein kinase B activations. In adipocytes freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function. PMID:20203061

White adipose tissue genome wide-expression profiling and adipocyte metabolic functions after soy protein consumption in rats.

PubMed

Frigolet, Maria E; Torres, Nimbe; Uribe-Figueroa, Laura; Rangel, Claudia; Jimenez-Sanchez, Gerardo; Tovar, Armando R

2011-02-01

Obesity is associated with an increase in adipose tissue mass due to an imbalance between high dietary energy intake and low physical activity; however, the type of dietary protein may contribute to its development. The aim of the present work was to study the effect of soy protein versus casein on white adipose tissue genome profiling, and the metabolic functions of adipocytes in rats with diet-induced obesity. The results showed that rats fed a Soy Protein High-Fat (Soy HF) diet gained less weight and had lower serum leptin concentration than rats fed a Casein High-Fat (Cas HF) diet, despite similar energy intake. Histological studies indicated that rats fed the Soy HF diet had significantly smaller adipocytes than those fed the Cas HF diet, and this was associated with a lower triglyceride/DNA content. Fatty acid synthesis in isolated adipocytes was reduced by the amount of fat consumed but not by the type of protein ingested. Expression of genes of fatty acid oxidation increased in adipose tissue of rats fed Soy diets; microarray analysis revealed that Soy protein consumption modified the expression of 90 genes involved in metabolic functions and inflammatory response in adipose tissue. Network analysis showed that the expression of leptin was regulated by the type of dietary protein and it was identified as a central regulator of the expression of lipid metabolism genes in adipose tissue. Thus, soy maintains the size and metabolic functions of adipose tissue through biochemical adaptations, adipokine secretion, and global changes in gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Berberine alleviates adipose tissue fibrosis by inducing AMP-activated kinase signaling in high-fat diet-induced obese mice.

PubMed

Wang, Lijun; Ye, Xiao; Hua, Yanyin; Song, Yingxiang

2018-05-28

Adipose tissue fibrosis is a novel mechanism for the development of obesity related insulin resistance. Berberine (BBR) has been shown to relieve several metabolic disorders, including obesity and type 2 diabetes. However, the effects of BBR on obesity related adipose fibrosis remain poorly understood. The objective of this study was to assess the effects of BBR on adipose tissue fibrosis in high fat diet (HFD)-induced obese mice. The results showed that BBR reduced animal body weight and significantly improved glucose tolerance in HFD mice. In addition, BBR treatment markedly attenuated collagen deposition and reversed the up-regulation of fibrosis associated genes in the adipose tissue of HFD mice. Moreover, BBR treatment activated AMP-activated kinase signaling and reduced TGF-β1 and Smad3 phosphorylation. Of note, the inhibitory effects of BBR on adipose tissue fibrosis were significantly blocked by AMPK inhibition with compound C, an AMPK inhibitor. Macrophage infiltration and polarization induced by HFD were also reversed after BBR administration. These findings suggest that BBR displays beneficial effects in the treatment of obesity, in part via improvement of adipose tissue fibrosis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of dietary fat content, tissue type and sex in adipose and muscle tissues

PubMed Central

2012-01-01

Background DOR/TP53INP2 acts both at the chromosomal level as a nuclear co-factor e.g. for the thyroid hormone receptor and at the extrachromosomal level as an organizing factor of the autophagosome. In a previous study, DOR was shown to be down-regulated in skeletal muscle of obese diabetic Zucker fa/fa rats. Methods To identify sites of differential DOR expression in metabolically active tissues, we measured differences in DOR expression in white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle (SM) and heart muscle (HM) by qPCR. To assess whether DOR expression is influenced in the short term by nutritional factors, NMRI mice were fed different fat rich diets (fat diet, FD: 18% or high fat diet, HFD: 80% fat) for one week and DOR expression was compared to NMRI mice fed a control diet (normal diet, ND: 3.3% fat). Additionally, DOR expression was measured in young (45 days old) and adult (100 days old) genetically obese (DU6/DU6i) mice and compared to control (DUKs/DUKsi) animals. Results ANOVA results demonstrate a significant influence of diet, tissue type and sex on DOR expression in adipose and muscle tissues of FD and HFD mice. In SM, DOR expression was higher in HFD than in FD male mice. In WAT, DOR expression was increased compared to BAT in male FD and HFD mice. In contrast, expression levels in female mice were higher in BAT for both dietary conditions. DOR expression levels in all tissues of 100 days old genetically obese animals were mainly influenced by sex. In HM, DOR expression was higher in male than female animals. Conclusions DOR expression varies under the influence of dietary fat content, tissue type and sex. We identified target tissues for further studies to analyze the specific function of DOR in obesity. DOR might be part of a defense mechanism against fat storage in high fat diets or obesity. PMID:22995226

Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of dietary fat content, tissue type and sex in adipose and muscle tissues.

PubMed

Fromm-Dornieden, Carolin; Lytovchenko, Oleksandr; von der Heyde, Silvia; Behnke, Nina; Hogl, Sebastian; Berghoff, Janina; Köpper, Frederik; Opitz, Lennart; Renne, Ulla; Hoeflich, Andreas; Beissbarth, Tim; Brenig, Bertram; Baumgartner, Bernhard G

2012-09-21

DOR/TP53INP2 acts both at the chromosomal level as a nuclear co-factor e.g. for the thyroid hormone receptor and at the extrachromosomal level as an organizing factor of the autophagosome. In a previous study, DOR was shown to be down-regulated in skeletal muscle of obese diabetic Zucker fa/fa rats. To identify sites of differential DOR expression in metabolically active tissues, we measured differences in DOR expression in white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle (SM) and heart muscle (HM) by qPCR. To assess whether DOR expression is influenced in the short term by nutritional factors, NMRI mice were fed different fat rich diets (fat diet, FD: 18% or high fat diet, HFD: 80% fat) for one week and DOR expression was compared to NMRI mice fed a control diet (normal diet, ND: 3.3% fat). Additionally, DOR expression was measured in young (45 days old) and adult (100 days old) genetically obese (DU6/DU6i) mice and compared to control (DUKs/DUKsi) animals. ANOVA results demonstrate a significant influence of diet, tissue type and sex on DOR expression in adipose and muscle tissues of FD and HFD mice. In SM, DOR expression was higher in HFD than in FD male mice. In WAT, DOR expression was increased compared to BAT in male FD and HFD mice. In contrast, expression levels in female mice were higher in BAT for both dietary conditions.DOR expression levels in all tissues of 100 days old genetically obese animals were mainly influenced by sex. In HM, DOR expression was higher in male than female animals. DOR expression varies under the influence of dietary fat content, tissue type and sex. We identified target tissues for further studies to analyze the specific function of DOR in obesity. DOR might be part of a defense mechanism against fat storage in high fat diets or obesity.

The role of adipose tissue in cancer-associated cachexia.

PubMed

Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing experiments, studies, and clinical trials.

Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

PubMed

Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

2016-06-01

Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure.

PubMed

Holstila, Milja; Pesola, Marko; Saari, Teemu; Koskensalo, Kalle; Raiko, Juho; Borra, Ronald J H; Nuutila, Pirjo; Parkkola, Riitta; Virtanen, Kirsi A

2017-05-01

Brown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water-fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT. The supraclavicular area of 13 volunteers was studied on 3T PET-MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and 18 F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle. The supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by 18 F-FDG PET. Human BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative trait loci segregating in crosses between New Hampshire and White Leghorn chicken lines: III. Fat deposition and intramuscular fat content.

PubMed

Nassar, M K; Goraga, Z S; Brockmann, G A

2013-02-01

In this study, a genome scan was performed to detect genomic loci that affect fat deposition in white adipose tissues and muscles in 278 F (2) males of reciprocal crosses between the genetically and phenotypically extreme inbred chicken lines New Hampshire (NHI) and White Leghorn (WL77). Genome-wide highly significant quantitative trait loci (QTL) influencing fat deposition in white adipose tissues were found on GGA2 and 4. The peak QTL positions for different visceral and subcutaneous white adipose tissues were located between 41.4 and 112.4 Mb on GGA2 and between 76.2 and 78.7 Mb on GGA4, which explained 4.2-10.4% and 4.3-11.6% respectively of the phenotypic F (2) variances. Contrary to our expectations, the QTL allele descending from the lean line WL77 on GGA4 led to increased fat deposition. We suggest a transgressive action of the obesity allele only if it is not in the genetic background of the line WL77. Additional highly significant loci for subcutaneous adipose tissue mass were identified on GGA12 and 15. For intramuscular fat content, a suggestive QTL was located on GGA14. The analysed crosses provide a valuable resource for further fine mapping of fatness genes and subsequent gene discovery. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Investigating the mincing method for isolation of adipose-derived stem cells from pregnant women fat.

PubMed

Li, Yuan-Sheng; Chen, Pao-Jen; Wu, Li-Wei; Chou, Pei-Wen; Sun, Li-Yi; Chiou, Tzyy-Wen

2018-02-01

The success of stem cell application in regenerative medicine, usually require a stable source of stem or progenitor cells. Fat tissue represents a good source of stem cells because it is rich in stem cells and there are fewer ethical issues related to the use of such stem cells, unlike embryonic stem cells. Therefore, there has been increased interest in adipose-derived stem cells (ADSCs) for tissue engineering applications. Here, we aim to provide an easy processing method for isolating adult stem cells from human adipose tissue harvested from the subcutaneous fat of the abdominal wall during gynecologic surgery. We used a homogenizer to mince fat and compared the results with those obtained from the traditional cut method involving a sterile scalpel and forceps. Our results showed that our method provides another stable and quality source of stem cells that could be used in cases with a large quantity of fat. Furthermore, we found that pregnancy adipose-derived stem cells (P-ADSCs) could be maintained in vitro for extended periods with a stable population doubling and low senescence levels. P-ADSCs could also differentiate in vitro into adipogenic, osteogenic, chondrogenic, and insulin-producing cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirates, adipose tissues obtained from pregnant women contain multipotent cells with better proliferation and showed great promise for use in both stem cell banking studies as well as in stem cell therapy.

Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats

PubMed Central

Chen, Jin-Shuen

2017-01-01

Renin–angiotensin system in visceral fat plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. However, the effects of renin inhibition on visceral adiposity in metabolic syndrome are not fully investigated. We investigated the effects of renin inhibition on visceral adiposity in fructose-fed rats. Male Wistar–Kyoto rats were divided into 4 groups for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding, aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced metabolic syndrome, increased visceral fat weights and adipocyte sizes, and augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions, oxidative stress, and dysregulated production of adipocytokines from visceral adipose tissues. Concurrent and subsequent aliskiren administration ameliorated metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and was associated with reducing Ang II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore, this study demonstrates renin inhibition could improve metabolic syndrome, and reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed rats, and suggests that visceral adipose Ang II plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. PMID:28700686

Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats.

PubMed

Chou, Chu-Lin; Lin, Heng; Chen, Jin-Shuen; Fang, Te-Chao

2017-01-01

Renin-angiotensin system in visceral fat plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. However, the effects of renin inhibition on visceral adiposity in metabolic syndrome are not fully investigated. We investigated the effects of renin inhibition on visceral adiposity in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding, aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced metabolic syndrome, increased visceral fat weights and adipocyte sizes, and augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions, oxidative stress, and dysregulated production of adipocytokines from visceral adipose tissues. Concurrent and subsequent aliskiren administration ameliorated metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and was associated with reducing Ang II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore, this study demonstrates renin inhibition could improve metabolic syndrome, and reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed rats, and suggests that visceral adipose Ang II plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats.

ApoE and the role of very low density lipoproteins in adipose tissue inflammation

USDA-ARS?s Scientific Manuscript database

Our goal was too identify the role of triglyceride-rich lipoproteins and apoE, a major apolipoprotein in triglyceride-rich lipoproteins, in adipose tissue inflammation with high-fat diet induced obesity. Male apoE-/- and C57BL/6J wild-type mice fed high fat diets for 12 weeks were assessed for metab...

Thermogenic profiling using magnetic resonance imaging of dermal and other adipose tissues

PubMed Central

Kasza, Ildiko; Hernando, Diego; Roldán-Alzate, Alejandro; Alexander, Caroline M.; Reeder, Scott B.

2016-01-01

Dermal white adipose tissue (dWAT) was recently recognized for its potential to modify whole body metabolism. Here, we show that dWAT can be quantified using a high-resolution, fat-specific magnetic resonance imaging (MRI) technique. Noninvasive MRI has been used to describe adipocyte depots for many years; the MRI technique we describe uses an advanced fat-specific method to measure the thickness of dWAT, together with the total volume of WAT and the relative activation/fat depletion of brown adipose tissues (BAT). Since skin-embedded adipocytes may provide natural insulation, they provide an important counterpoint to the activation of thermogenic brown and beige adipose tissues, whereby these distinct depots are functionally interrelated and require simultaneous assay. This method was validated using characterized mouse cohorts of a lipodystrophic, dWAT-deficient strain (syndecan-1 KO) and 2 obese models (diet-induced obese mice and genetically obese animals, ob/ob). Using a preliminary cohort of normal human subjects, we found the thickness of skin-associated fat varied 8-fold, from 0.13–1.10 cm; on average, this depot is calculated to weigh 8.8 kg. PMID:27668285

Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland

PubMed Central

Alves, Susana P.; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J. B.; Almeida, André M.

2015-01-01

Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

Visceral and Subcutaneous Fat Quality is Associated with Cardiometabolic Risk

PubMed Central

Rosenquist, Klara J.; Pedley, Alison; Massaro, Joseph M.; Therkelsen, Kate E.; Murabito, Joanne M.; Hoffmann, Udo; Fox, Caroline S.

2013-01-01

Objective The aim of this study was to evaluate whether computed tomography (CT) attenuation, as a measure of fat quality, is associated with cardiometabolic risk factors above and beyond fat quantity. Background Visceral (VAT) and subcutaneous adipose tissue (SAT) are pathogenic fat depots associated with cardiometabolic risk. Adipose tissue attenuation in CT images is variable, similar to adipose tissue volume. However, whether the quality of abdominal fat attenuation is associated to cardiometabolic risk independent of the quantity is uncertain. Methods Participants were drawn from the Framingham Heart Study CT sub-study. VAT and SAT volumes were acquired by semi-quantitative assessment. Fat quality was measured by CT attenuation and recorded as mean Hounsfield Units (HU) within each fat depot. Sex-specific linear and logistic multivariable regression models were used to assess the association between standard deviation (SD) decrease in HU and each risk factor. Results Lower CT attenuation of VAT and SAT was correlated with higher BMI levels in both sexes. Risk factors were generally more adverse with decreasing HU values. For example, in women, per 1-SD decrease in VAT HU, the odds ratio (OR) was increased for hypertension (OR 1.80), impaired fasting glucose (OR 2.10), metabolic syndrome (OR 3.65) and insulin resistance (OR 3.36) (all p<0.0001). In models that further adjusted for VAT volume, impaired fasting glucose, metabolic syndrome and insulin resistance remained significant. Trends were similar but less pronounced in SAT and in men. There was evidence of an interaction between HU and fat volume among both women and men. Conclusion Lower CT attenuation of VAT and SAT is associated with adverse cardiometabolic risk above and beyond total adipose tissue volume. Qualitative indices of abdominal fat depots may provide insight regarding cardiometabolic risk independent of fat quantity. PMID:23664720

Intrahepatic fat, abdominal adipose tissues, and metabolic state: magnetic resonance imaging study.

PubMed

Yaskolka Meir, Anat; Tene, Lilac; Cohen, Noa; Shelef, Ilan; Schwarzfuchs, Dan; Gepner, Yftach; Zelicha, Hila; Rein, Michal; Bril, Nitzan; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusy, Benjamin; Dicker, Dror; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2017-07-01

Intrahepatic fat (IHF) is best known to associate with waist circumference (WC) and visceral adipose tissue (VAT), but its relation to abdominal subcutaneous adipose tissue is controversial. While IHF ≥ 5% dichotomously defines fatty liver, %IHF is rarely considered as a continuous variable that includes the normal range. In this study, we aimed to evaluate %IHF association with abdominal fat subdepots, pancreatic, and renal-sinus fats. We evaluated %IHF, abdominal fat subdepots, %pancreatic, and renal-sinus fats, among individuals with moderate abdominal obesity, using 3-Tesla magnetic resonance imaging. Among 275 participants, %IHF widely ranged (0.01%-50.4%) and was lower in women (1.6%) than men (7.3%; P < .001). In an age, sex, and WC-adjusted models, VAT area (P < .006) was directly associated with %IHF, while superficial-subcutaneous adipose tissue proportion was inversely associated with %IHF (P < .006). In these models, renal-sinus fat was positively associated with %IHF (P = .005). In an age, sex, WC, and VAT-adjusted models, elevated liver enzymes, glycemic, lipid, and inflammatory biomarkers were associated with increased %IHF (P < .003 for all). In these models, the associations remained robust even within the normal range strata of IHF < 5% for triglycerides and chemerin (P ≤ .004 for all). For the diagnosis of fatty liver, the joint area under the curve of WC, alanine-aminotransferase, triglycerides/high-density lipoprotein cholesterol, and homeostasis model assessment of insulin resistance was 0.84(95% CI, 0.79-0.89). Intrahepatic fat is differentially associated with abdominal fat subdepots. Intrahepatic-fat as a continuous variable could be predicted by specific traditional parameters, even within the current normal range, and partially independent of VAT. Copyright © 2017 John Wiley & Sons, Ltd.

A Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat

PubMed Central

Kazak, Lawrence; Chouchani, Edward T.; Jedrychowski, Mark P.; Erickson, Brian K.; Shinoda, Kosaku; Cohen, Paul; Vetrivelan, Ramalingam; Lu, Gina Z.; Laznik-Bogoslavski, Dina; Hasenfuss, Sebastian C.; Kajimura, Shingo; Gygi, Steve P.; Spiegelman, Bruce M.

2015-01-01

SUMMARY Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial Creatine Kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole body energy expenditure after administration of a β3-agonist and reduces the adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PMID:26496606

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

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

The role of adenosine monophosphate kinase in remodeling white adipose tissue metabolism.

PubMed

Gaidhu, Mandeep Pinky; Ceddia, Rolando Bacis

2011-04-01

Recent evidence indicates that the enzyme adenosine monophosphate (AMP) kinase exerts important fat-reducing effects in the adipose tissue, which has created great interest in this enzyme as a potential target for obesity treatment. This review summarizes our findings that chronic AMP kinase activation remodels adipocyte glucose and lipid metabolism and enhances the ability of adipose tissue to dissipate energy within itself and reduce adiposity.

Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting

PubMed Central

2012-01-01

Background Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens. Results We combined transcriptomics and metabolomics to characterize the response of chicken adipose tissue to two energy manipulations, fasting and insulin deprivation in the fed state. Sixteen to 17 day-old commercial broiler chickens (ISA915) were fed ad libitum, fasted for five hours, or fed but deprived of insulin by injections of anti-insulin serum. Pair-wise contrasts of expression data identified a total of 2016 genes that were differentially expressed after correction for multiple testing, with the vast majority of differences due to fasting (1780 genes). Gene Ontology and KEGG pathway analyses indicated that a short term fast impacted expression of genes in a broad selection of pathways related to metabolism, signaling and adipogenesis. The effects of insulin neutralization largely overlapped with the response to fasting, but with more modest effects on adipose tissue metabolism. Tissue metabolomics indicated unique effects of insulin on amino acid metabolism. Conclusions Collectively, these data provide a foundation for further study into the molecular basis for adipose expansion in commercial poultry and identify potential pathways through which fat accretion may be attenuated in the future through genetic selection or management practices. They also highlight chicken as a useful model organism in which to study the dynamic relationship between food intake, metabolism, and adipose tissue biology. PMID:22938590

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...

Effects of Erythropoietin on Adipose Tissue: A Possible Strategy in Refilling

PubMed Central

Sabbatini, Maurizio; Bosetti, Michela; Borrone, Alessia; Boldorini, Renzo; Taveggia, Antonio; Verna, Giovanni; Cannas, Mario

2015-01-01

Background: The increased resorption and the difficulty of the fat graft take following autologous fat transplantation procedure are associated with reduced fat tissue revascularization and increased apoptosis of adipose cells. We suppose that the lipofilling procedure induces an inflammatory environment within the fat graft mass, whose evolution influences the efficacy of autologous fat graft survival. Erythropoietin (EPO) is a glycoprotein hormone known to exert angiogenetic and anti-inflammatory effects; therefore, our purpose was to investigate its reaction with adipose tissue used in lipofilling. Methods: Fat masses were harvested using manual suction lipectomy and then seeded on dishes in appropriate culture and treated for 3 weeks with 3 doses of EPO. CD31 and CD68 immunohistochemistry was used to identify microvessels and several infiltrating leukocyte cells. Results: Following EPO administration, we have detected an increase in the number of CD31-positive microvessel endothelium cells and CD31-positive small leukocytes and a reduction of CD68-positive cells. These effects were more conspicuous following higher EPO dose. Conclusions: Our findings evidence EPO treatment as a useful strategy to sustain the revascularization of grafted tissue and to reduce its inflammatory state. PMID:26034645

PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue.

PubMed

Matsubara, Toshiya; Mita, Ayako; Minami, Kohtaro; Hosooka, Tetsuya; Kitazawa, Sohei; Takahashi, Kenichi; Tamori, Yoshikazu; Yokoi, Norihide; Watanabe, Makoto; Matsuo, Ei-Ichi; Nishimura, Osamu; Seino, Susumu

2012-01-04

Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn(-/-)) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity. Copyright © 2012 Elsevier Inc. All rights reserved.

Fatty Acid Composition of Lamb Liver, Muscle, And Adipose Tissues in Response to Rumen-Protected Conjugated Linoleic Acid (CLA) Supplementation Is Tissue Dependent.

PubMed

Schiavon, Stefano; Bergamaschi, Matteo; Pellattiero, Erika; Simonetto, Alberto; Tagliapietra, Franco

2017-12-06

The tissue-specific response to rumen-protected conjugated linoleic acid supply (rpCLA) of liver, two muscles, and three adipose tissues of heavy lambs was studied. Twenty-four lambs, 8 months old, divided into 4 groups of 6, were fed at libitum on a ration supplemented without or with a mixture of rpCLA. Silica and hydrogenated soybean oil was the rpCLA coating matrix. The lambs were slaughtered at 11 months of age. Tissues were collected and analyzed for their FA profiles. The dietary rpCLA supplement had no influence on carcass fatness nor on the fat content of the liver and tissues and had little influence on the FA profiles of these tissues. In the adipose tissues, rpCLA increased the proportions of saturated FAs, 18:0 and 18:2t10c12, and decreased the proportions of monounsaturated FAs in the adipose tissues. In muscles, the effects were the opposite. The results suggest that Δ9 desaturase activity is inhibited by the rpCLA mixture in adipose tissues to a greater extent than in the other tissues.

Disconnect Between Adipose Tissue Inflammation and Cardiometabolic Dysfunction in Ossabaw Pigs

PubMed Central

Vieira-Potter, Victoria J.; Lee, Sewon; Bayless, David S.; Scroggins, Rebecca J.; Welly, Rebecca J.; Fleming, Nicholas J.; Smith, Thomas N.; Meers, Grace M.; Hill, Michael A.; Rector, R. Scott; Padilla, Jaume

2015-01-01

Objective The Ossabaw pig is emerging as an attractive model of human cardiometabolic disease due to its size and susceptibility to atherosclerosis, among other characteristics. Here we investigated the relationship between adipose tissue inflammation and metabolic dysfunction in this model. Methods Young female Ossabaw pigs were fed a western-style high-fat diet (HFD) (n=4) or control low-fat diet (LFD) (n=4) for a period of 9 months and compared for cardiometabolic outcomes and adipose tissue inflammation. Results The HFD-fed “OBESE” pigs were 2.5 times heavier (p<0.001) than LFD-fed “LEAN” pigs and developed severe obesity. HFD-feeding caused pronounced dyslipidemia, hypertension, insulin resistance (systemic and adipose) as well as induction of inflammatory genes, impairments in vasomotor reactivity to insulin and atherosclerosis in the coronary arteries. Remarkably, visceral, subcutaneous and perivascular adipose tissue inflammation (via FACS analysis and RT-PCR) was not increased in OBESE pigs, nor were circulating inflammatory cytokines. Conclusions These findings reveal a disconnect between adipose tissue inflammation and cardiometabolic dysfunction induced by western diet feeding in the Ossabaw pig model. PMID:26524201

Adipose tissue MRI for quantitative measurement of central obesity.

PubMed

Poonawalla, Aziz H; Sjoberg, Brett P; Rehm, Jennifer L; Hernando, Diego; Hines, Catherine D; Irarrazaval, Pablo; Reeder, Scott B

2013-03-01

To validate adipose tissue magnetic resonance imaging (atMRI) for rapid, quantitative volumetry of visceral adipose tissue (VAT) and total adipose tissue (TAT). Data were acquired on normal adults and clinically overweight girls with Institutional Review Board (IRB) approval/parental consent using sagittal 6-echo 3D-spoiled gradient-echo (SPGR) (26-sec single-breath-hold) at 3T. Fat-fraction images were reconstructed with quantitative corrections, permitting measurement of a physiologically based fat-fraction threshold in normals to identify adipose tissue, for automated measurement of TAT, and semiautomated measurement of VAT. TAT accuracy was validated using oil phantoms and in vivo TAT/VAT measurements validated with manual segmentation. Group comparisons were performed between normals and overweight girls using TAT, VAT, VAT-TAT-ratio (VTR), body-mass-index (BMI), waist circumference, and waist-hip-ratio (WHR). Oil phantom measurements were highly accurate (<3% error). The measured adipose fat-fraction threshold was 96% ± 2%. VAT and TAT correlated strongly with manual segmentation (normals r(2) ≥ 0.96, overweight girls r(2) ≥ 0.99). VAT segmentation required 30 ± 11 minutes/subject (14 ± 5 sec/slice) using atMRI, versus 216 ± 73 minutes/subject (99 ± 31 sec/slice) manually. Group discrimination was significant using WHR (P < 0.001) and VTR (P = 0.004). The atMRI technique permits rapid, accurate measurements of TAT, VAT, and VTR. Copyright © 2012 Wiley Periodicals, Inc.

Distribution of volatile branched-chain fatty acids in various lamb tissues.

PubMed

Brennand, C P; Lindsay, R C

1992-01-01

Volatile fatty acids (C4-C11) including even-, odd-, and branched-chain members in lamb tissues were quantitatively analyzed. Volatile branched-chain fatty acids (BCFA) were more concentrated in subcutaneous adipose tissue samples (rump, shoulder, breast) than in perinepheric adipose or muscle tissues. Perinepheric adipose tissue contained relatively high quantities of n-chain, even-numbered fatty acids and very low levels of BCFA. Greater variation existed in fatty acid profiles among similar subcutaneous adipose tissues from different lambs than between samples of adipose tissue from different carcass sites from a given lamb sample. 4-Methyl- and 4-ethyloctanoic acids were present at concentrations greatly above threshold levels in all lamb fats tested, and thus upon hydrolysis would contribute species-related flavors to lamb. 4-Methylnonanoic concentrations in lamb fats ranged from nondetectable to greater than the threshold level, and therefore this compound would not always contribute to the species-related flavors of lamb. Lean meat samples contained very low concentrations of 4-methyl- and 4-ethyloctanoic acids. Copyright © 1992. Published by Elsevier Ltd.

Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans.

PubMed

Gavaldà-Navarro, Aleix; Moreno-Navarrete, José M; Quesada-López, Tania; Cairó, Montserrat; Giralt, Marta; Fernández-Real, José M; Villarroya, Francesc

2016-10-01

Adipocyte lipopolysaccharide-binding protein (LBP) biosynthesis is associated with obesity-induced adipose tissue dysfunction. Our purpose was to study the role of LBP in regulating the browning of adipose tissue. Adult mice were maintained at 4°C for 3 weeks or treated with the β3-adrenergic agonist, CL316,243, for 1 week to induce the browning of white fat. Precursor cells from brown and white adipose tissues were cultured under differentiation-inducing conditions to yield brown and beige/brite adipocytes, respectively. In vitro, Lbp was knocked down in 3T3-L1 adipocytes, and cells were treated with recombinant LBP or co-cultured in transwells with control 3T3-L1 adipocytes. Wild-type and Lbp-null mice, fed a standard or high fat diet (HFD) for 15 weeks, were also used in investigations. In humans, subcutaneous and visceral adipose tissue samples were obtained from a cohort of morbidly obese participants. The induction of white fat browning by exposure of mice to cold or CL316,243 treatment was strongly associated with decreased Lbp mRNA expression in white adipose tissue. The acquisition of the beige/brite phenotype in cultured cells was associated with downregulation of Lbp. Moreover, silencing of Lbp induced the expression of brown fat-related genes in adipocytes, whereas LBP treatment reversed this effect. Lbp-null mice exhibited the spontaneous induction of subcutaneous adipose tissue browning, as evidenced by a remarkable increase in Ucp1 and Dio2 gene expression and the appearance of multivacuolar adipocyte clusters. The amount of brown adipose tissue, and brown adipose tissue activity were also increased in Lbp-null mice. These changes were associated with decreased weight gain in Lbp-null mice and protection against HFD-induced inflammatory responses, as shown by reduced IL-6 levels. However, rather than improving glucose homeostasis, these effects led to glucose intolerance and insulin resistance. LBP is identified as a negative regulator of the browning process, which is likely to contribute to the obesity-promoting action of LBP. The deleterious metabolic effects of LBP deletion are compatible with the concept that the appropriate regulation of inflammatory pathways is necessary for a healthy systemic metabolic profile, regardless of body weight regulation.

Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice.

PubMed

Braster, Quinte; Silvestre Roig, Carlos; Hartwig, Helene; Beckers, Linda; den Toom, Myrthe; Döring, Yvonne; Daemen, Mat J; Lutgens, Esther; Soehnlein, Oliver

2016-01-01

Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs may be relevant to early adipose tissue inflammation. Thus, we tested the effect of the Peptidyl Arginine Deiminase 4 inhibitor Cl-amidine, a compound preventing histone citrullination and subsequent NET release, in a mouse model of adipose tissue inflammation. C57BL6 mice received a 60% high fat diet for 10 weeks and were treated with either Cl-amidine or vehicle. Flow cytometry of adipose tissue and liver, immunohistological analysis and glucose and insulin tolerance tests were performed to determine the effect of the treatment and diet. Although high fat diet feeding induced insulin resistance no significant effect was observed between the treatment groups. In addition no effect was found in leukocyte infiltration and activation in the adipose tissue and liver. Therefore we concluded that inhibition of neutrophil extracellular trap formation may have no clinical relevance for early obesity-mediated pathogenesis of the adipose tissue and liver.

Interferon beta overexpression attenuates adipose tissue inflammation and high-fat diet-induced obesity and maintains glucose homeostasis.

PubMed

Alsaggar, M; Mills, M; Liu, D

2017-01-01

The worldwide prevalence of obesity is increasing, raising health concerns regarding obesity-related complications. Chronic inflammation has been characterized as a major contributor to the development of obesity and obesity-associated metabolic disorders. The purpose of the current study is to assess whether the overexpression of interferon beta (IFNβ1), an immune-modulating cytokine, will attenuate high-fat diet-induced adipose inflammation and protect animals against obesity development. Using hydrodynamic gene transfer to elevate and sustain blood concentration of IFNβ1 in mice fed a high-fat diet, we showed that the overexpression of Ifnβ1 gene markedly suppressed immune cell infiltration into adipose tissue, and attenuated production of pro-inflammatory cytokines. Systemically, IFNβ1 blocked adipose tissue expansion and body weight gain, independent of food intake. Possible browning of white adipose tissue might also contribute to blockade of weight gain. More importantly, IFNβ1 improved insulin sensitivity and glucose homeostasis. These results suggest that targeting inflammation represents a practical strategy to block the development of obesity and its related pathologies. In addition, IFNβ1-based therapies have promising potential for clinical applications for the prevention and treatment of various inflammation-driven pathologies.

Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue

PubMed Central

Huang, Edmond; Leone, Vanessa; Devkota, Suzanne; Wang, Yunwei; Brady, Matthew; Chang, Eugene

2013-01-01

Background Growing evidence shows that dietary factors can dramatically alter the gut microbiome in ways that contribute to metabolic disturbance and progression of obesity. In this regard, mesenteric adipose tissue has been implicated in mediating these processes through the elaboration of pro-inflammatory adipokines. In this study, we examined the relationship of these events by determining the effects of dietary fat content and source on gut microbiota, as well as the effects on adipokine profiles of mesenteric and peripheral adipocytes. Methods Adult male C57Bl/6 mice were fed milk fat-, lard-(SFA sources), or safflower oil (PUFA)- based high fat diets for four weeks. Body mass and food consumption were measured. Stool 16S rRNA was isolated and analyzed via T-RFLP as well as variable V3-4 sequence tags via next gen sequencing. Mesenteric and gonadal adipose samples were analyzed for both lipogenic and inflammatory mediators via qRT-PCR. Results High-fat feedings caused more weight gain with concomitant increases in caloric consumption relative to low-fat diets. Additionally, each of the high fat diets induced dramatic and specific 16S rRNA phylogenic profiles that were associated with different inflammatory and lipogenic mediator profile of mesenteric and gonadal fat depots. Conclusions Our findings support the notion that dietary fat composition can both reshape the gut microbiota as well as alter host adipose tissue inflammatory/lipogenic profiles. They also demonstrate the interdependency of dietary fat source, commensal gut microbiota, and inflammatory profile of mesenteric fat that can collectively impact the host metabolic state. PMID:23639897

The role of brown adipose tissue in temperature regulation. [of hibernating and hypothermic mammals

NASA Technical Reports Server (NTRS)

Smith, R. E.

1973-01-01

The thermogenetic capacities of brown adipose tissue were studied on marmots, rats and monkeys in response to cold exposure. All experiments indicated that the brown fat produced heat and slowed the cooling of tissues.

Canine body composition quantification using 3 tesla fat-water MRI.

PubMed

Gifford, Aliya; Kullberg, Joel; Berglund, Johan; Malmberg, Filip; Coate, Katie C; Williams, Phillip E; Cherrington, Alan D; Avison, Malcolm J; Welch, E Brian

2014-02-01

To test the hypothesis that a whole-body fat-water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet. Six healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach. Volumes were converted to masses using published tissue densities. FWMRI-derived total mass corresponds with scale mass with a concordance correlation coefficient of 0.931 (95% confidence interval = [0.813, 0.975]), and slope and intercept values of 1.12 and -2.23 kg, respectively. Visceral, subcutaneous and total adipose tissue masses increased significantly from weeks 0 to 4, while neither cortical bone nor lean tissue masses changed significantly. This is evidenced by a mean percent change of 70.2% for visceral, 67.0% for subcutaneous, and 67.1% for total adipose tissue. FWMRI can precisely quantify and map body composition with respect to adipose, lean, and bone tissue depots. The described approach provides a valuable tool to examine the role of distinct tissue depots in an established animal model of human metabolic disease. Copyright © 2013 Wiley Periodicals, Inc.

Weight-dependent changes of immune system in adipose tissue: Importance of leptin

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

Caspar-Bauguil, S.; Groupe de Recherche et d'Etude en Nutrition; Cousin, B.

2006-07-15

Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage ofmore » NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral {gamma}{delta} T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the {alpha}{beta} T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.« less

A role of low dose chemical mixtures in adipose tissue in carcinogenesis.

PubMed

Lee, Duk-Hee; Jacobs, David R; Park, Ho Yong; Carpenter, David O

2017-11-01

The Halifax project recently hypothesized a composite carcinogenic potential of the mixture of low dose chemicals which are commonly encountered environmentally, yet which are not classified as human carcinogens. A long neglected but important fact is that adipose tissue is an important exposure source for chemical mixtures. In fact, findings from human studies based on several persistent organic pollutants in general populations with only background exposure should be interpreted from the viewpoint of chemical mixtures because serum concentrations of these chemicals can be seen as surrogates for chemical mixtures in adipose tissue. Furthermore, in conditions such as obesity with dysfunctional adipocytes or weight loss in which lipolysis is increased, the amount of the chemical mixture released from adipose tissue to circulation is increased. Thus, both obesity and weight loss can enhance the chance of chemical mixtures reaching critical organs, however paradoxical this idea may be when fat mass is the only factor considered. The complicated, interrelated dynamics of adipocytes and chemical mixtures can explain puzzling findings related to body weight among cancer patients, including the obesity paradox. The contamination of fat in human diet with chemical mixtures, occurring for reasons similar to contamination of human adipose tissue, may be a missing factor which affects the association between dietary fat intake and cancer. The presence of chemical mixtures in adipose tissue should be considered in future cancer research, including clinical trials on weight management among cancer survivors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Responses to peripheral neuropeptide Y in avian adipose tissue are diet, depot, and time specific.

PubMed

Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

2018-06-01

The goal of this research was to determine the effect of dietary macronutrient composition on peripheral neuropeptide Y (NPY)-induced changes in adipose tissue dynamics in chicks. Chicks were fed one of three isocaloric diets from the day of hatch: high carbohydrate (HC), high fat (HF), or high protein (HP). On day 4 post-hatch, 0 (vehicle), 60, or 120 µg/kg BW of NPY was injected intraperitoneally, and subcutaneous, clavicular and abdominal adipose tissue samples were collected at 1 and 3 h post-injection. The effect of NPY was most pronounced in chicks fed the HF or HP diet. In the subcutaneous fat at 1 h post-injection, 60 µg/kg BW of NPY was associated with an increase in NPY receptor 2 (NPYR2) mRNA in chicks fed the HP diet and a decrease in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) mRNA in chicks fed the HC diet. In response to 120 µg/kg BW of NPY, there was greater AGPAT2 mRNA in the clavicular fat of chicks that consumed the HP diet and less CCAAT/enhancer-binding protein alpha in the abdominal fat of chicks that were provided the HF diet. There were no gene expression changes in the abdominal fat at 3 h post-injection, whereas there were decreases in AGPAT2, adipose triglyceride lipase, fatty acid binding protein 4 and NPY mRNA in the clavicular fat of chicks fed the HP diet. Results demonstrate that diet affects exogenous NPY-dependent physiological effects in a time- and depot-dependent manner in chick adipose tissue. Copyright © 2018 Elsevier Inc. All rights reserved.

The Effects of Gymnema sylvestre in High-Fat Diet-Induced Metabolic Disorders.

PubMed

Kim, Hyeon-Jeong; Kim, Sanghwa; Lee, Ah Young; Jang, Yoonjeong; Davaadamdin, Orkhonselenge; Hong, Seong-Ho; Kim, Jun Sung; Cho, Myung-Haing

2017-01-01

This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500[Formula: see text]mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.

Removal of mouse ovary fat pad affects sex hormones, folliculogenesis and fertility.

PubMed

Wang, Hong-Hui; Cui, Qian; Zhang, Teng; Guo, Lei; Dong, Ming-Zhe; Hou, Yi; Wang, Zhen-Bo; Shen, Wei; Ma, Jun-Yu; Sun, Qing-Yuan

2017-02-01

As a fat storage organ, adipose tissue is distributed widely all over the body and is important for energy supply, body temperature maintenance, organ protection, immune regulation and so on. In humans, both underweight and overweight women find it hard to become pregnant, which suggests that appropriate fat storage can guarantee the female reproductive capacity. In fact, a large mass of adipose tissue distributes around the reproductive system both in the male and female. However, the functions of ovary fat pad (the nearest adipose tissue to ovary) are not known. In our study, we found that the ovary fat pad-removed female mice showed decreased fertility and less ovulated mature eggs. We further identified that only a small proportion of follicles developed to antral follicle, and many follicles were blocked at the secondary follicle stage. The overall secretion levels of estrogen and FSH were lower in the whole estrus cycle (especially at proestrus); however, the LH level was higher in ovary fat pad-removed mice than that in control groups. Moreover, the estrus cycle of ovary fat pad-removed mice showed significant disorder. Besides, the expression of FSH receptor decreased, but the LH receptor increased in ovary fat pad-removed mice. These results suggest that ovary fat pad is important for mouse reproduction. © 2017 Society for Endocrinology.

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.

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

PubMed

Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral capsaicin effect at one remote site. There was an accompanying decrease and an increase in the proportion of body fat in visceral and subcutaenous compartments, respectively. Taken together, if oral capsaicin could regulate adipose tissue distribution, the process might involve the effect of intestinal mucosal afferent nerves in modulating intestinal and visceral adipose tissue blood flow. The hypothesis that the intestinal mucosal afferent mechanism is a plausible therapeutic target for abating visceral obesity deserves to be further evaluated.

Comparison of labeled acetate and glucose incorporations into lipids in the liver and adipose tissue after intravenous injection in rats.

PubMed

Iritani, Nobuko; Hirakawa, Tomoe; Fukuda, Hitomi; Katsukawa, Michiko; Kouno, Mika

2014-01-01

To compare incorporations of acetate and glucose in tissue total lipids and triacylglycerols (TAG), incorporations of labeled acetate and glucose in livers and epididymal adipose tissues (adipose tissue) were followed after their intravenous injection in the tail vein of individual rat fed a fat-free or 10% corn oil diet. The incorporation of acetate into total lipids (mostly TAG) in the liver reached maximum 2 h after the injection, while the incorporation of glucose decreased more quickly. Incorporation of glucose into total lipids and TAG was more greatly suppressed by dietary corn oil than that of acetate in the liver. In the adipose tissues, the incorporation of labeled acetate or glucose into total lipids was maximum 2-8 h after the injection, while the incorporation of glucose was very low, especially in rats fed the corn oil diet. Moreover, the time courses for labeled acetate and glucose incorporations into total lipids in the liver were parallel to those in plasma, but opposite to those in adipose tissue. TAG synthesized from acetate and glucose in the liver appeared to be mostly transported to adipose tissue. Thus, it is suggested that as the labeled glucose rapidly decreased in the liver, plasma and adipose tissue, TAG should be less derived from dietary carbohydrate than from dietary fat.

Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

PubMed Central

Alexander, Robert W; Harrell, David B

2013-01-01

Objectives Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF) for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG) with use of disposable, microcannula systems. Design Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are available as safe, sterile, disposable, compact systems for acquiring high-quality AFG. Presented is a detailed, step-by-step, proven protocol for performing quality autologous structural adipose transplantation. PMID:23630430

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

Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

PubMed

Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

2015-12-01

In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Not all fats are created equal: adipose vs. ectopic fat, implication in cardiometabolic diseases.

PubMed

Gaggini, Melania; Saponaro, Chiara; Gastaldelli, Amalia

2015-04-01

Adipose tissue is a recognized endocrine organ that acts not only as a fuel storage but also is able to secrete adipokines that can modulate inflammation. Most of the fat is composed of white adipocytes (WAT), although also brown/beige adipocytes (BAT/BeAT) have been found in humans. BAT is located close to the neck but also among WAT in the epicardial fat and perivascular fat. Adipocyte hypertrophy and infiltration of macrophages impair adipose tissue metabolism determining "adiposopathy" (i.e., sick fat) and increasing the risk to develop metabolic and cardiovascular diseases. The purpose of this review was to search and discuss the available literature on the impact of different types of fat and fat distribution on cardiometabolic risk. Visceral fat, but also ectopic fat, either in liver, muscle and heart, can increase the risk to develop insulin resistance, type 2 diabetes and cardiovascular diseases. Results recently published showed that BAT could have an impact on cardiometabolic risk, not only because it is implicated in energy metabolism but also because it can modulate glucose and lipid metabolism. Therapeutical interventions that can increase energy expenditure, successfully change fat distribution and reduce ectopic fat, also through BAT activation, were discussed.

Cell-assisted lipotransfer in the clinical treatment of facial soft tissue deformity

PubMed Central

Ma, Li; Wen, Huicai; Jian, Xueping; Liao, Huaiwei; Sui, Yunpeng; Liu, Yanping; Xu, Guizhen

2015-01-01

Cosmetic surgeons have experimented with a variety of substances to improve soft tissue deformities of the face. Autologous fat grafting provides significant advantages over other modalities because it leaves no scar, is easy to use and is well tolerated by most patients. Autologous fat grafting has become one of the most popular techniques in the field of facial plastic surgery. Unfortunately, there are still two major problems affecting survival rate and development: revascularization after transplantion; and cell reservation proliferation and survival. Since Zuk and Yosra developed a technology based on adipose-derived stem cells and cell-assisted lipotrophy, researchers have hoped that this technology would promote the survival and reduce the absorption of grafted fat cells. Autologous adipose-derived stem cells may have great potential in skin repair applications, aged skin rejuvenation and other aging-related skin lesion treatments. Recently, the study of adipose-derived stem cells has gained increased attention. More researchers have started to adopt this technology in the clinical treatment of facial soft tissue deformity. The present article reviews the history of facial soft tissue augmentation and the advent of adipose-derived stem cells in the area of the clinical treatment of facial soft tissue deformity. PMID:26361629

Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease.

PubMed

Burke, Shoshana; Nagajyothi, Fnu; Thi, Mia M; Hanani, Menachem; Scherer, Philipp E; Tanowitz, Herbert B; Spray, David C

2014-11-01

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. Copyright © 2014. Published by Elsevier Masson SAS.

Mycobacterium tuberculosis infection modulates adipose tissue biology

PubMed Central

Kühl, Anja A.; Kupz, Andreas; Vogelzang, Alexis; Mollenkopf, Hans-Joachim; Löwe, Delia; Bandermann, Silke; Dorhoi, Anca; Brinkmann, Volker

2017-01-01

Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extrapulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection. Mice infected via aerosol showed infiltration of inducible nitric oxide synthase (iNOS) or arginase 1 (Arg1)-negative F4/80+ cells, despite recruitment of CD3+, CD4+ and CD8+ T cells. Gene expression analysis of adipose tissue of aerosol Mtb-infected mice provided evidence for upregulated expression of genes associated with T cells and NK cells at 28 days post-infection. Strikingly, IFN-γ-producing NK cells and Mtb-specific CD8+ T cells were identified in perigonadal fat, specifically CD8+CD44-CD69+ and CD8+CD44-CD103+ subpopulations. Gene expression analysis of these cells revealed that they expressed IFN-γ and the lectin-like receptor Klrg1 and down-regulated CD27 and CD62L, consistent with an effector phenotype of Mtb-specific CD8+ T cells. Sorted NK cells expressed higher abundance of Klrg1 upon infection, as well. Our results reveal the ability of Mtb to persist in adipose tissue in a stressed state, and that NK cells and Mtb-specific CD8+ T cells infiltrate infected adipose tissue where they produce IFN-γ and assume an effector phenotype. We conclude that adipose tissue is a potential niche for Mtb and that due to infection CD8+ T cells and NK cells are attracted to this tissue. PMID:29040326

Positive interaction between prebiotics and thiazolidinedione treatment on adiposity in diet-induced obese mice.

PubMed

Alligier, Maud; Dewulf, Evelyne M; Salazar, Nuria; Mairal, Aline; Neyrinck, Audrey M; Cani, Patrice D; Langin, Dominique; Delzenne, Nathalie M

2014-07-01

To investigate whether inulin-type fructan (ITF) prebiotics could counteract the thiazolidinedione (TZD, PPARγ activator) induced-fat mass gain, without affecting its beneficial effect on glucose homeostasis, in high-fat (HF) diet fed mice. Male C57bl6/J mice were fed a HF diet alone or supplemented with ITF prebiotics (0.2 g/day × mouse) or TZD (30 mg pioglitazone (PIO)/kg body weight × day) or both during 4 weeks. An insulin tolerance test was performed after 3 weeks of treatment. As expected, PIO improved glucose homeostasis and increased adiponectinaemia. Furthermore, it induced an over-expression of several PPARγ target genes in white adipose tissues. ITF prebiotics modulated the PIO-induced PPARγ activation in a tissue-dependent manner. The co-treatment with ITF prebiotics and PIO maintained the beneficial impact of TZD on glucose homeostasis and adiponectinaemia. Moreover, the combination of both treatments reduced fat mass accumulation, circulating lipids and hepatic triglyceride content, suggesting an overall improvement of metabolism. Finally, the co-treatment favored induction of white-to-brown fat conversion in subcutaneous adipose tissue, thereby leading to the development of brite adipocytes that could increase the oxidative capacity of the tissue. ITF prebiotics decrease adiposity and improve the metabolic response in HF fed mice treated with TZD. © 2014 The Obesity Society.

Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue.

PubMed

Minchin, James E N; Dahlman, Ingrid; Harvey, Christopher J; Mejhert, Niklas; Singh, Manvendra K; Epstein, Jonathan A; Arner, Peter; Torres-Vázquez, Jesús; Rawls, John F

2015-04-07

Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafish to show that Plxnd1 regulates body fat distribution and insulin sensitivity. Plxnd1 deficiency in zebrafish induced hyperplastic morphology in visceral adipose tissue (VAT) and reduced lipid storage. In contrast, subcutaneous adipose tissue (SAT) growth and morphology were unaffected, resulting in altered body fat distribution and a reduced VAT:SAT ratio in zebrafish. A VAT-specific role for Plxnd1 appeared conserved in humans, as PLXND1 mRNA was positively associated with hypertrophic morphology in VAT, but not SAT. In zebrafish plxnd1 mutants, the effect on VAT morphology and body fat distribution was dependent on induction of the extracellular matrix protein collagen type V alpha 1 (col5a1). Furthermore, after high-fat feeding, zebrafish plxnd1 mutant VAT was resistant to expansion, and excess lipid was disproportionately deposited in SAT, leading to an even greater exacerbation of altered body fat distribution. Plxnd1-deficient zebrafish were protected from high-fat-diet-induced insulin resistance, and human VAT PLXND1 mRNA was positively associated with type 2 diabetes, suggesting a conserved role for PLXND1 in insulin sensitivity. Together, our findings identify Plxnd1 as a novel regulator of VAT growth, body fat distribution, and insulin sensitivity in both zebrafish and humans.

BDNF levels in adipose tissue and hypothalamus were reduced in mice with MSG-induced obesity.

PubMed

Jin, Yong Jun; Cao, Peng Juan; Bian, Wei Hua; Li, Ming E; Zhou, Rong; Zhang, Ling Yun; Yang, Mei Zi

2015-01-01

To observe the expression of brain-derived neurotrophic factor (BDNF) in hypothalamic and adipose tissue in mice with monosodium glutamate (MSG)-induced obesity. The effects of hypothalamic lesions, specifically arcuate nucleus (ARC) lesions, induced by MSG injection were studied in male ICR mice at the neonatal stage. The following parameters were compared: body weight, body length, Lee's index, food intake, body temperature, fat weight, and levels of total cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and blood glucose (GLU). The BDNF expression levels in hypothalamic and adipose tissue were measured using western blotting. Results Compared with the control group, the model group body had significantly higher weight, Lee's index, food intake, fat weight, CHOL, TG, LDL, HDL, and GLU levels. BDNF expression levels in hypothalamic and adipose tissue were markedly down-regulated in the model group. BDNF may be closely associated with MSG-induced hypothalamic obesity.

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.

Fatty acid profiles and adipogenic gene expression of various fat depots in Japanese Black and Holstein steers.

PubMed

Shirouchi, Bungo; Albrecht, Elke; Nuernberg, Gerd; Maak, Steffen; Olavanh, Samadmanivong; Nakamura, Yoshinori; Sato, Masao; Gotoh, Takafumi; Nuernberg, Karin

2014-01-01

Objective of the study was to assess the breed effect on fatty acid (FA) composition of different adipose tissues and on mRNA expression of genes involved in adipogenesis and fat metabolism. Japanese Black (JB) and Holstein (HS) steers were kept under equivalent conditions with high energy intake resulting in large differences in intramuscular fat (IMF) accumulation in longissimus muscle (LM). The relative FA composition of muscle, intermuscular fat, visceral fat, and perirenal fat was comparable between JB and HS steers. Circulating fatty acids were also similar in both breeds. Most relevant breed effects were identified in IMF, underlining the uniqueness of this adipose tissue site. JB steers had more monounsaturated FA and less saturated FA. Perilipin 1 and adipose differentiation-related protein (ADFP) mRNA levels were higher in IMF of JB. The results suggest advanced maturity of IMF cells in JB and altered local conditions in muscle influencing IMF accumulation and composition. © 2013.

Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

PubMed

Frigolet, María E; Torres, Nimbe; Tovar, Armando R

2012-01-01

Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities.

Role of Fat and Bone Biomarkers in the Relationship Between Ethnicity and Bone Mineral Density in Older Men.

PubMed

Chan, Grace M F; Riandini, Tessa; Ng, Sheryl Hui Xian; Goh, Su Yen; Tan, Chuen Seng; Tai, E Shyong; Duque, Gustavo; Ng, Alvin Choon-Meng; Venkataraman, Kavita

2018-01-01

Osteoporosis is an important health issue for older adults, and has been relatively understudied in older men. This study aimed to examine ethnic differences in bone mineral density (BMD), and elucidate the role of bone turnover markers (BTMs), fat and fat biomarkers on these ethnic differences. BMD at the lumbar spine and femoral neck, marrow fat at femoral neck, visceral adipose tissue (VAT) and subcutaneous adipose tissue, bone and fat biomarkers were evaluated in 120 healthy men aged ≥ 60 years. Indians had higher BMD values compared to Chinese at the lumbar spine (β = 20.336, SE = 4.749, p < 0.001) and the femoral neck (e β  = 1.105, SE = 0.032, p < 0.001), after adjusting for BTMs, fat composition and lifestyle choices. Marrow fat, VAT and adiponectin were independent predictors of BMD. However, these factors did not explain the lower BMD observed in older Chinese men. Our findings suggest that older Chinese men are at significant risk of osteoporotic fractures due to lower BMD. Fat appears to be a key factor associated with lower BMD, and warrants further longitudinal studies to elucidate the complex interactions between adipose tissue and bone strength.

Increased Epicardial Adipose Tissue Volume in HIV-Infected Men and Relationships to Body Composition and Metabolic Parameters

PubMed Central

Lo, Janet; Abbara, Suhny; Rocha-Filho, Jose A.; Shturman, Leon; Wei, Jeffrey; Grinspoon, Steven K.

2011-01-01

Summary Epicardial fat accumulation may have important clinical consequences, yet little is known regarding this depot in HIV patients. We compared epicardial fat volume in 78 HIV-infected men and 32 HIV-negative controls. Epicardial fat volume was higher in HIV than control subjects (p=0.04). In HIV patients, epicardial fat volume was strongly associated with visceral adipose tissue area (VAT)(ρ = 0.76, p<0.0001), fasting glucose (ρ = 0.41, p=0.001) and insulin (ρ = 0.44, p=0.0003). Relationships with glucose and insulin remained significant controlling for age, race, BMI, adiponectin, VAT, and antiretroviral therapy. Epicardial fat may be an important fat depot in HIV-infected patients. PMID:20588167

Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women.

PubMed

Dozio, Elena; Briganti, Silvia; Delnevo, Alessandra; Vianello, Elena; Ermetici, Federica; Secchi, Francesco; Sardanelli, Francesco; Morricone, Lelio; Malavazos, Alexis E; Corsi Romanelli, Massimiliano M

2017-12-01

Soluble receptor for advanced glycation end products (sRAGE) is a decoy receptor which sequesters RAGE ligands and acts as a cytoprotective agent. To date, it is unclear whether the lower sRAGE levels observed in obesity are a marker of increased overall adiposity or reflect increases in particular fat depots. Therefore, we evaluated in healthy women the relationship among sRAGE and indicators of adiposity, including abdominal visceral (VAT) and epicardial visceral (EAT) adipose tissues, to explore the potential role of sRAGE as an earlier biomarker of cardiometabolic risk. Plasma sRAGE levels were quantified by an enzyme-linked immunosorbent assay in 47 healthy women. Total fat mass (FM) and fat-free mass were estimated with bioimpedance analysis. Anthropometric measures and biochemical data were recorded. Subcutaneous adipose tissue, VAT and EAT volumes were measured by magnetic resonance imaging. Obese women had lower sRAGE levels compared to normal-weight women. sRAGE levels were also lower in women with a waist circumference (WC) larger than 80 cm. Correlation analyses indicated an inverse association of sRAGE with body mass index and FM. Concerning adipose tissue distribution, sRAGE inversely correlated with WC, EAT and VAT depots. In a multiple stepwise regression analysis, performed to emphasize the role of fat distribution, EAT volume was the only predictor of sRAGE. Lower sRAGE levels reflect accumulation of visceral fat mainly at the epicardial level and are present in advance of metabolic complications in adult women. sRAGE quantification might be an early marker of cardiometabolic risk.

PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity.

PubMed

Huang, Zhi Hua; Manickam, Buvana; Ryvkin, Victoria; Zhou, Xiaohong Joe; Fantuzzi, Giamila; Mazzone, Theodore; Sam, Susan

2013-01-01

Adipose tissue macrophage (ATM) infiltration is a major pathway for obesity-induced insulin resistance but has not been studied as a mechanism for insulin resistance in PCOS. We tested whether polycystic ovary syndrome (PCOS) is associated with increased ATM infiltration, especially of inflammatory subtype identified by the CD11c marker. We conducted a case-control study at an academic medical center in the United States. Fourteen PCOS and 14 control women of similar age and body mass index (BMI) underwent a gluteal fat biopsy. Markers of ATM, integrins, TNF-α, and adiponectin, were analyzed by quantitative RT-PCR using a standard curve method. Crown-like structures (CLS) were identified by immunohistochemistry. Abdominal magnetic resonance imaging and frequently sampled i.v. glucose tolerance test were performed to assess abdominal fat and insulin sensitivity (SI). Women with PCOS were compared with control women of similar age and BMI for ATM markers, CLS density, adipose tissue expression of inflammatory cytokines and adiponectin, SI, and abdominal fat depots. Women with PCOS had an increase in CD11c expression (P = 0.03), CLS density (P = 0.001), α5 expression (P = 0.009), borderline increase in TNF-α expression (P = 0.08), and a decrease in adiponectin expression (P = 0.02) in gluteal adipose tissue. Visceral (P = 0.009) and sc abdominal fat (P = 0.005) were increased in PCOS. SI was lower in PCOS (P = 0.008). PCOS is associated with an increase in CD11c expression and CLS density and a decrease in adiponectin expression in sc adipose tissue. Additionally, PCOS is associated with higher central abdominal fat depots independent of BMI. These alterations are present among mostly nonobese women and could represent mechanisms for insulin resistance.

Magnetic Resonance Imaging Cooling-Reheating Protocol Indicates Decreased Fat Fraction via Lipid Consumption in Suspected Brown Adipose Tissue

PubMed Central

Lundström, Elin; Strand, Robin; Johansson, Lars; Bergsten, Peter; Ahlström, Håkan; Kullberg, Joel

2015-01-01

Objectives To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure. Materials and Methods Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related). Results sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure). Conclusions The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion. PMID:25928226

Magnetic resonance imaging cooling-reheating protocol indicates decreased fat fraction via lipid consumption in suspected brown adipose tissue.

PubMed

Lundström, Elin; Strand, Robin; Johansson, Lars; Bergsten, Peter; Ahlström, Håkan; Kullberg, Joel

2015-01-01

To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure. Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R2*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R2* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related). sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R2* tended to increase (mean = 0.65 s-1, P = 0.051) and SAT-R2* increased (mean = 0.40 s-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure). The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.

Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue.

PubMed

Fusaru, Ana Marina; Stănciulescu, Camelia Elena; Surlin, V; Taisescu, C; Bold, Adriana; Pop, O T; Baniţă, Ileana Monica; Crăiţoiu, Stefania; Pisoschi, Cătălina Gabriela

2012-01-01

White adipose tissue from different locations is characterized by significant differences in the structure of adipocyte "secretoma". Fat accumulation in the central-visceral depots is usually associated with a chronic inflammatory state, which is complicated by the metabolic syndrome. Recently, the adipose tissue was emerged to have an essential role in the innate immunity, adipocytes being considered effector cells due to the presence of the Toll-like receptors (TLRs). In this study, we compared the expression of TNF-α, TLR2 and TLR4 in peripheral-subcutaneous and central-peritoneal adipose depots in three different conditions - lean, obese and obese diabetic - using immunohistochemistry. Our results suggest a correlation between the incidence of the stromal vascular cells and adipocytes TNF-α and TLR4 in the visceral depots in strong correlation with adipose tissue expansion. TLR2 positive cells were seen in the peripheral depots from all groups without any association with fat accumulation. These results focus on the existence of a new pathogenic pathway, the activation of TLR4, for the involvement of visceral adipose tissue in the activation and maintenance of the inflammatory cascade in obesity.

Uncultivated stromal vascular fraction is equivalent to adipose-derived stem and stromal cells on porous polyurethrane scaffolds forming adipose tissue in vivo.

PubMed

Griessl, Michael; Buchberger, Anna-Maria; Regn, Sybille; Kreutzer, Kilian; Storck, Katharina

2018-06-01

To find an alternative approach to contemporary techniques in tissue augmentation and reconstruction, tissue engineering strategies aim to involve adipose-derived stem and stromal cells (ASCs) harboring a strong differentiation potential into various tissue types such as bone, cartilage, and fat. Animal research. The stromal vascular fraction (SVF) was used directly as a cell source to provide a potential alternative to contemporary ASC-based adipose tissue engineering. Seeded in TissuCol fibrin, we applied ASCs or SVF cells to porous, degradable polyurethane (PU) scaffolds. We successfully demonstrated the in vivo generation of volume-stable, well-vascularized PU-based constructs containing host-derived mature fat pads. Seeded human stem cells served as modulators of host-cell migration rather than differentiating themselves. We further demonstrated that preliminary culture of SVF cells was not necessary. Our results bring adipose tissue engineering, together with automated processing devices, closer to clinical applicability. The time-consuming and cost-intensive culture and induction of the ASCs is not necessary. NA. Laryngoscope, 128:E206-E213, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

An increase in epicardial fat in women is associated with thrombotic risk.

PubMed

Basurto Acevedo, Lourdes; Barrera Hernández, Susana; Fernández Muñoz, María de Jesús; Saucedo García, Renata Patricia; Rodríguez Luna, Ana Karen; Martínez Murillo, Carlos

2018-01-29

A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r=0.475, P=.001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat.

PubMed

Kazak, Lawrence; Chouchani, Edward T; Jedrychowski, Mark P; Erickson, Brian K; Shinoda, Kosaku; Cohen, Paul; Vetrivelan, Ramalingam; Lu, Gina Z; Laznik-Bogoslavski, Dina; Hasenfuss, Sebastian C; Kajimura, Shingo; Gygi, Steve P; Spiegelman, Bruce M

2015-10-22

Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PAPERCLIP. Copyright © 2015 Elsevier Inc. All rights reserved.

Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for 'sick fat' and metabolic disease.

PubMed

Bays, Harold E

2009-11-01

Agonists of 5-hydroxytryptamine (5-HT; serotonin) receptors promote loss of excessive body fat (adiposity) and improve metabolic parameters associated with adiposity-induced adipose tissue dysfunction (adiposopathy or 'sick fat'). By improving adipose tissue pathogenic endocrine and immune responses in overweight patients, 5-HT receptor agonists may improve metabolic disease. Lorcaserin (APD-356) is a selective 5-HT2c receptor agonist that promotes weight loss. Probably owing to its selectivity for the 5-HT2c receptor, clinical trial evidence supports that lorcaserin does not adversely affect heart valves or pulmonary artery pressure. This review examines: the mechanisms by which serotonergic pathways improve adiposity and adiposopathy; historical data and perspective regarding the efficacy and safety of prior 5-HT agonists; speculation regarding future paradigms in treating adiposopathy; and why lorcaserin may prove to be a safe and generally well-tolerated agent that not only improves the weight of patients, but also improves the health of patients.

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.

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period.

PubMed

Saleh, J; Summers, L K; Cianflone, K; Fielding, B A; Sniderman, A D; Frayn, K N

1998-04-01

The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominent until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.

Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

PubMed

Jankowski, Marek; Gawrych, Mariusz; Adamska, Urszula; Ciescinski, Jakub; Serafin, Zbigniew; Czajkowski, Rafal

2017-02-01

Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin.

Relationship of Adipocyte Size with Adiposity and Metabolic Risk Factors in Asian Indians

PubMed Central

Meena, Ved Prakash; Seenu, V.; Sharma, M. C.; Mallick, Saumya Ranjan; Bhalla, Ashu Seith; Gupta, Nandita; Mohan, Anant; Guleria, Randeep; Pandey, Ravindra M.; Luthra, Kalpana; Vikram, Naval K.

2014-01-01

Background Enlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions. Objectives We evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians. Methodology Eighty (40 males and 40 females) non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L2–3 level (computed tomography) and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP). During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination. Results Females had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF), total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR), the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity. Conclusion Omental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity. PMID:25251402

Effect of Sea-Buckthorn (Hippophaë rhamnoides L.) Pulp Oil Consumption on Fatty Acids and Vitamin A and E Accumulation in Adipose Tissue and Liver of Rats.

PubMed

Czaplicki, Sylwester; Ogrodowska, Dorota; Zadernowski, Ryszard; Konopka, Iwona

2017-06-01

An in vivo experiment was conducted to determine the effect of sea-buckthorn pulp oil feeding on the fatty acid composition of liver and adipose tissue of Wistar rats and the liver accumulation of retinol, its esters and α-tocopherol. For a period of 28 days, rats were given a modified casein diet (AIN-93) in which sea-buckthorn pulp oil, soybean oil and pork lard were used as sources of fat. Compared to the other fat sources, sea-buckthorn pulp oil was the most abundant in C16 fatty acids, carotenoids (mainly β-carotene) and tocopherols (mainly α-tocopherol). Its consumption was reflected in an increased share of palmitoleic acid in adipose tissue and the liver and an increased level of retinol in liver tissues (this was not observed for its esters). Although the type of fat did not have a significant effect on the average content of α-tocopherol in the liver, the variation of saturation of this tissue with α-tocopherol was the lowest when rats were fed a diet containing sea-buckthorn oil. This experiment indicates the possibility of affecting adipose tissue and liver by a diet.

Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

PubMed Central

Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

2012-01-01

We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction.

PubMed

Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J; Liaw, Lucy

2012-09-28

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

TRPV1 agonist monoacylglycerol increases UCP1 content in brown adipose tissue and suppresses accumulation of visceral fat in mice fed a high-fat and high-sucrose diet.

PubMed

Iwasaki, Yusaku; Tamura, Yasuko; Inayoshi, Kimiko; Narukawa, Masataka; Kobata, Kenji; Chiba, Hiroshige; Muraki, Etsuko; Tsunoda, Nobuyo; Watanabe, Tatsuo

2011-01-01

The administration of such a transient receptor potential vanilloid 1 (TRPV1) agonist as capsaicin, which is a pungent ingredient of red pepper, promotes energy metabolism and suppresses visceral fat accumulation. We have recently identified monoacylglycerols (MGs) having an unsaturated long-chain fatty acid as the novel TRPV1 agonist in foods. We investigated in this present study the effects of dietary MGs on uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT) and on fat accumulation in mice fed with a high-fat, high-sucrose diet. The MG30 diet that substituted 30% of all lipids for MGs (a mixture of 1-oleoylglycerol, 1-linoleoylglycerol and 1-linolenoylglycerol) significantly increased the UCP1 content of IBAT and decreased the weight of epididymal white adipose tissue, and the serum glucose, total cholesterol and free fatty acid levels. The diet containing only 1-oleoylglycerol as MG also increased UCP1 expression in IBAT. MGs that activated TRPV1 also therefore induced the expression of UCP 1 and prevented visceral fat accumulation as well as capsaicin.

The Associations between Adiposity, Cognitive Function, and Achievement in Children.

PubMed

Raine, Lauren; Drollette, Eric; Kao, Shih-Chun; Westfall, Daniel; Chaddock-Heyman, Laura; Kramer, Arthur F; Khan, Naiman; Hillman, Charles

2018-04-27

Although obesity has been related to measures of academic achievement and cognition in children, the influence of fat distribution, specifically visceral adiposity, on select aspects of achievement and cognitive function remains poorly characterized among preadolescent children. The aim of this study was to evaluate the relation of adiposity, particularly visceral adipose tissue, on achievement and cognitive function among children. Children with obesity (ages 7-9 years old, N= 55, 35 females) completed cognitive and academic tests. Normal weight children (N= 55, 35 females) were matched to this group on demographic characteristics and aerobic fitness. Covariate analyses included age, Brief Intellectual Ability (BIA), SES, and fat free VO2 (VO2 peak adjusted for lean mass; ml/kg lean/min). Adiposity (i.e., whole body percent fat, subcutaneous abdominal adipose tissue (SAAT), and visceral adipose tissue (VAT)) was assessed using dual energy X-ray absorptiometry. The results of this study revealed that, relative to their normal weight counterparts, children with obesity had significantly lower performance on tests of reading and math. Analyses revealed that among children with obesity, %Fat and SAAT were not related to cognitive abilities. However, higher VAT was associated with poorer intellectual abilities, p's≤0.04; and cognitive performance (i.e. Thinking Ability and Cognitive Efficiency), p's≤0.04. However, among normal weight children, VAT was positively associated with intellectual abilities and cognitive efficiency. In conclusion, the results suggest that VAT was selectively and negatively related with cognition among children with obesity. Along with the dangerous metabolic nature of VAT, its detrimental relationship with obese children's intellectual and cognitive functioning is concerning.

Predictors for cecal insertion time: the impact of abdominal visceral fat measured by computed tomography.

PubMed

Nagata, Naoyoshi; Sakamoto, Kayo; Arai, Tomohiro; Niikura, Ryota; Shimbo, Takuro; Shinozaki, Masafumi; Noda, Mitsuhiko; Uemura, Naomi

2014-10-01

Several factors affect the risk for longer cecal insertion time. The aim of this study was to identify the predictors of longer insertion time and to evaluate the effect of visceral fat measured by CT. This is a retrospective observational study. Outpatients for colorectal cancer screening who underwent colonoscopies and CT were enrolled. Computed tomography was performed in individuals who requested cancer screening and in those with GI bleeding. Information on obesity indices (BMI, visceral adipose tissue, and subcutaneous adipose tissue area), constipation score, history of abdominal surgery, poor preparation, fellow involvement, diverticulosis, patient discomfort, and the amount of sedation used was collected. The cecal insertion rate was 95.2% (899/944), and 899 patients were analyzed. Multiple regression analysis showed that female sex, lower BMI, lower visceral adipose tissue area, lower subcutaneous adipose tissue area, higher constipation score, history of surgery, poor bowel preparation, and fellow involvement were independently associated with longer insertion time. When obesity indices were considered simultaneously, smaller subcutaneous adipose tissue area (p = 0.038), but not lower BMI (p = 0.802) or smaller visceral adipose tissue area (p = 0.856), was associated with longer insertion time; the other aforementioned factors remained associated with longer insertion time. In the subanalysis of normal-weight patients (BMI <25 kg/m), a smaller subcutaneous adipose tissue area (p = 0.002), but not a lower BMI (p = 0.782), was independently associated with a longer insertion time. Longer insertion time had a positive correlation with a higher patient discomfort score (ρ = 0.51, p < 0.001) and a greater amount of midazolam use (ρ = 0.32, p < 0.001). This single-center retrospective study includes a potential selection bias. In addition to BMI and intra-abdominal fat, female sex, constipation, history of abdominal surgery, poor preparation, and fellow involvement were predictors of longer cecal insertion time. Among the obesity indices, high subcutaneous fat accumulation was the best predictive factor for easier passage of the colonoscope, even when body weight was normal.

Beta-arrestin-1 protein represses diet-induced obesity.

PubMed

Zhuang, Le-nan; Hu, Wen-xiang; Zhang, Ming-liang; Xin, Shun-mei; Jia, Wei-ping; Zhao, Jian; Pei, Gang

2011-08-12

Diet-related obesity is a major metabolic disorder. Excessive fat mass is associated with type 2 diabetes, hepatic steatosis, and arteriosclerosis. Dysregulation of lipid metabolism and adipose tissue function contributes to diet-induced obesity. Here, we report that β-arrestin-1 knock-out mice are susceptible to diet-induced obesity. Knock-out of the gene encoding β-arrestin-1 caused increased fat mass accumulation and decreased whole-body insulin sensitivity in mice fed a high-fat diet. In β-arrestin-1 knock-out mice, we observed disrupted food intake and energy expenditure and increased macrophage infiltration in white adipose tissue. At the molecular level, β-arrestin-1 deficiency affected the expression of many lipid metabolic genes and inflammatory genes in adipose tissue. Consistently, transgenic overexpression of β-arrestin-1 repressed diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that β-arrestin-1 plays a role in metabolism regulation.

Trafficking of dietary fat in lean rats.

PubMed

Bessesen, D H; Rupp, C L; Eckel, R H

1995-03-01

Despite increasing interest in the role that fuel partitioning plays in determining body composition, the relative importance of oxidative versus storage pathways in the clearance of dietary fat remains unclear. A widely held view is that the primary destination of chylomicron triglyceride fatty acids (TGFA) is adipose tissue, and the primary source of lipid fuel for skeletal muscle is non-esterified fatty acids (NEFA). An alternate view is that muscle, not adipose tissue, is the primary site of TGFA clearance. This view is supported by estimates of the total lipoprotein lipase content of muscle and adipose tissue. To directly study the partitioning of dietary fat between oxidation and storage, 14C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic rate followed over 30 days. Two hours after ingestion, more than 3.5 times as much label was found in skeletal muscle tissue (2.42 +/- 0.45 nmols) and CO2 (0.25 +/- 0.01 nmols) than was found in adipose tissue (0.71 +/- 0.14 nmols). Intramuscular triglyceride was the lipid class most extensively labeled. After skeletal muscle, liver was the next most important site of TGFA clearance. Surprisingly a substantial quantity of label remained associated with the GI tract even 24 hours after ingestion. Between 2 and 10 days following ingestion there was a net decline in the 14C content of muscle, liver and GI tract, associated with a net rise in the 14C content of adipose tissue. These findings demonstrate: 1) the importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the importance of intramuscular partitioning of lipid fuels between direct oxidation and storage as TG, 3) the potentially important role of the GI tract in the delivery of dietary fat to the circulation 10-24 hours following ingestion, and 4) the stability of adipose tissue as a storage site. The complex nature of the tissue-specific clearance of TGFA over time is perhaps better described by the term "trafficking" than by the more commonly used term "partitioning." Future studies of TGFA clearance combined with sampling of relevant tissues over time will provide insight into the specific roles that abnormalities in liver, muscle and adipose tissue TGFA metabolism play in the development of hypertriglyceridemic disorders and states of increased or reduced body weight.

Ectopic fat is linked to prior cardiovascular events in men with HIV.

PubMed

Orlando, Gabriella; Gabriella, Orlando; Guaraldi, Giovanni; Giovanni, Guaraldi; Zona, Stefano; Stefano, Zona; Carli, Federica; Federica, Carli; Bagni, Pietro; Pietro, Bagni; Menozzi, Marianna; Marianna, Menozzi; Cocchi, Stefania; Stefania, Cocchi; Scaglioni, Riccardo; Riccardo, Scaglioni; Ligabue, Guido; Guido, Ligabue; Raggi, Paolo; Paolo, Raggi

2012-04-15

Epicardial Adipose Tissue (EAT) has been associated with adverse cardiovascular events in the general population. We studied the association of general adiposity measures (body mass index, waist circumference) and ectopic adipose tissue [visceral adipose tissue (VAT); liver fat (LF); EAT) with prevalent cardiovascular disease (CVD) (prior myocardial infarction, coronary revascularization, stroke, peripheral vascular disease] in 583 HIV-infected men. VAT, EAT, and LF (liver/spleen attenuation ratio < 1.1) were measured by computed tomography. Patients' mean age was 48.5 ± 8.1 years, prior CVD was present in 33 (5.7%) patients. Factors independently associated with CVD on multivariable analyses were age [incidence-rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.02 to 1.12], smoking (IRR = 2.70, 95% CI: 1.22 to 6.01), Center for Disease Control group C (IRR = 3.09, 95% CI: 1.41 to 6.76), EAT (IRR = 1.13, 95% CI: 1.04 to 1.24, per 10 cm), LF (IRR = 1.17, 95% CI: 1.04 to 1.32), and VAT (IRR = 1.05, 95% CI: 1.00 to 1.10, per 10 cm). Ectopic fat but not general adiposity measures were associated with prevalent CVD in men with HIV.

Metabolic and Structural Effects of Phosphatidylcholine and Deoxycholate Injections on Subcutaneous Fat

PubMed Central

Reeds, Dominic N.; Mohammed, B. Selma; Klein, Samuel; Boswell, Craig Brian

2013-01-01

Background: Phosphatidylcholine and deoxycholate (PC-DC) injections are a popular nonsurgical method to eliminate unwanted fat. The safety and efficacy of this approach is uncertain. Objective: The authors evaluate the effects of PC-DC treatments on body composition, adipocyte function, and mechanisms responsible for fat loss. Methods: This randomized, open-label study enrolled 13 women with a body mass index (BMI) ≤30 kg/m2 and lower abdominal subcutaneous fat suitable for small-volume liposuction. Patients were randomized by the final digit of their Social Security numbers and received between 2 and 4 PC-DC treatments, spaced 8 weeks apart. One side below the umbilicus was injected with PC-DC. The contralateral, control side received no treatment. Adipose tissue biopsies were performed on the treated side at baseline, 1 week after the first treatment, and 8 weeks after the final treatment. The primary outcome was change in adipose tissue thickness at baseline and 8 weeks after the final treatment. Results: Seven women completed the study. Treatment with PC-DC significantly reduced the thickness of the anterior subcutaneous abdominal fat (P = .004). Adipose tissue showed rapid increases in crown-like structures, macrophage infiltration, and reduced expression of leptin, hormone-sensitive lipase, adipose tissue triglyceride lipase, and CD36. Plasma C-reactive protein, lipid profile, and plasma glucose concentrations were unchanged. Conclusions: PC-DC injections can effectively reduce abdominal fat volume and thickness by inducing adipocyte necrosis. These treatments do not appear to increase circulating markers of inflammation or affect glucose and lipid metabolism. Level of Evidence: 3 PMID:23439063

A correlation between the weight of visceral adipose tissue and selected anthropometric indices: an autopsy study.

PubMed

Edston, E

2013-06-01

Several anthropometric indices are used as an estimation of the true amount of body fat, e.g. the body mass index (BMI). These indices correlate well with each other and with non-invasive measurements of total body fat and visceral adipose tissue. The indices generally show a strong correlation with cardiovascular disease and diabetes mellitus. Direct measurement of visceral adipose tissue by weight (VAW) from autopsy cases positively correlates with the anthropometric indices. VAW also positively correlates with fatty tissue thickness at separate locations, i.e. renal capsular and epicardial fatty tissue. VAW is positively correlated with the severity of cardiosclerosis and diabetes mellitus, but there is no significant difference in VAW between deaths from cardiovascular complications and other natural deaths. Different anthropometric indices and non-invasive methods have been used to estimate the total burden of body fat. Increased visceral adipose tissue is believed to involve elevated risk for cardiovascular disease, type 2 diabetes, chronic kidney disease and hypertension. At present, the optimal method to estimate the visceral and total amount of fat remains undecided. In the present study of 201 autopsy cases, direct measurement of visceral adipose tissue by weight (VAW) has been compared to common anthropometric indices, namely body mass index (BMI), waist-to-hip ratio (W/Hip ratio), waist-to-height ratio (W/Height ratio), body adiposity index (BAI), waist circumference and abdominal wall thickness. The prevalence and severity of cardiovascular disease, diabetes mellitus and cause of death were also correlated with the anthropometric data. The outcome was that all anthropometric measurements showed a significant positive correlation with the weight of visceral adipose tissue, and the r-value of the comparison to waist circumference was the highest (r = 0.82). Thickness of fatty tissue enveloping the kidneys and heart, as well as heart weight, was also strongly correlated with VAW. VAW was significantly higher in men compared with women, and in diabetes mellitus compared with non-diabetic patients. VAW was also positively correlated with the severity of coronary artery sclerosis. On the contrary, there was no significant difference between high and low VAW comparing between deaths from cardiovascular complications and natural deaths from other causes. The conclusion is that the anthropometric measurements give a good approximation of the real amount of visceral fat, and that waist circumference and W/Height ratio show the best correlations. © 2013 The Author. Clinical Obesity © 2013 International Association for the Study of Obesity.

Stimulation of S14 mRNA and lipogenesis in brown fat by hypothyroidism, cold exposure, and cafeteria feeding: evidence supporting a general role for S14 in lipogenesis and lipogenesis in the maintenance of thermogenesis

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

Freake, H.C.; Oppenheimer, J.H.

1987-05-01

In liver, thyroid hormone rapidly induces S14 mRNA, which encodes a small acidic protein. This sequence is abundantly expressed only in lipogenic tissues and is thought to have some function in fat metabolism. In the euthyroid rat, we measured 20-fold higher levels of S14 mRNA in interscapular brown adipose tissue than liver. Furthermore, whereas in liver or epididymal fat, hypothyroidism resulted in an 80% fall in S14 mRNA, in brown fat the level of this sequence increased a further 3-fold. In all three tissues, the expression of S14 mRNA correlated well with lipogenesis, as assessed by /sup 3/H/sub 2/O incorporation.more » Physiological activation of brown fat by chronic cold exposure or cafeteria feeding increased the concentration of S14 mRNA in this tissue and again this was accompanied by a greater rate of fatty acid synthesis. Overall, in liver and white and brown adipose tissue, S14 mRNA and lipogenesis were well correlated and strongly suggest a function of the S14 protein related to fat synthesis. These studies suggest that the S14 protein and lipogenesis may be important for thyroid hormone-induced and brown adipose tissue thermogenesis and that stimulation of these functions in hypothyroid brown fat is a consequence of decreased thyroid hormone-induced thermogenesis elsewhere.« less

Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: The Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Different aspects of diet may be differentially related to body fat distribution. The purpose of this study was to assess associations between whole- and refined- grain intake and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). We examined the cross-sectional associati...

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

Allele compensation in tip60+/- mice rescues white adipose tissue function in vivo.

PubMed

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/- mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/- mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/- displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/- mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice.

Inhibition of intestinal cholesterol absorption decreases atherosclerosis but not adipose tissue inflammation

PubMed Central

Umemoto, Tomio; Subramanian, Savitha; Ding, Yilei; Goodspeed, Leela; Wang, Shari; Han, Chang Yeop; Teresa, Antonio Sta.; Kim, Jinkyu; O'Brien, Kevin D.; Chait, Alan

2012-01-01

Adipose tissue inflammation is associated with insulin resistance and increased cardiovascular disease risk in obesity. We previously showed that addition of cholesterol to a diet rich in saturated fat and refined carbohydrate significantly worsens dyslipidemia, insulin resistance, adipose tissue macrophage accumulation, systemic inflammation, and atherosclerosis in LDL receptor-deficient (Ldlr−/−) mice. To test whether inhibition of intestinal cholesterol absorption would improve metabolic abnormalities and adipose tissue inflammation in obesity, we administered ezetimibe, a dietary and endogenous cholesterol absorption inhibitor, to Ldlr−/− mice fed chow or high-fat, high-sucrose (HFHS) diets without or with 0.15% cholesterol (HFHS+C). Ezetimibe blunted weight gain and markedly reduced plasma lipids in the HFHS+C group. Ezetimibe had no effect on glucose homeostasis or visceral adipose tissue macrophage gene expression in the HFHS+C fed mice, although circulating inflammatory markers serum amyloid A (SSA) and serum amyloid P (SSP) levels decreased. Nevertheless, ezetimibe treatment led to a striking (>85%) reduction in atherosclerotic lesion area with reduced lesion lipid and macrophage content in the HFHS+C group. Thus, in the presence of dietary cholesterol, ezetimibe did not improve adipose tissue inflammation in obese Ldlr−/− mice, but it led to a major reduction in atherosclerotic lesions associated with improved plasma lipids and lipoproteins. PMID:22956784

Exploratory Studies on Biomarkers: An Example Study on Brown Adipose Tissue

NASA Astrophysics Data System (ADS)

Watanabe, Masahiro; Yamazaki, Naoshi; Kataoka, Masatoshi; Shinohara, Yasuo

In mammals, two kinds of adipose tissue are known to exist, i.e., white (WAT) and brown (BAT) adipose tissue. The physiological role of WAT is storage of excess energy as fat, whereas that of BAT is the expenditure of excess energy as heat. The uncoupling protein UCP1, which is specifically expressed in brown fat mitochondria, dissipates the proton electrochemical potential across the inner mitochondrial membrane, known as a driving force of ATP synthesis, and thus it dissipates excess energy in a form of heat. Because deficiency in effective expenditure of excess energy causes accumulation of this energy in the form of fat (i.e., obesity), it is very important to understand the energy metabolism in this tissue for the development of anti-obesity drugs. In this article, in addition to providing a brief introduction to the functional properties of BAT and UCP1, the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

PubMed

Kir, Serkan; Komaba, Hirotaka; Garcia, Ana P; Economopoulos, Konstantinos P; Liu, Wei; Lanske, Beate; Hodin, Richard A; Spiegelman, Bruce M

2016-02-09

Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.

Green tea extract supplementation induces the lipolytic pathway, attenuates obesity, and reduces low-grade inflammation in mice fed a high-fat diet.

PubMed

Cunha, Cláudio A; Lira, Fábio S; Rosa Neto, José C; Pimentel, Gustavo D; Souza, Gabriel I H; da Silva, Camila Morais Gonçalves; de Souza, Cláudio T; Ribeiro, Eliane B; Sawaya, Alexandra Christine Helena Frankland; Oller do Nascimento, Cláudia M; Rodrigues, Bruno; de Oliveira Carvalho, Patrícia; Oyama, Lila M

2013-01-01

The aim of this study was to evaluate the effects of green tea Camellia sinensis extract on proinflammatory molecules and lipolytic protein levels in adipose tissue of diet-induced obese mice. Animals were randomized into four groups: CW (chow diet and water); CG (chow diet and water + green tea extract); HW (high-fat diet and water); HG (high-fat diet and water + green tea extract). The mice were fed ad libitum with chow or high-fat diet and concomitantly supplemented (oral gavage) with 400 mg/kg body weight/day of green tea extract (CG and HG, resp.). The treatments were performed for eight weeks. UPLC showed that in 10 mg/mL green tea extract, there were 15 μg/mg epigallocatechin, 95 μg/mg epigallocatechin gallate, 20.8 μg/mg epicatechin gallate, and 4.9 μg/mg gallocatechin gallate. Green tea administered concomitantly with a high-fat diet increased HSL, ABHD5, and perilipin in mesenteric adipose tissue, and this was associated with reduced body weight and adipose tissue gain. Further, we observed that green tea supplementation reduced inflammatory cytokine TNFα levels, as well as TLR4, MYD88, and TRAF6 proinflammatory signalling. Our results show that green tea increases the lipolytic pathway and reduces adipose tissue, and this may explain the attenuation of low-grade inflammation in obese mice.

An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice.

PubMed

Wijayatunga, Nadeeja N; Pahlavani, Mandana; Kalupahana, Nishan S; Kottapalli, Kameswara Rao; Gunaratne, Preethi H; Coarfa, Cristian; Ramalingam, Latha; Moustaid-Moussa, Naima

2018-02-06

Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.

Novel Insights into the Relationship between Diabetes and Osteoporosis

PubMed Central

de Paula, Francisco J. A.; Horowitz, Mark C.; Rosen, Clifford J.

2012-01-01

Only three decades ago adipose tissue was considered inert with little relationship to insulin resistance. Similarly bone has long been thought purely in its structural context. In the last decade, emerging evidence has revealed important endocrine roles for both bone and adipose tissue. The interaction between these two tissues is remarkable. Bone marrow mesenchymal stem cells give rise to both osteoblasts and adipocytes. Leptin and adiponectin, two adipokines secreted by fat tissue, control energy homeostasis, but also have complex actions on the skeleton. In turn, the activities of bone cells are not limited to their bone remodeling activities, but also to modulation of adipose sensitivity and insulin secretion. This review will discuss these new insights linking bone remodeling to the control of fat metabolism and the association between diabetes mellitus and osteoporosis. PMID:20938995

Validation of Anthropometric Indices of Adiposity against Whole-Body Magnetic Resonance Imaging – A Study within the German European Prospective Investigation into Cancer and Nutrition (EPIC) Cohorts

PubMed Central

Neamat-Allah, Jasmine; Wald, Diana; Hüsing, Anika; Teucher, Birgit; Wendt, Andrea; Delorme, Stefan; Dinkel, Julien; Vigl, Matthaeus; Bergmann, Manuela M.; Feller, Silke; Hierholzer, Johannes; Boeing, Heiner; Kaaks, Rudolf

2014-01-01

Background In epidemiological studies, measures of body fat generally are obtained through anthropometric indices such as the body mass index (BMI), waist (WC), and hip circumferences (HC). Such indices, however, can only provide estimates of a person’s true body fat content, overall or by adipose compartment, and may have limited accuracy, especially for the visceral adipose compartment (VAT). Objective To determine the extent to which different body adipose tissue compartments are adequately predicted by anthropometry, and to identify anthropometric measures alone, or in combination to predict overall adiposity and specific adipose tissue compartments, independently of age and body size (height). Methods In a sub-study of 1,192 participants of the German EPIC (European Prospective Investigation into Cancer and Nutrition) cohorts, whole-body MRI was performed to determine adipose and muscle tissue compartments. Additional anthropometric measurements of BMI, WC and HC were taken. Results After adjusting for age and height, BMI, WC and HC were better predictors of total body volume (TBV), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) than for VAT, coronary adipose tissue (CAT) and skeletal muscle tissue (SMT). In both sexes, BMI was the best predictor for TBV (men: r = 0.72 [0.68–0.76], women: r = 0.80 [0.77–0.83]) and SMT (men: r = 0.52 [0.45–0.57], women: r = 0.48 [0.41–0.54]). WC was the best predictor variable for TAT (r = 0.48 [0.41–0.54]), VAT (r = 0.44 [0.37–0.50]) and CAT (r = 0.34 [0.26–0.41]) (men), and for VAT (r = 0.42 [0.35–0.49]) and CAT (r = 0.29 [0.22–0.37]) (women). BMI was the best predictor for TAT (r = 0.49 [0.43–0.55]) (women). HC was the best predictor for SAT (men (r = 0.39 [0.32–0.45]) and women (r = 0.52 [0.46–0.58])). Conclusions Especially the volumes of internal body fat compartments are poorly predicted by anthropometry. A possible implication may be that associations of chronic disease risks with the sizes of internal body fat as measured by BMI, WC and HC may be strongly underestimated. PMID:24626110

Apolipoprotein CIII overexpression exacerbates diet-induced obesity due to adipose tissue higher exogenous lipid uptake and retention and lower lipolysis rates.

PubMed

Raposo, Helena F; Paiva, Adriene A; Kato, Larissa S; de Oliveira, Helena C F

2015-01-01

Hypertriglyceridemia is a common type of dyslipidemia found in obesity. However, it is not established whether primary hyperlipidemia can predispose to obesity. Evidences have suggested that proteins primarily related to plasma lipoprotein transport, such as apolipoprotein (apo) CIII and E, may significantly affect the process of body fat accumulation. We have previously observed an increased adiposity in response to a high fat diet (HFD) in mice overexpressing apoCIII. Here, we examined the potential mechanisms involved in this exacerbated response of apoCIII mice to the HFD. We measured body energy balance, tissue capacity to store exogenous lipids, lipogenesis and lipolysis rates in non-transgenic and apoCIII overexpressing mice fed a HFD during two months. Food intake, fat excretion and whole body CO2 production were similar in both groups. However, the adipose tissue mass (45 %) and leptin plasma levels (2-fold) were significantly greater in apoCIII mice. Lipogenesis rates were similar, while exogenous lipid retention was increased in perigonadal (2-fold) and brown adipose tissues (40 %) of apoCIII mice. In addition, adipocyte basal lipolysis (55 %) and in vivo lipolysis index (30 %) were significantly decreased in apoCIII mice. A fat tolerance test evidenced delayed plasma triglyceride clearance and greater transient availability of non-esterified fatty acids (NEFA) during the post-prandial state in the apoCIII mice plasma. Thus, apoCIII overexpression resulted in increased NEFA availability to adipose uptake and decreased adipocyte lipolysis, favoring lipid enlargement of adipose depots. We propose that plasma apoCIII levels represent a new risk factor for diet-induced obesity.

Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice.

PubMed

Sun, Quancai; Xiao, Xiao; Kim, Yoo; Kim, Daeyoung; Yoon, Kyoon Sup; Clark, John M; Park, Yeonhwa

2016-12-14

Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice.

Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice

PubMed Central

2016-01-01

Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice. PMID:27960282

Lipocalin 2, a Regulator of Retinoid Homeostasis and Retinoid-mediated Thermogenic Activation in Adipose Tissue*

PubMed Central

Guo, Hong; Foncea, Rocio; O'Byrne, Sheila M.; Jiang, Hongfeng; Zhang, Yuanyuan; Deis, Jessica A.; Blaner, William S.; Bernlohr, David A.; Chen, Xiaoli

2016-01-01

We have recently characterized the role of lipocalin 2 (Lcn2) as a new adipose-derived cytokine in the regulation of adaptive thermogenesis via a non-adrenergic pathway. Herein, we explored a potential non-adrenergic mechanism by which Lcn2 regulates thermogenesis and lipid metabolism. We found that Lcn2 is a retinoic acid target gene, and retinoic acid concurrently stimulated UCP1 and Lcn2 expression in adipocytes. Lcn2 KO mice exhibited a blunted effect of all-trans-retinoic acid (ATRA) on body weight and fat mass, lipid metabolism, and retinoic acid signaling pathway activation in adipose tissue under the high fat diet-induced obese condition. We further demonstrated that Lcn2 is required for the full action of ATRA on the induction of UCP1 and PGC-1α expression in brown adipocytes and the restoration of cold intolerance in Lcn2 KO mice. Interestingly, we discovered that Lcn2 KO mice have decreased levels of retinoic acid and retinol in adipose tissue. The protein levels of STRA6 responsible for retinol uptake were significantly decreased in adipose tissue. The retinol transporter RBP4 was increased in adipose tissue but decreased in the circulation, suggesting the impairment of RBP4 secretion in Lcn2 KO adipose tissue. Moreover, Lcn2 deficiency abolished the ATRA effect on RBP4 expression in adipocytes. All the data suggest that the decreased retinoid level and action are associated with impaired retinol transport and storage in adipose tissue in Lcn2 KO mice. We conclude that Lcn2 plays a critical role in regulating metabolic homeostasis of retinoids and retinoid-mediated thermogenesis in adipose tissue. PMID:27008859

Eicosapentaenoic acid reduces adipocyte hypertrophy and inflammation in diet-induced obese mice in an adiposity-independent manner.

PubMed

LeMieux, Monique J; Kalupahana, Nishan S; Scoggin, Shane; Moustaid-Moussa, Naima

2015-03-01

Obesity is associated with an overexpansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation, and thrombosis. Research to develop nutritional interventions to prevent or treat obesity and its associated diseases is greatly needed. Previously, we demonstrated the ability of eicosapentaenoic acid (EPA) to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation in mice. The objective of the current study was to determine the mechanisms mediating the anti-inflammatory and antilipogenic actions of EPA. In a previous study, male C57BL/6J mice were fed a low-fat diet (10% of energy from fat), an HF diet (45% of energy from fat), or an HF diet supplemented with EPA (45% of energy from fat; 36 g/kg EPA; HF+EPA) for 11 wk or an HF diet for 6 wk and then switched to the HF+EPA diet for 5 wk. In this study, we used histology/immunohistochemistry, gene expression, and metabolomic analyses of white adipose tissue from these mice. In addition, cultured mouse 3T3-L1 adipocytes were treated with 100 μM EPA for 48 h and then used for extracellular flux assays with untreated 3T3-L1 adipocytes used as a control. Compared with the HF diet, the HF+EPA diet significantly reduced body weight, adiposity, adipocyte size, and macrophage infiltration into adipose tissue. No significant differences in overall body weight or fat pad weights were observed between HF-fed mice vs. those fed the HF+EPA diet for a short time after first inducing obesity with the HF diet. Interestingly, both histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed the HF diet and then switched to the HF+EPA diet vs. those fed HF diets only. This indicated that EPA was able to prevent as well as reverse HF-diet-induced adipocyte inflammation and hypertrophy and that some of the metabolic effects of EPA were independent of body weight or adiposity. In addition, adipose tissue metabolomic data and cultured adipocyte extracellular flux bioenergetic assays indicated that EPA also regulated mitochondrial function by increasing fatty acid oxidation and oxygen consumption, respectively. With the use of mice and cultured adipocytes, we showed that EPA ameliorates HF-diet effects at least in part by increasing oxygen consumption and fatty acid oxidation and reducing adipocyte size, adipogenesis, and adipose tissue inflammation, independent of obesity. © 2015 American Society for Nutrition.

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

Carbenoxolone Treatment Ameliorated Metabolic Syndrome in WNIN/Ob Obese Rats, but Induced Severe Fat Loss and Glucose Intolerance in Lean Rats

PubMed Central

Prasad Sakamuri, Siva Sankara Vara; Sukapaka, Mahesh; Prathipati, Vijay Kumar; Nemani, Harishankar; Putcha, Uday Kumar; Pothana, Shailaja; Koppala, Swarupa Rani; Ponday, Lakshmi Raj Kumar; Acharya, Vani; Veetill, Giridharan Nappan; Ayyalasomayajula, Vajreswari

2012-01-01

Background 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX) on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. Methodology/Principal Findings Subcutaneous injection of CBX (50 mg/kg body weight) or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment). Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. Conclusions/Significance We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions. PMID:23284633

Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women.

PubMed

Alvehus, Malin; Simonyte, Kotryna; Andersson, Therése; Söderström, Ingegerd; Burén, Jonas; Rask, Eva; Mattsson, Cecilia; Olsson, Tommy

2012-11-01

The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease that are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared with premenopausal women. We also wanted to determine whether these markers are reduced by stable weight loss in obese women. Anthropometric data, blood samples and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass (GBP) surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal vs premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal vs premenopausal women. Two years after GBP surgery, adipose expression of IL-8, tumour necrosis factor-α and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before GBP surgery, but these associations disappeared after surgery. Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.

Dietary sodium, adiposity, and inflammation in healthy adolescents.

PubMed

Zhu, Haidong; Pollock, Norman K; Kotak, Ishita; Gutin, Bernard; Wang, Xiaoling; Bhagatwala, Jigar; Parikh, Samip; Harshfield, Gregory A; Dong, Yanbin

2014-03-01

To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents. A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1. The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps < .05). No relation was found between dietary sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates < 0.05). The mean sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption.

Dietary Sodium, Adiposity, and Inflammation in Healthy Adolescents

PubMed Central

Pollock, Norman K.; Kotak, Ishita; Gutin, Bernard; Wang, Xiaoling; Bhagatwala, Jigar; Parikh, Samip; Harshfield, Gregory A.; Dong, Yanbin

2014-01-01

OBJECTIVES: To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents. METHODS: A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1. RESULTS: The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps < .05). No relation was found between dietary sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates < 0.05). CONCLUSIONS: The mean sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption. PMID:24488738

Effects of acupuncture therapy on abdominal fat and hepatic fat content in obese children: a magnetic resonance imaging and proton magnetic resonance spectroscopy study.

PubMed

Zhang, Hong; Peng, Yun; Liu, ZuXiang; Li, Shilian; Lv, Zhongli; Tian, LiFang; Zhu, Jie; Zhao, XuNa; Chen, Min

2011-05-01

The aim of this study was to use magnetic resonance imaging (MRI) together with proton magnetic resonance spectroscopy ((1)H-MRS) to study the influence of acupuncture therapy on abdominal fat and hepatic fat content in obese children. The design was a longitudinal, clinical intervention study of acupuncture therapy. SUBJECTS were 10 healthy, obese children (age: 11.4 ± 1.65 years, body-mass index [BMI]: 29.03 ± 4.81 kg/m(2)). Measurements included various anthropometric parameters, abdominal fat (assessed by MRI) and hepatic fat content (assessed by (1)H-MRS) at baseline and after 1 month of acupuncture therapy. One (1) month of acupuncture therapy significantly reduced the subjects' BMI by 3.5% (p = 0.005), abdominal visceral adipose tissue (VAT) volume by 16.04% (p < 0.0001), abdominal total adipose tissue volume by 10.45% (p = 0.001), and abdominal visceral to subcutaneous fat ratio by 10.59% (p = 0.007). Decreases in body weight (-2.13%), waist circumference (-1.44%), hip circumference (-0.33%), waist-to-hip ratio (WHR) (-0.99%), abdominal subcutaneous adipose tissue (SAT) volume (-5.63%), and intrahepatic triglyceride (IHTG) content (-9.03%) were also observed, although these were not significant (p > 0.05). There was a significant correlation between the level of abdominal fat (SAT, VAT) and anthropometric parameters (weight, BMI, waist circumferences, hip circumferences). There was no statistically significant correlation between IHTG and anthropometric parameters or abdominal fat content. The first direct experimental evidence is provided demonstrating that acupuncture therapy significantly reduces BMI and abdominal adipose tissue by reducing abdominal VAT content without significant changes in body weight, waist circumference, hip circumference, WHR, abdominal SAT, or IHTG content. Thus, the use of acupuncture therapy to selectively target a reduction in abdominal VAT content should become more important and more popular in the future.

A mouse model for a partially inactive obesity-associated human MC3R variant

PubMed Central

Lee, Bonggi; Koo, Jashin; Yun Jun, Joo; Gavrilova, Oksana; Lee, Yongjun; Seo, Arnold Y.; Taylor-Douglas, Dezmond C.; Adler-Wailes, Diane C.; Chen, Faye; Gardner, Ryan; Koutzoumis, Dimitri; Sherafat Kazemzadeh, Roya; Roberson, Robin B.; Yanovski, Jack A.

2016-01-01

We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3RhWT/hWT) and double-mutant (C17A+G241A) human (MC3RhDM/hDM) MC3R, that MC3RhDM/hDM have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3RhWT/hWT. MC3RhDM/hDM mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3RhDM/hDM mice and MC3RhDM/hDM human subjects. MC3RhDM/hDM bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3RhWT/hWT MSCs. MC3RhDM/hDM impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. PMID:26818770

Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

PubMed

Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

2016-01-01

Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.

Perivascular Adipose Tissue as a Relevant Fat Depot for Cardiovascular Risk in Obesity.

PubMed

Costa, Rafael M; Neves, Karla B; Tostes, Rita C; Lobato, Núbia S

2018-01-01

Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out.

Rosiglitazone-Induced Mitochondrial Biogenesis in White Adipose Tissue Is Independent of Peroxisome Proliferator-Activated Receptor γ Coactivator-1α

PubMed Central

Pardo, Rosario; Enguix, Natàlia; Lasheras, Jaime; Feliu, Juan E.; Kralli, Anastasia; Villena, Josep A.

2011-01-01

Background Thiazolidinediones, a family of insulin-sensitizing drugs commonly used to treat type 2 diabetes, are thought to exert their effects in part by promoting mitochondrial biogenesis in white adipose tissue through the transcriptional coactivator PGC-1α (Peroxisome Proliferator-Activated Receptor γ Coactivator-1α). Methodology/Principal Findings To assess the role of PGC-1α in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1α specifically in adipose tissues (PGC-1α-FAT-KO mice). We found that expression of genes encoding for mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation, was similar in white adipose tissue of wild type and PGC-1α-FAT-KO mice. Furthermore, the absence of PGC-1α did not prevent the positive effect of rosiglitazone on mitochondrial gene expression or biogenesis, but it precluded the induction by rosiglitazone of UCP1 and other brown fat-specific genes in white adipose tissue. Consistent with the in vivo findings, basal and rosiglitazone-induced mitochondrial gene expression in 3T3-L1 adipocytes was unaffected by the knockdown of PGC-1α but it was impaired when PGC-1β expression was knockdown by the use of specific siRNA. Conclusions/Significance These results indicate that in white adipose tissue PGC-1α is dispensable for basal and rosiglitazone-induced mitochondrial biogenesis but required for the rosiglitazone-induced expression of UCP1 and other brown adipocyte-specific markers. Our study suggests that PGC-1α is important for the appearance of brown adipocytes in white adipose tissue. Our findings also provide evidence that PGC-1β and not PGC-1α regulates basal and rosiglitazone-induced mitochondrial gene expression in white adipocytes. PMID:22087241

Soft tissue fillers for adipose tissue regeneration: From hydrogel development toward clinical applications.

PubMed

Van Nieuwenhove, I; Tytgat, L; Ryx, M; Blondeel, P; Stillaert, F; Thienpont, H; Ottevaere, H; Dubruel, P; Van Vlierberghe, S

2017-11-01

There is a clear and urgent clinical need to develop soft tissue fillers that outperform the materials currently used for adipose tissue reconstruction. Recently, extensive research has been performed within this field of adipose tissue engineering as the commercially available products and the currently existing techniques are concomitant with several disadvantages. Commercial products are highly expensive and associated with an imposing need for repeated injections. Lipofilling or free fat transfer has an unpredictable outcome with respect to cell survival and potential resorption of the fat grafts. Therefore, researchers are predominantly investigating two challenging adipose tissue engineering strategies: in situ injectable materials and porous 3D printed scaffolds. The present work provides an overview of current research encompassing synthetic, biopolymer-based and extracellular matrix-derived materials with a clear focus on emerging fabrication technologies and developments realized throughout the last decade. Moreover, clinical relevance of the most promising materials will be discussed, together with potential concerns associated with their application in the clinic. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

PubMed Central

Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

2015-01-01

Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia – before severe fat loss – in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34–42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

Obesogenic diets have deleterious effects on fat deposits irrespective of the nature of dietary carbohydrates in a Yucatan minipig model.

PubMed

Ochoa, Melissa; Val-Laillet, David; Lallès, Jean-Paul; Meurice, Paul; Malbert, Charles-Henri

2016-09-01

The effects of digestible carbohydrates, fructose in particular, on the development of metabolic disturbances remain controversial. We explored the effects of prolonged consumption of high-fat diets differing in their carbohydrate source on fat deposits in the adult Yucatan minipig. Eighteen minipigs underwent computed tomographic imaging and blood sampling before and after 8 weeks of three isocaloric high-fat diets with different carbohydrate sources (20% by weight for starch in the control diet, glucose or fructose, n=6 per diet). Body adiposity, liver volume, and fat content were estimated from computed tomographic images (n=18). Liver volume and lipid content were also measured post mortem (n=12). We hypothesized that the quantity and the spatial distribution of fat deposits in the adipose tissue or in the liver would be altered by the nature of the carbohydrate present in the obesogenic diet. After 8 weeks of dietary exposure, body weight (from 26±4 to 58±3 kg), total body adiposity (from 38±1 to 47±1%; P<.0001), liver volume (from 1156±31 to 1486±66 mL; P<.0001), plasma insulin (from 10±1 to 14±2 mIU/L; P=.001), triacylglycerol (from 318±37 to 466±33 mg/L; P=.005), and free-fatty acids (from 196±60 to 396±59 μmol/L; P=.0001) increased irrespective of the carbohydrate type. Similarly, the carbohydrate type did not induce changes in the spatial repartition of the adipose tissue. Divergent results were obtained for fat deposits in the liver depending on the investigation method. In conclusion, obesogenic diets alter adipose tissue fat deposits and the metabolic profile independently of the nature of dietary carbohydrates. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice.

PubMed

Acedo, Simone Coghetto; Caria, Cintia Rabelo E Paiva; Gotardo, Érica Martins Ferreira; Pereira, José Aires; Pedrazzoli, José; Ribeiro, Marcelo Lima; Gambero, Alessandra

2015-10-28

To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet (HFD). Male swiss mice (6-wk old) were fed a high-fat diet (HFD; 60% kcal from fat) or AIN-93 (control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally (100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis (macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor (TNF)-α in liver (156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced (23.2 ± 6.9 and 12.1 ± 1.6 U/L for non-treated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α (106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6 (340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin (8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1 (600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non-treated and treated lean mice, respectively; P < 0.05) levels increased in lean adipose tissue. TNF-α level in the liver of lean mice also increased (29.6 ± 6.6 and 75.4 ± 12.6 pg/mL for non-treated and treated lean mice, respectively; P < 0.05) while triglycerides presented a tendency to reduction. Pentoxifylline was beneficial in obese mice improving liver and adipose tissue inflammation. Unexpectedly, pentoxifylline increased pro-inflammatory markers in the liver and adipose tissue of lean mice.

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

PubMed Central

Acedo, Simone Coghetto; Caria, Cintia Rabelo e Paiva; Gotardo, Érica Martins Ferreira; Pereira, José Aires; Pedrazzoli, José; Ribeiro, Marcelo Lima; Gambero, Alessandra

2015-01-01

AIM: To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet (HFD). METHODS: Male swiss mice (6-wk old) were fed a high-fat diet (HFD; 60% kcal from fat) or AIN-93 (control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally (100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis (macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. RESULTS: Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor (TNF)-α in liver (156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced (23.2 ± 6.9 and 12.1 ± 1.6 U/L for non-treated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α (106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6 (340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin (8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1 (600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non-treated and treated lean mice, respectively; P < 0.05) levels increased in lean adipose tissue. TNF-α level in the liver of lean mice also increased (29.6 ± 6.6 and 75.4 ± 12.6 pg/mL for non-treated and treated lean mice, respectively; P < 0.05) while triglycerides presented a tendency to reduction. CONCLUSION: Pentoxifylline was beneficial in obese mice improving liver and adipose tissue inflammation. Unexpectedly, pentoxifylline increased pro-inflammatory markers in the liver and adipose tissue of lean mice. PMID:26523207

Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat.

PubMed

Cypess, Aaron M; White, Andrew P; Vernochet, Cecile; Schulz, Tim J; Xue, Ruidan; Sass, Christina A; Huang, Tian Liang; Roberts-Toler, Carla; Weiner, Lauren S; Sze, Cathy; Chacko, Aron T; Deschamps, Laura N; Herder, Lindsay M; Truchan, Nathan; Glasgow, Allison L; Holman, Ashley R; Gavrila, Alina; Hasselgren, Per-Olof; Mori, Marcelo A; Molla, Michael; Tseng, Yu-Hua

2013-05-01

The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1). BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue. In addition to this nonshivering thermogenesis, human BAT may also combat weight gain by becoming more active in the setting of increased whole-body energy intake. This phenomenon of BAT-mediated diet-induced thermogenesis has been observed in rodents and suggests that activation of human BAT could be used as a safe treatment for obesity and metabolic dysregulation. In this study, we isolated anatomically defined neck fat from adult human volunteers and compared its gene expression, differentiation capacity and basal oxygen consumption to different mouse adipose depots. Although the properties of human neck fat vary substantially between individuals, some human samples share many similarities with classical, also called constitutive, rodent BAT.

Laser-induced lipolysis on adipose cells

NASA Astrophysics Data System (ADS)

Solarte, Efrain; Gutierrez, O.; Neira, Rodrigo; Arroyave, J.; Isaza, Carolina; Ramirez, Hugo; Rebolledo, Aldo F.; Criollo, Willian; Ortiz, C.

2004-10-01

Recently, a new liposuction technique, using a low-level laser (LLL) device and Ultrawet solution prior to the procedure, demonstrated the movement of fat from the inside to the outside of the adipocyte (Neira et al., 2002). To determine the mechanisms involved, we have performed Scanning and Transmission Electron Microscopy studies; Light transmittance measurements on adipocyte dilutions; and a study of laser light propagation in adipose tissue. This studies show: 1. Cellular membrane alterations. 2. LLL is capable to reach the deep adipose tissue layer, and 3. The tumescence solution enhances the light propagation by clearing the tissue. MRI studies demonstrated the appearance of fat on laser treated abdominal tissue. Besides, adipocytes were cultivated and irradiated to observe the effects on isolated cells. These last studies show: 1. 635 nm-laser alone is capable of mobilizing cholesterol from the cell membrane; this action is enhanced by the presence of adrenaline and lidocaine. 2. Intracellular fat is released from adipocytes by co joint action of adrenaline, aminophyline and 635 nm-laser. Results are consistent with a laser induced cellular process, which causes fat release from the adipocytes into the intercellular space, besides the modification of the cellular membranes.

A polyphenolic extract from green tea leaves activates fat browning in high-fat-diet-induced obese mice.

PubMed

Neyrinck, Audrey M; Bindels, Laure B; Geurts, Lucie; Van Hul, Matthias; Cani, Patrice D; Delzenne, Nathalie M

2017-11-01

Fat browning has emerged as an attractive target for the treatment of obesity and related metabolic disorders. Its activation leads to increased energy expenditure and reduced adiposity, thus contributing to a better energy homeostasis. Green tea extracts (GTEs) were shown to attenuate obesity and low-grade inflammation and to induce the lipolytic pathway in the white adipose tissue (WAT) of mice fed a high-fat diet. The aim of the present study was to determine whether the antiobesity effect of an extract from green tea leaves was associated with the activation of browning in the WAT and/or the inhibition of whitening in the brown adipose tissue (BAT) in HF-diet induced obese mice. Mice were fed a control diet or an HF diet supplemented with or without 0.5% polyphenolic GTE for 8 weeks. GTE supplementation significantly reduced HF-induced adiposity (WAT and BAT) and HF-induced inflammation in WAT. Histological analysis revealed that GTE reduced the adipocyte size in the WAT and the lipid droplet size in the BAT. Markers of browning were induced in the WAT upon GTE treatment, whereas markers of HF-induced whitening were reduced in the BAT. These results suggest that browning activation in the WAT and whitening reduction in the BAT by the GTE could participate to the improvement of metabolic and inflammatory disorders mediated by GTE upon HF diet. Our study emphasizes the importance of using GTE as a nutritional tool to activate browning and to decrease fat storage in all adipose tissues, which attenuate obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy

PubMed Central

Shimomura, Iichiro; Hammer, Robert E.; Richardson, James A.; Ikemoto, Shinji; Bashmakov, Yuriy; Goldstein, Joseph L.; Brown, Michael S.

1998-01-01

Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPα, PPARγ, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFα were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans. PMID:9784493

Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density.

PubMed

Chi, Jingyi; Wu, Zhuhao; Choi, Chan Hee J; Nguyen, Lily; Tegegne, Saba; Ackerman, Sarah E; Crane, Audrey; Marchildon, François; Tessier-Lavigne, Marc; Cohen, Paul

2018-01-09

While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1 + beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Adipose tissue transcriptome changes during obesity development in female dogs.

PubMed

Grant, Ryan W; Vester Boler, Brittany M; Ridge, Tonya K; Graves, Thomas K; Swanson, Kelly S

2011-03-29

During the development of obesity, adipose tissue undergoes major expansion and remodeling, but the biological processes involved in this transition are not well understood. The objective of this study was to analyze global gene expression profiles of adipose tissue in dogs, fed a high-fat diet, during the transition from a lean to obese phenotype. Nine female beagles (4.09 ± 0.64 yr; 8.48 ± 0.35 kg) were randomized to ad libitum feeding or body weight maintenance. Subcutaneous adipose tissue biopsy, blood, and dual x-ray absorptiometry measurements were collected at 0, 4, 8, 12, and 24 wk of feeding. Serum was analyzed for glucose, insulin, fructosamine, triglycerides, free fatty acids, adiponectin, and leptin. Formalin-fixed adipose tissue was used for determination of adipocyte size. Adipose RNA samples were hybridized to Affymetrix Canine 2.0 microarrays. Statistical analysis, using repeated-measures ANOVA, showed ad libitum feeding increased (P < 0.05) body weight (0 wk, 8.36 ± 0.34 kg; 24 wk, 14.64 ± 0.34 kg), body fat mass (0 wk, 1.36 ± 0.24 kg; 24 wk, 6.52 ± 0.24 kg), adipocyte size (0 wk, 114.66 ± 17.38 μm(2); 24 wk, 320.97 ± 0.18.17 μm(2)), and leptin (0 wk, 0.8 ± 1.0 ng/ml; 24 wk, 12.9 ± 1.0 ng/ml). Microarrays displayed 1,665 differentially expressed genes in adipose tissue as weight increased. Alterations were seen in adipose tissue homeostatic processes including metabolism, oxidative stress, mitochondrial homeostasis, and extracellular matrix. Adipose transcriptome changes highlight the dynamic and adaptive response to ad libitum feeding and obesity development.

Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

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

Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.

1988-09-01

To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific bindingmore » of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.« less

Quantitative CT imaging for adipose tissue analysis in mouse model of obesity

NASA Astrophysics Data System (ADS)

Marchadier, A.; Vidal, C.; Tafani, J.-P.; Ordureau, S.; Lédée, R.; Léger, C.

2011-03-01

In obese humans CT imaging is a validated method for follow up studies of adipose tissue distribution and quantification of visceral and subcutaneous fat. Equivalent methods in murine models of obesity are still lacking. Current small animal micro-CT involves long-term X-ray exposure precluding longitudinal studies. We have overcome this limitation by using a human medical CT which allows very fast 3D imaging (2 sec) and minimal radiation exposure. This work presents novel methods fitted to in vivo investigations of mice model of obesity, allowing (i) automated detection of adipose tissue in abdominal regions of interest, (ii) quantification of visceral and subcutaneous fat. For each mouse, 1000 slices (100μm thickness, 160 μm resolution) were acquired in 2 sec using a Toshiba medical CT (135 kV, 400mAs). A Gaussian mixture model of the Hounsfield curve of 2D slices was computed with the Expectation Maximization algorithm. Identification of each Gaussian part allowed the automatic classification of adipose tissue voxels. The abdominal region of interest (umbilical) was automatically detected as the slice showing the highest ratio of the Gaussian proportion between adipose and lean tissues. Segmentation of visceral and subcutaneous fat compartments was achieved with 2D 1/2 level set methods. Our results show that the application of human clinical CT to mice is a promising approach for the study of obesity, allowing valuable comparison between species using the same imaging materials and software analysis.

Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

PubMed

Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

2012-12-01

Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p < 0.001) as compared to LND group. In SAT we found positive correlation between HOMA-IR and C16:0-Cer (r = 0.79, p < 0.001) and between HOMA-IR and C16:0/18:2 DAG (r = 0.56, p < 0.001). In EAT we found a strong correlation between C16:0-CoA content and HOMA-IR (r = 0.73, p < 0.001). The study showed that in obese and obese diabetic patients, bioactive lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

Transcriptome analysis of adipose tissues from two fat-tailed sheep breeds reveals key genes involved in fat deposition.

PubMed

Li, Baojun; Qiao, Liying; An, Lixia; Wang, Weiwei; Liu, Jianhua; Ren, Youshe; Pan, Yangyang; Jing, Jiongjie; Liu, Wenzhong

2018-05-08

The level of fat deposition in carcass is a crucial factor influencing meat quality. Guangling Large-Tailed (GLT) and Small-Tailed Han (STH) sheep are important local Chinese fat-tailed breeds that show distinct patterns of fat depots. To gain a better understanding of fat deposition, transcriptome profiles were determined by RNA-sequencing of perirenal, subcutaneous, and tail fat tissues from both the sheep breeds. The common highly expressed genes (co-genes) in all the six tissues, and the genes that were differentially expressed (DE genes) between these two breeds in the corresponding tissues were analyzed. Approximately 47 million clean reads were obtained for each sample, and a total of 17,267 genes were annotated. Of the 47 highly expressed co-genes, FABP4, ADIPOQ, FABP5, and CD36 were the four most highly transcribed genes among all the known genes related to adipose deposition. FHC, FHC-pseudogene, and ZC3H10 were also highly expressed genes and could, thus, have roles in fat deposition. A total of 2091, 4233, and 4131 DE genes were identified in the perirenal, subcutaneous, and tail fat tissues between the GLT and STH breeds, respectively. Gene Ontology (GO) analysis showed that some DE genes were associated with adipose metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PPAR signaling pathway and ECM-receptor interaction were specifically enriched. Four genes, namely LOC101102230, PLTP, C1QTNF7, and OLR1 were up-regulated and two genes, SCD and UCP-1, were down-regulated in all the tested tissues of STH. Among the genes involved in ECM-receptor interaction, the genes encoding collagens, laminins, and integrins were quite different depending on the depots or the breeds. In STH, genes such as LAMB3, RELN, TNXB, and ITGA8, were identified to be up regulated and LAMB4 was observed to be down regulated. This study unravels the complex transcriptome profiles in sheep fat tissues, highlighting the candidate genes involved in fat deposition. Further studies are needed to investigate the roles of the candidate genes in fat deposition and in determining the meat quality of sheep.

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.

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

Extended Multiplexing of Tandem Mass Tags (TMT) Labeling Reveals Age and High Fat Diet Specific Proteome Changes in Mouse Epididymal Adipose Tissue*

PubMed Central

Plubell, Deanna L.; Wilmarth, Phillip A.; Zhao, Yuqi; Fenton, Alexandra M.; Minnier, Jessica; Reddy, Ashok P.; Klimek, John; Yang, Xia; David, Larry L.

2017-01-01

The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low versus high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism (e.g. AACS, ACOX1, ACLY) and red-ox pathways (e.g. CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response (e.g. IGTB2, IFIT3, LGALS1) and rennin angiotensin system (e.g. ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle (e.g. OTC, ARG1, CPS1), and amino acid biosynthesis (e.g. GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle (e.g. ARG1, CPS1), immune response/complement activation (e.g. C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling (e.g. EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis (e.g. YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953. PMID:28325852

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice.

PubMed

Lecomte, Manon; Couëdelo, Leslie; Meugnier, Emmanuelle; Plaisancié, Pascale; Létisse, Marion; Benoit, Bérengère; Gabert, Laure; Penhoat, Armelle; Durand, Annie; Pineau, Gaëlle; Joffre, Florent; Géloën, Alain; Vaysse, Carole; Laugerette, Fabienne; Michalski, Marie-Caroline

2016-03-01

Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p < 0.05), with larger adipocytes (p < 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p < 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p < 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p < 0.05), and more goblet cells in the colon (p < 0.05). Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial.

PubMed

Perfilyev, Alexander; Dahlman, Ingrid; Gillberg, Linn; Rosqvist, Fredrik; Iggman, David; Volkov, Petr; Nilsson, Emma; Risérus, Ulf; Ling, Charlotte

2017-04-01

Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses. Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial. Design: We studied the effects of 7 wk of excessive SFA ( n = 17) or PUFA ( n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue. Both diets resulted in similar body weight increases. We also combined the data from the 2 groups to examine the overall effect of overfeeding on the DNA methylation in adipose tissue. Results: The DNA methylation of 4875 Cytosine-phosphate-guanine (CpG) sites was affected differently between the 2 diets. Furthermore, both the SFA and PUFA diets increased the mean degree of DNA methylation in adipose tissue, particularly in promoter regions. However, although the mean methylation was changed in 1797 genes [e.g., alpha-ketoglutarate dependent dioxygenase ( FTO ), interleukin 6 ( IL6 ), insulin receptor ( INSR ), neuronal growth regulator 1 ( NEGR1 ), and proopiomelanocortin ( POMC )] by PUFAs, only 125 genes [e.g., adiponectin, C1Q and collagen domain containing ( ADIPOQ )] were changed by SFA overfeeding. In addition, the SFA diet significantly altered the expression of 28 transcripts [e.g., acyl-CoA oxidase 1 ( ACOX1 ) and FAT atypical cadherin 1 ( FAT1 )], whereas the PUFA diet did not significantly affect gene expression. When the data from the 2 diet groups were combined, the mean methylation of 1444 genes, including fatty acid binding protein 1 ( FABP1 ), fatty acid binding protein 2 ( FABP2 ), melanocortin 2 receptor ( MC2R ), MC3R , PPARG coactivator 1 α ( PPARGC1A ), and tumor necrosis factor ( TNF ), was changed in adipose tissue by overfeeding. Moreover, the baseline DNA methylation of 12 CpG sites that was annotated to 9 genes [e.g., mitogen-activated protein kinase 7 ( MAPK7 ), melanin concentrating hormone receptor 1 ( MCHR1 ), and splicing factor SWAP homolog ( SFRS8 )] was associated with the degree of weight increase in response to extra energy intake. Conclusions: SFA overfeeding and PUFA overfeeding induce distinct epigenetic changes in human adipose tissue. In addition, we present data that suggest that baseline DNA methylation can predict weight increase in response to overfeeding in humans. This trial was registered at clinicaltrials.gov as NCT01427140. © 2017 American Society for Nutrition.

Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages.

PubMed

Chatterjee, Priyajit; Seal, Soma; Mukherjee, Sandip; Kundu, Rakesh; Mukherjee, Sutapa; Ray, Sukanta; Mukhopadhyay, Satinath; Majumdar, Subeer S; Bhattacharya, Samir

2013-09-27

Macrophage infiltration into adipose tissue during obesity and their phenotypic conversion from anti-inflammatory M2 to proinflammatory M1 subtype significantly contributes to develop a link between inflammation and insulin resistance; signaling molecule(s) for these events, however, remains poorly understood. We demonstrate here that excess lipid in the adipose tissue environment may trigger one such signal. Adipose tissue from obese diabetic db/db mice, high fat diet-fed mice, and obese diabetic patients showed significantly elevated fetuin-A (FetA) levels in respect to their controls; partially hepatectomized high fat diet mice did not show noticeable alteration, indicating adipose tissue to be the source of this alteration. In adipocytes, fatty acid induces FetA gene and protein expressions, resulting in its copious release. We found that FetA could act as a chemoattractant for macrophages. To simulate lipid-induced inflammatory conditions when proinflammatory adipose tissue and macrophages create a niche of an altered microenvironment, we set up a transculture system of macrophages and adipocytes; the addition of fatty acid to adipocytes released FetA into the medium, which polarized M2 macrophages to M1. This was further confirmed by direct FetA addition to macrophages. Taken together, lipid-induced FetA from adipocytes is an efficient chemokine for macrophage migration and polarization. These findings open a new dimension for understanding obesity-induced inflammation.

Allele Compensation in Tip60+/− Mice Rescues White Adipose Tissue Function In Vivo

PubMed Central

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/− mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/− mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/− displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/− mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice. PMID:24870614

Serum Adipokines and Adipose Tissue Distribution in Rheumatoid Arthritis and Ankylosing Spondylitis. A Comparative Study

PubMed Central

Toussirot, Éric; Grandclément, Émilie; Gaugler, Béatrice; Michel, Fabrice; Wendling, Daniel; Saas, Philippe; Dumoulin, Gilles

2013-01-01

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These results confirm that body composition was altered in RA and AS, affecting distinct soft tissue compartments. The effect of the increased visceral adipose tissue on cardiovascular risk is presumably attenuated by the favorable cardiometabolic profile in women with RA, as suggested by the normal HOMA-IR and atherogenic index. PMID:24379815

Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study.

PubMed

Toussirot, Eric; Grandclément, Emilie; Gaugler, Béatrice; Michel, Fabrice; Wendling, Daniel; Saas, Philippe; Dumoulin, Gilles

2013-01-01

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These results confirm that body composition was altered in RA and AS, affecting distinct soft tissue compartments. The effect of the increased visceral adipose tissue on cardiovascular risk is presumably attenuated by the favorable cardiometabolic profile in women with RA, as suggested by the normal HOMA-IR and atherogenic index.

Comparison of Gross Body Fat-Water Magnetic Resonance Imaging at 3 Tesla to Dual Energy X-Ray Absorptiometry in Obese Women

PubMed Central

Silver, HJ; Niswender, KD; Kullberg, J; Berglund, J; Johansson, L; Bruvold, M; Avison, MJ; Welch, EB.

2012-01-01

Improved understanding of how depot-specific adipose tissue mass predisposes to obesity-related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three-dimensional contiguous “fat-water” MR imaging (FWMRI) covering the majority of a whole-body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type and distribution of adipose and lean soft tissue would show great promise in body composition methodology. Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to DEXA. Anthropometric, FWMRI and DEXA measurements were obtained in twelve women with BMI 30–39.9 kg/m2. Test-retest results found coefficients of variation for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DEXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST and TTLST, respectively. While Bland Altman plots demonstrated agreement between FWMRI and DEXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DEXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully-automated segmentation is fast (<30 minutes total scan and post-processing time), noninvasive, repeatable and cost effective. PMID:23712980

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.

Preparation of a nano emodin transfersome and study on its anti-obesity mechanism in adipose tissue of diet-induced obese rats

PubMed Central

2014-01-01

Objective To describe the preparation of nano emodin transfersome (NET) and investigate its effect on mRNA expression of adipose triglyceride lipase (ATGL) and G0/G1 switch gene 2 (G0S2) in adipose tissue of diet-induced obese rats. Methods NET was prepared by film-ultrasonic dispersion method. The effects of emodin components at different ratios on encapsulation efficiency were investigated.The NET envelopment rate was determined by ultraviolet spectrophotometry. The particle size and Zeta potential of NET were evaluated by Zetasizer analyzer. Sixty male SD rats were assigned to groups randomly. After 8-week treatment, body weight, wet weight of visceral fat and the percentage of body fat (PBF) were measured. Fasting blood glucose and serum lipid levels were determined. The adipose tissue section was HE stained, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expression of ATGL and G0S2 from the peri-renal fat tissue was assayed by RT-PCR. Results The appropriate formulation was deoxycholic acid sodium salt vs. phospholipids 1:8, cholesterol vs. phospholipids 1:3, vitamin Evs. phospholipids 1:20, and emodin vs. phospholipid 1:6. Zeta potential was −15.11 mV, and the particle size was 292.2 nm. The mean encapsulation efficiency was (69.35 ± 0.25)%. Compared with the obese model group, body weight, wet weight of visceral fat, PBF and mRNA expression of G0S2 from peri-renal fat tissue were decreased significantly after NET treatment (all P < 0.05), while high-density lipoprotein cholesterol (HDL-C), the diameter of adipocytes and mRNA expression of ATGL from peri-renal fat tissue were increased significantly (all P < 0.05). Conclusion The preparation method is simple and reasonable. NET with negative electricity was small and uniform in particle size, with high encapsulation efficiency and stability. NET could reduce body weight and adipocyte size, and this effect was associated with the up-regulation of ATGL, down-regulation of G0S2 expression in the adipose tissue, and improved insulin sensitivity. PMID:24641917

Laser light propagation in adipose tissue and laser effects on adipose cell membranes

NASA Astrophysics Data System (ADS)

Solarte, Efraín; Rebolledo, Aldo; Gutierrez, Oscar; Criollo, William; Neira, Rodrigo; Arroyave, José; Ramírez, Hugo

2006-01-01

Recently Neira et al. have presented a new liposuction technique that demonstrated the movement of fat from inside to outside of the cell, using a low-level laser device during a liposuction procedure with Ultrawet solution. The clinical observations, allowed this new surgical development, started a set of physical, histological and pharmacological studies aimed to determine the mechanisms involved in the observed fat mobilization concomitant to external laser application in liposuction procedures. Scanning and Transmission Electron Microscopy, studies show that the cellular arrangement of normal adipose tissue changes when laser light from a diode laser: 10 mW, 635 nm is applied. Laser exposures longer than 6 minutes cause the total destruction of the adipocyte panicles. Detailed observation of the adipose cells show that by short irradiation times (less than four minutes) the cell membrane exhibits dark zones, that collapse by longer laser exposures. Optical measurements show that effective penetration length depends on the laser intensity. Moreover, the light scattering is enhanced by diffraction and subsequent interference effects, and the tumescent solution produces a clearing of the tissue optical medium. Finally, isolate adipose cell observation show that fat release from adipocytes is a concomitant effect between the tumescent solution (adrenaline) and laser light, revealing a synergism which conduces to the aperture, and maybe the disruption, of the cell membrane. All these studies were consistent with a laser induced cellular process, which causes fat release from inside the adipocytes into the intercellular space, besides a strong modification of the cellular membranes.

Inflammation in Response to n3 Fatty Acids in a Porcine Obesity Model

PubMed Central

Faris, Richard J; Boddicker, Rebecca L; Walker-Daniels, Jennifer; Li, Jenny; Jones, Douglas E; Spurlock, Michael E

2012-01-01

Fatty acids have distinct cellular effects related to inflammation and insulin sensitivity. Dietary saturated fat activates toll-like receptor 4, which in turn can lead to chronic inflammation, insulin resistance, and adipose tissue macrophage infiltration. Conversely, n3 fatty acids are generally antiinflammatory and promote insulin sensitivity, in part via peroxisome proliferator-activated receptor γ. Ossabaw swine are a useful biomedical model of obesity. We fed Ossabaw pigs either a low-fat control diet or a diet containing high-fat palm oil with or without additional n3 fatty acids for 30 wk to investigate the effect of saturated fats and n3 fatty acids on obesity-linked inflammatory markers. The diet did not influence the inflammatory markers C-reactive protein, TNFα, IL6, or IL12. In addition, n3 fatty acids attenuated the increase in inflammatory adipose tissue CD16–CD14+ macrophages induced by high palm oil. High-fat diets with and without n3 fatty acids both induced hyperglycemia without hyperinsulinemia. The high-fat only group but not the high-fat group with n3 fatty acids showed reduced insulin sensitivity in response to insulin challenge. This effect was not mediated by decreased phosphorylation of protein kinase B. Therefore, in obese Ossabaw swine, n3 fatty acids partially attenuate insulin resistance but only marginally change inflammatory status and macrophage phenotype in adipose tissue. PMID:23561883

The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.

PubMed

Anglim, Breffini; Farah, Nadine; O'Connor, Clare; Daly, Niamh; Kennelly, Mairead M; Turner, Michael J

2017-07-01

Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.

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

Determination of d-limonene in adipose tissue by gas chromatography-mass spectrometry

PubMed Central

Miller, Jessica A.; Hakim, Iman A.; Thomson, Cynthia; Thompson, Patricia; Chow, H-H. Sherry

2008-01-01

We developed a novel method for analyzing d-limonene levels in adipose tissue. Fat samples were subjected to saponification followed by solvent extraction. d-Limonene in the sample extract was analyzed using gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring. Linear calibration curves were established over the mass range of 79.0-2,529 ng d-limonene per 0.1 grams of adipose tissue. Satisfactory within day precision (RSD 6.7 to 9.6%) and accuracy (% difference of −2.7 to 3.8%) and between day precision (RSD 6.0 to 10.7%) and accuracy (% difference of 1.8 to 2.6%) were achieved. The assay was successfully applied to human fat biopsy samples from a d-limonene feeding trial. PMID:18571481

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

O-GlcNAc transferase enables AgRP neurons to suppress browning of white fat

PubMed Central

Ruan, Hai-Bin; Dietrich, Marcelo O.; Liu, Zhong-Wu; Zimmer, Marcelo R.; Li, Min-Dian; Singh, Jay Prakash; Zhang, Kaisi; Yin, Ruonan; Wu, Jing; Horvath, Tamas L.; Yang, Xiaoyong

2014-01-01

SUMMARY Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting. PMID:25303527

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.

Effect of Gender on the Total Abdominal Fat, Intra-Abdominal Adipose Tissue and Abdominal Sub-Cutaneous Adipose Tissue among Indian Hypertensive Patients.

PubMed

Sahoo, Jaya Prakash; Kumari, Savita; Jain, Sanjay

2016-04-01

Abdominal obesity is a better marker of adverse metabolic profile than generalized obesity in hypertensive subjects. Further, gender has effect on adiposity and its distribution. Effect of gender on obesity and the distribution of fat in different sub-compartments of abdomen among Indian hypertensive subjects. This observational study included 278 adult subjects (Males-149 & Females-129) with essential hypertension from a tertiary care centre in north India over one year. A detailed history taking and physical examination including anthropometry were performed in all patients. Total Abdominal Fat (TAF) and abdominal adipose tissue sub-compartments like Intra-Abdominal Adipose Tissue (IAAT) and Sub-Cutaneous Adipose Tissue (SCAT) were measured using the predictive equations developed for Asian Indians. Female hypertensive subjects had higher Body Mass Index (BMI) with more overweight (BMI ≥ 23kg/m(2)), and obesity (BMI≥ 25 kg/m(2)). Additionally, they had higher prevalence of central obesity based on both Waist Circumference (WC) criteria (WC≥ 90 cm in males and WC≥ 80 cm in females) and TAF criteria {≥245.6 cm(2) (males) and ≥203.46 cm(2) (females)} than male patients. But there was no difference in the prevalence of central obesity based on Waist Hip Ratio (WHR) criteria (WHR ≥0.90 in males and WHR ≥ 0.85 in females) between two genders. High TAF & IAAT were present in more females although there was no difference in the distribution of high SCAT between two genders. Female hypertensive subjects were more obese with higher abnormal TAF & IAAT compared to male patients. However, there was no difference in the distribution of high SCAT among them.

Lean phenotype and resistance to diet-induced obesity in vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue.

PubMed

Narvaez, Carmen J; Matthews, Donald; Broun, Emily; Chan, Michelle; Welsh, JoEllen

2009-02-01

Increased adiposity is a feature of aging in both mice and humans, but the molecular mechanisms underlying age-related changes in adipose tissue stores remain unclear. In previous studies, we noted that 18-month-old normocalcemic vitamin D receptor (VDR) knockout (VDRKO) mice exhibited atrophy of the mammary adipose compartment relative to wild-type (WT) littermates, suggesting a role for VDR in adiposity. Here we monitored body fat depots, food intake, metabolic factors, and gene expression in WT and VDRKO mice on the C57BL6 and CD1 genetic backgrounds. Regardless of genetic background, both sc and visceral white adipose tissue depots were smaller in VDRKO mice than WT mice. The lean phenotype of VDRKO mice was associated with reduced serum leptin and compensatory increased food intake. Similar effects on adipose tissue, leptin and food intake were observed in mice lacking Cyp27b1, the 1alpha-hydroxylase enzyme that generates 1,25-dihydroxyvitamin D(3), the VDR ligand. Although VDR ablation did not reduce expression of peroxisome proliferator-activated receptor-gamma or fatty acid synthase, PCR array screening identified several differentially expressed genes in white adipose tissue from WT and VDRKO mice. Uncoupling protein-1, which mediates dissociation of cellular respiration from energy production, was greater than 25-fold elevated in VDRKO white adipose tissue. Consistent with elevation in uncoupling protein-1, VDRKO mice were resistant to high-fat diet-induced weight gain. Collectively, these studies identify a novel role for 1,25-dihydroxyvitamin D(3) and the VDR in the control of adipocyte metabolism and lipid storage in vivo.

Multiaxial mechanical properties and constitutive modeling of human adipose tissue: a basis for preoperative simulations in plastic and reconstructive surgery.

PubMed

Sommer, Gerhard; Eder, Maximilian; Kovacs, Laszlo; Pathak, Heramb; Bonitz, Lars; Mueller, Christoph; Regitnig, Peter; Holzapfel, Gerhard A

2013-11-01

A preoperative simulation of soft tissue deformations during plastic and reconstructive surgery is desirable to support the surgeon's planning and to improve surgical outcomes. The current development of constitutive adipose tissue models, for the implementation in multilayer computational frameworks for the simulation of human soft tissue deformations, has proved difficult because knowledge of the required mechanical parameters of fat tissue is limited. Therefore, for the first time, human abdominal adipose tissues were mechanically investigated by biaxial tensile and triaxial shear tests. The results of this study suggest that human abdominal adipose tissues under quasi-static and dynamic multiaxial loadings can be characterized as a nonlinear, anisotropic and viscoelastic soft biological material. The nonlinear and anisotropic features are consequences of the material's collagenous microstructure. The aligned collagenous septa observed in histological investigations causes the anisotropy of the tissue. A hyperelastic model used in this study was appropriate to represent the quasi-static multiaxial mechanical behavior of fat tissue. The constitutive parameters are intended to serve as a basis for soft tissue simulations using the finite element method, which is an apparent method for obtaining promising results in the field of plastic and reconstructive surgery. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

PubMed

Brøns, Charlotte; Grunnet, Louise Groth

2017-02-01

Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver. © 2017 European Society of Endocrinology.

Correlation of MRI-derived adipose tissue measurements and anthropometric markers with prevalent hypertension in the community.

PubMed

Lorbeer, Roberto; Rospleszcz, Susanne; Schlett, Christopher L; Heber, Sophia D; Machann, Jürgen; Thorand, Barbara; Meisinger, Christa; Heier, Margit; Peters, Annette; Bamberg, Fabian; Lieb, Wolfgang

2018-07-01

To compare the correlations of MRI-derived adipose tissue measurements and anthropometric markers, respectively, with prevalent hypertension in a community-based sample, free of clinical cardiovascular disease. MRI-derived adipose tissue measurements were obtained in 345 participants (143 women; age 39-73 years) of the KORA FF4 survey from Southern Germany using a 3-Tesla machine and included total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SCAT), hepatic fat fraction (HFF), pancreatic fat fraction (PFF) as well as pericardial adipose tissue (PAT). In addition, the anthropometric markers body mass index, waist circumference, hip circumference, waist-hip ratio (WHR) and waist-height ratio (WHtR) as well as blood pressure measurements were obtained. The prevalence of hypertension was 33.6% (women: 28%, men: 38%). VAT and PAT had the highest area under the curve (AUC) values for identifying individuals with prevalent hypertension (AUC: 0.75; 0.73, respectively), whereas WHtR and waist circumference were best performing anthropometric markers (AUC: 0.72; 0.70, respectively). A 1SD increment of TAT was associated with the highest odd for hypertension in the age-adjusted and sex-adjusted model (OR = 2.20, 95% CI 1.67-2.91, P < 0.001) and in the fully adjusted model (OR = 1.97, 95% CI 1.45-2.66, P < 0.001). TAT was the only MRI-derived adipose tissue measurement that was associated with hypertension independently of the best performing anthropometric marker waist circumference in the fully adjusted model (OR = 1.93, 95% CI 1.00-3.72, P = 0.049). MRI-derived adipose tissue measurements perform similarly in identifying prevalent hypertension compared with anthropometric markers. Especially, TAT, VAT and PAT as well as WHtR and waist circumference were highly correlated with prevalent hypertension.

Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population.

PubMed

Lai, Yau-Huei; Yun, Chun-Ho; Su, Cheng-Huang; Yang, Fei-Shih; Yeh, Hung-I; Hou, Charles Jia-Yin; Wu, Tung-Hsin; Cury, Ricardo C; Bezerra, Hiram G; Hung, Chung-Lieh

2016-03-01

Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (β-coef: -0.20 & -0.12, both P < 0.05) after adjusting for clinical variables. Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population. © 2016 The authors.

Mammary Adipose Tissue-derived Lysophospholipids Promote Estrogen Receptor-negative Mammary Epithelial Cell Proliferation

PubMed Central

Volden, Paul A.; Skor, Maxwell N.; Johnson, Marianna B.; Singh, Puneet; Patel, Feenalie N.; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

2016-01-01

Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiological and pathological processes including cancer. LPA is converted to lysophosphatidylcholine (LPC) by the secreted phospholipase, autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA-axis) signaling to breast cancer is poorly understood. Using mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA-axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA-axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA-axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. PMID:26862086

Chronically increased glucose uptake by adipose tissue leads to lactate production and improved insulin sensitivity rather than obesity in the mouse.

PubMed

Muñoz, S; Franckhauser, S; Elias, I; Ferré, T; Hidalgo, A; Monteys, A M; Molas, M; Cerdán, S; Pujol, A; Ruberte, J; Bosch, F

2010-11-01

In adipocytes, triacylglycerol synthesis depends on the formation of glycerol 3-phosphate, which originates either from glucose, through glycolysis, or from lactate, through glyceroneogenesis. However, glucose is traditionally viewed as the main precursor of the glycerol backbone and thus, enhanced glucose uptake would be expected to result in increased triacylglycerol synthesis and contribute to obesity. To further explore this issue, we generated a mouse model with chronically increased glucose uptake in adipose tissue by expressing Gck, which encodes the glucokinase enzyme. Here we show that the production of high levels of glucokinase led to increased adipose tissue glucose uptake and lactate production, improved glucose tolerance and higher whole-body and skeletal muscle insulin sensitivity. There was no parallel increase in glycerol 3-phosphate synthesis in vivo, fat accumulation or obesity. Moreover, at high glucose concentrations, in cultured fat cells overproducing glucokinase, glycerol 3-phosphate synthesis from pyruvate decreased, while glyceroneogenesis increased in fat cells overproducing hexokinase II. These findings indicate that the absence of glucokinase inhibition by glucose 6-phosphate probably led to increased glycolysis and blocked glyceroneogenesis in the mouse model. Furthermore, this study suggests that under physiological conditions, when blood glucose increases, glyceroneogenesis may prevail over glycolysis for triacylglycerol formation because of the inhibition of hexokinase II by glucose 6-phosphate. Together these results point to the indirect pathway (glucose to lactate to glycerol 3-phosphate) being key for fat deposition in adipose tissue.

Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI.

PubMed

Hu, Houchun H; Yin, Larry; Aggabao, Patricia C; Perkins, Thomas G; Chia, Jonathan M; Gilsanz, Vicente

2013-10-01

To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity. Copyright © 2013 Wiley Periodicals, Inc.

Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.

PubMed

McMillen, I C; Muhlhausler, B S; Duffield, J A; Yuen, B S J

2004-08-01

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

Adiposity and hand osteoarthritis: the Netherlands Epidemiology of Obesity study

PubMed Central

2014-01-01

Introduction Obesity, usually characterized by the body mass index (BMI), is a risk factor for hand osteoarthritis (OA). We investigated whether adipose tissue and abdominal fat distribution are associated with hand OA. Methods The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45 to 65 years, including 5315 participants (53% women, median BMI 29.9 kg/m2). Fat percentage and fat mass (FM) (kg) were estimated using bioelectrical impedance analysis. The waist-to-hip ratio (WHR) was calculated. In 1721 participants, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (cm2) were assessed using abdominal MR imaging. Hand OA was defined according to the ACR criteria. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of fat percentage, FM, WHR, VAT and SAT with hand OA using logistic regression analyses per standard deviation, stratified by sex and adjusted for age. Results Hand OA was present in 8% of men and 20% of women. Fat percentage was associated with hand OA in men (OR 1.34 (95% CI 1.11 to 1.61)) and women (OR 1.26 (1.05 to 1.51)), as was FM. WHR was associated with hand OA in men (OR 1.45 (1.13 to 1.85)), and to a lesser extent in women (OR 1.17 (1.00 to 1.36)). Subgroup analysis revealed that VAT was associated with hand OA in men (OR1.33 (1.01 to 1.75)). This association increased after additional adjustment for FM (OR 1.51 (1.13 to 2.03)). Conclusions Fat percentage, FM and WHR were associated with hand OA. VAT was associated with hand OA in men, suggesting involvement of visceral fat in hand OA. PMID:24447395

A Common Variant of NGEF Is Associated with Abdominal Visceral Fat in Korean Men.

PubMed

Kim, Hyun-Jin; Park, Jin-Ho; Lee, Seungbok; Son, Ho-Young; Hwang, Jinha; Chae, Jeesoo; Yun, Jae Moon; Kwon, Hyuktae; Kim, Jong-Il; Cho, Belong

2015-01-01

Central adiposity, rather than body mass index (BMI), is a key pathophysiological feature of the development of obesity-related diseases. Although genetic studies by anthropometric measures such as waist circumference have been widely conducted, genetic studies for abdominal fat deposition measured by computed tomography (CT) have been rarely performed. A total of 1,243 participants who were recruited from two health check-up centers were included in this study. We selected four and three single-nucleotide polymorphisms (SNPs) in NGEF and RGS6, respectively, and analyzed the associations between the seven SNPs and central adiposity measured by CT using an additive, dominant, or recessive model. The participants were generally healthy middle-aged men (50.7 ± 5.3 years). In the additive model, the rs11678490 A allele of NGEF was significantly associated with total adipose tissue, visceral adipose tissue (VAT), and subcutaneous adipose tissue (all P < 0.05). The AA genotype of this SNP in the recessive model showed a more significant association with all adiposity traits, and its association with VAT remained significant even after adjustment for BMI (P = 0.005). In the overall or visceral obesity group analysis, the AA genotype of rs11678490 showed no association with overall obesity (P = 0.148), whereas it was significantly associated with visceral obesity both before (P = 0.010) and after (P = 0.029) adjustment for BMI. In particular, an AA genotype effect was conspicuous between lower and upper groups with 5% extreme VAT phenotypes (OR = 9.59, 95% CI = 1.50-61.31). However, we found no significant association between SNPs of RGS6 and central adiposity. We identified a visceral-fat-associated SNP, rs11678490 of NGEF, in Korean men. This study suggests that the genetic background of central adiposity and BMI is different, and that additional efforts should be made to find the unique genetic architecture of intra-abdominal fat accumulation.

Automated unsupervised multi-parametric classification of adipose tissue depots in skeletal muscle

PubMed Central

Valentinitsch, Alexander; Karampinos, Dimitrios C.; Alizai, Hamza; Subburaj, Karupppasamy; Kumar, Deepak; Link, Thomas M.; Majumdar, Sharmila

2012-01-01

Purpose To introduce and validate an automated unsupervised multi-parametric method for segmentation of the subcutaneous fat and muscle regions in order to determine subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) areas based on data from a quantitative chemical shift-based water-fat separation approach. Materials and Methods Unsupervised standard k-means clustering was employed to define sets of similar features (k = 2) within the whole multi-modal image after the water-fat separation. The automated image processing chain was composed of three primary stages including tissue, muscle and bone region segmentation. The algorithm was applied on calf and thigh datasets to compute SAT and IMAT areas and was compared to a manual segmentation. Results The IMAT area using the automatic segmentation had excellent agreement with the IMAT area using the manual segmentation for all the cases in the thigh (R2: 0.96) and for cases with up to moderate IMAT area in the calf (R2: 0.92). The group with the highest grade of muscle fat infiltration in the calf had the highest error in the inner SAT contour calculation. Conclusion The proposed multi-parametric segmentation approach combined with quantitative water-fat imaging provides an accurate and reliable method for an automated calculation of the SAT and IMAT areas reducing considerably the total post-processing time. PMID:23097409

Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk

PubMed Central

Vasan, S K; Osmond, C; Canoy, D; Christodoulides, C; Neville, M J; Di Gravio, C; Fall, C H D; Karpe, F

2018-01-01

Background/Objectives: Fat distribution is a strong and independent predictor of type 2 diabetes (T2D) and cardiovascular disease (CVD) and is usually determined using conventional anthropometry in epidemiological studies. Dual-energy X-ray absorptiometry (DXA) can measure total and regional adiposity more accurately. Nonetheless, whether DXA provides more precise estimates of cardiovascular risk in relation to total and regional adiposity is not known. We determined the strength of the associations between DXA- and conventional anthropometry determined fat distribution and T2D and CVD risk markers. Subjects/Methods: Waist (WC) and hip circumference (HC) and DXA was used to measure total and regional adiposity in 4950 (2119 men) participants aged 29–55 years from the Oxford Biobank without pre-existing T2D or CVD. Cross-sectional associations were compared between WC and HC vs. DXA-determined regional adiposity (all z-score normalised) with impaired fasting glucose, hypertriglyceridemia, hypertension and insulin resistance (IR). Results: Following adjustment for total adiposity, upper body adiposity measurements showed consistently increased risk of T2D and CVD risk markers except for abdominal subcutaneous fat in both sexes, and arm fat in men, which showed protective associations. Among upper adiposity depots, visceral fat mass showed stronger odds ratios (OR) ranging from 1.69 to 3.64 compared with WC 1.07–1.83. Among lower adiposity depots, HC showed modest protection for IR in both sexes (men: OR 0.80 (95% confidence interval 0.67, 0.96); women: 0.69 (0.56, 0.86)), whereas gynoid fat and in particular leg fat showed consistent and strong protective effects for all outcomes in both men and women. The differential effect of body fat distribution on CVD and T2D were more pronounced at higher levels of total adiposity. Conclusions: Compared with DXA, conventional anthropometry underestimates the associations of regional adiposity with T2D and CVD risk markers. After correcting for overall adiposity, greater subcutaneous fat mass in particular in the lower body is protective relative to greater android or visceral adipose tissue mass. PMID:29151596

Surgical reduction of adipose tissue in the male Sprague-Dawley rat.

PubMed

Kral, J G

1976-10-01

The lipostatic theory of regulation of adipose tissue mass was tested by a method for surgical reduction (adipectomy) of 24% of the total body fat of nonobese adult Sprague-Dawley rats, as judged from carcass analyses. The reduction persisted during an observation period of 12 wk without any evidence of altered food intake, weight gain, or compensatory hypertrophy or hyperplasia of adipose tissue compared with sham-operated controls. No changes were found in serum free fatty acids, glycerol, triglycerides, cholesterol, or insulin between adipectomized and control animals, implying an intact quantitative function of the remaining adipose tissue. It is concluded that the size of the adipocytes rather than the number is important for a presumed lipostatic regulation of adipose tissue mass in the adult male Sprague-Dawley rat.

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

PubMed Central

Hochberg, Irit; Harvey, Innocence; Tran, Quynh T; Stephenson, Erin J; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave

2015-01-01

Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with nonfunctioning pituitary adenomas (n=11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids. PMID:26150553

Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells

PubMed Central

Okumura, Takashi; Ohuchida, Kenoki; Sada, Masafumi; Abe, Toshiya; Endo, Sho; Koikawa, Kazuhiro; Iwamoto, Chika; Miura, Daisuke; Mizuuchi, Yusuke; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Manabe, Tatsuya; Ohtsuka, Takao; Nagai, Eishi; Mizumoto, Kazuhiro; Oda, Yoshinao; Hashizume, Makoto; Nakamura, Masafumi

2017-01-01

Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion. Mice fed a high fat diet had significantly larger primary pancreatic tumors and a significantly higher rate of distant organ metastasis than mice fed a standard diet. In the organotypic fat invasion model, pancreatic cancer cell clusters were smaller and more elongated in shape and showed increased fibrosis. Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell invasiveness and gemcitabine resistance, as well as inducing morphologic changes in cancer cells and increasing the numbers of lipid droplets in their cytoplasm. The concentrations of oleic, palmitoleic, and linoleic acids were higher in adipose tissue-derived conditioned medium than in normal medium, with these fatty acids significantly enhancing the migration of cancer cells. Mature adipocytes were smaller and the concentration of fatty acids in the medium higher when these cells were co-cultured with cancer cells. These findings indicate that lipolytic and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid uptake by cancer cells may be a novel therapy targeting interactions between cancer and stromal cells. PMID:28407685

Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet.

PubMed

Yan, Lin; Sundaram, Sneha; Nielsen, Forrest H

2017-11-01

This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet.

aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

USDA-ARS?s Scientific Manuscript database

Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wi...

Temperature sensing of adipose tissue heating with the luminescent upconversion nanoparticles as nanothermometer: in vitro study

NASA Astrophysics Data System (ADS)

Yanina, I. Yu.; Volkova, E. K.; Zaharevich, A. M.; Konyukhova, J. G.; Kochubey, V. I.; Tuchin, V. V.

2017-03-01

The luminescence spectra of upconversion nanoparticles (UCNPs) imbedded in fat tissue were measured in a wide temperature range, from room to human body and further to hyperthermic temperatures. The two types of synthesized UCNP [NaYF4:Yb3+, Er3+] specimens, namely, powdered as-is and embedded into polymer film, were used. The results show that the luminescence of UCNPs placed under the adipose tissue layer is reasonably good sensitive to temperature change and reflects phase transitions of lipids in tissue cells. The most likely, multiple phase transitions are associated with the different components of fat cells such as phospholipids of cell membrane and lipids of fat droplets. In the course of fat cell heating, lipids of fat droplet first transit from a crystalline form to a liquid crystal form and then to a liquid form, which is characterized by much less scattering. The phase transitions of lipids were observed as the changes of the slope of the temperature dependence of UCNP luminescence intensity. The obtained results confirm a high sensitivity of the luminescent UCNPs to the temperature variations within tissues and show a strong potential for providing a controllable tissue thermolysis.

Dietary sandalwood seed oil modifies fatty acid composition of mouse adipose tissue, brain, and liver.

PubMed

Liu, Y; Longmore, R B

1997-09-01

Sandalwood (Santalum spicatum) seed oil, which occurs to about 50% of the weight of the seed kernels, contains 30-35% of total fatty acids (FA) as ximenynic acid (XMYA). This study was designed to obtain basic information on changes in tissue FA composition and on the metabolic fate of XMYA in mice fed a sandalwood seed oil (SWSO)-enriched diet. Female mice were randomly divided into three groups, each receiving different semisynthetic diets containing 5.2% (w/w) fat (standard laboratory diet), 15% canola oil, or 15% SWSO for 8 wk. The effects of SWSO as a dietary fat on the FA composition of adipose tissue, brain, and liver lipids were determined by analyses of FA methyl ester derivatives of extracted total lipid. The FA compositions of the liver and adipose tissue were markedly altered by the dietary fats, and mice fed on a SWSO-enriched diet were found to contain XMYA but only in low concentration (0.3-3%) in these tissues; XMYA was not detected in brain. Oleic acid was suggested to be a principal XMYA biotransformation product. The results were interpreted to suggest that the metabolism of XMYA may involve both biohydrogenation and oxidation reactions.

Roles of leptin in bone metabolism and bone diseases.

PubMed

Chen, Xu Xu; Yang, Tianfu

2015-09-01

Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

PubMed

Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

2018-01-01

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

[Evaluate the Efficacy of Electroacupuncture Therapy on Abdominal Fat in Obese Women by Using Magnetic Resonance Imaging].

PubMed

Lei, Hong; Chen, Xiao; Hu, Dong-Gang; Chen, Yu-Ting; Feng, Li-Cheng; Chen, Zhen-Yan; Li, Fang

2016-10-25

To evaluate the efficacy of electroacupuncture (EA) therapy on abdominal fat in obese women by using magnetic resonance imaging(MRI). Thirty abdominal obesity women patients were randomly divided into control group ( n =15) and EA group ( n =15). The obesity patients of the control group did not receive any treatment for weight reduction, and those of the EA group were treated by EA stimulation of bilateral Neiting (ST 44), Fenglong (ST 40), Zusanli (ST 36), Huaroumen (ST 24), Tianshu (ST 25), Wailing (ST 26), Shuidao (ST 28), Fujie (SP 14), Daheng (SP 13), etc. for 25 min, once every other day, 3 times per week for 3 months. The patient's body weight, height, waist circumference (WC) were mea-sured with different devices, and the body mass index (BMI) was calculated, and the subcutaneous adipose tissue thickness at the inferior edges of L 4 , L 5 and S 3 and the superior edge of the pubic symphysis and the total abdominal fat volume between the L 4 and S 3 levels were detected using MRI systems before and after the treatment. The effects of the EA group were significantly superior to those of the control group in lowering difference values (between pre- and post-treatment) of BMI, WC and subcutaneous adipose tissue thickness at the levels of the inferior edges of L 4 , L 5 , S 3 and the superior edge of the pubic symphysis(all P <0.01)and in reducing total abdominal fat volume between L 4 and S 3 (all P <0.01). After the treatment, the subcutaneous adipose tissue thickness at the superior edge of the pubic symphysis ( P <0.01) and the total abdominal fat volume between L 4 and S 3 ( P <0.05) were significantly decreased in the EA group compared to pre-treatment. There were no significant differences between post- and pre-treatment in BMI, WC, subcutaneous adipose tissue thickness at the levels of the L 4 , L 5 and S 3 in both EA and control groups and in the subcutaneous adipose tissue thickness at the level of the superior edge of the pubic symphysis and the total abdominal fat volume between L 4 and S 3 in the control group ( P >0.05). EA intervention can effectively reduce abdominal fat in obese women based on the evaluation of MRI.

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

Central Adiposity is Negatively Associated with Hippocampal-Dependent Relational Memory among Overweight and Obese Children

PubMed Central

Khan, Naiman A.; Baym, Carol L.; Monti, Jim M.; Raine, Lauren B.; Drollette, Eric S.; Scudder, Mark R.; Moore, R. Davis; Kramer, Arthur F.; Hillman, Charles H.; Cohen, Neal J.

2014-01-01

Objective To assess associations between adiposity and hippocampal-dependent and hippocampal-independent memory forms among prepubertal children. Study design Prepubertal children (7–9-year-olds, n = 126), classified as non-overweight (<85th %tile BMI-for-age [n = 73]) or overweight/obese (≥85th %tile BMI-for-age [n = 53]), completed relational (hippocampal-dependent) and item (hippocampal-independent) memory tasks, and performance was assessed with both direct (behavioral accuracy) and indirect (preferential disproportionate viewing [PDV]) measures. Adiposity (%whole body fat mass, subcutaneous abdominal adipose tissue, visceral adipose tissue, and total abdominal adipose tissue) was assessed using DXA. Backward regressions identified significant (P <0.05) predictive models of memory performance. Covariates included age, sex, pubertal timing, socioeconomic status, IQ, oxygen consumption (VO2max), and body mass index (BMI) z-score. Results Among overweight/obese children, total abdominal adipose tissue was a significant negative predictor of relational memory behavioral accuracy, and pubertal timing together with socioeconomic status jointly predicted the PDV measure of relational memory. In contrast, among non-overweight children, male sex predicted item memory behavioral accuracy, and a model consisting of socioeconomic status and BMI z-score jointly predicted the PDV measure of relational memory. Conclusions Regional, and not whole body, fat deposition was selectively and negatively associated with hippocampal-dependent relational memory among overweight/obese prepubertal children. PMID:25454939

Central adiposity is negatively associated with hippocampal-dependent relational memory among overweight and obese children.

PubMed

Khan, Naiman A; Baym, Carol L; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Scudder, Mark R; Moore, R Davis; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

2015-02-01

To assess associations between adiposity and hippocampal-dependent and hippocampal-independent memory forms among prepubertal children. Prepubertal children (age 7-9 years; n = 126), classified as non-overweight (<85th percentile body mass index [BMI]-for-age [n = 73]) or overweight/obese (≥85th percentile BMI-for-age [n = 53]), completed relational (hippocampal-dependent) and item (hippocampal-independent) memory tasks. Performance was assessed with both direct (behavioral accuracy) and indirect (preferential disproportionate viewing [PDV]) measures. Adiposity (ie, percent whole-body fat mass, subcutaneous abdominal adipose tissue, visceral adipose tissue, and total abdominal adipose tissue) was assessed by dual-energy X-ray absorptiometry. Backward regression identified significant (P < .05) predictive models of memory performance. Covariates included age, sex, pubertal timing, socioeconomic status (SES), IQ, oxygen consumption, and BMI z-score. Among overweight/obese children, total abdominal adipose tissue was a significant negative predictor of relational memory behavioral accuracy, and pubertal timing together with SES jointly predicted the PDV measure of relational memory. In contrast, among non-overweight children, male sex predicted item memory behavioral accuracy, and a model consisting of SES and BMI z-score jointly predicted the PDV measure of relational memory. Regional, but not whole-body, fat deposition was selectively and negatively associated with hippocampal-dependent relational memory among overweight/obese prepubertal children. Copyright © 2015 Elsevier Inc. All rights reserved.

Complement factor H is expressed in adipose tissue in association with insulin resistance.

PubMed

Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

2010-01-01

Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances.

Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

PubMed

Maessen, Dionne E; Brouwers, Olaf; Gaens, Katrien H; Wouters, Kristiaan; Cleutjens, Jack P; Janssen, Ben J; Miyata, Toshio; Stehouwer, Coen D; Schalkwijk, Casper G

2016-04-01

Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Measurement of Basal and Forskolin-stimulated Lipolysis in Inguinal Adipose Fat Pads.

PubMed

Baskaran, Padmamalini; Thyagarajan, Baskaran

2017-07-21

Lipolysis is a process by which the lipid stored as triglycerides in adipose tissues are hydrolyzed into glycerol and fatty acids. This article describes the method for the measurement of basal and forskolin (FSK)-stimulated lipolysis in the inguinal fat pads isolated from wild type mice fed either normal chow diet (NCD), high fat diet (HFD) or a high fat diet containing 0.01% of capsaicin (CAP; transient receptor potential vanilloid subfamily 1 (TRPV1) agonist) for 32 weeks. The method described here for performing ex vivo lipolysis is adopted from Schweiger et al. 1 We present a detailed protocol for measuring glycerol levels by UV-Visible (UV/VIS) spectrophotometry. The method described here can be used to successfully isolate inguinal fat pads for lipolysis measurements to obtain consistent results. The protocol described for inguinal fat pads can readily be extended to measure lipolysis in other tissues.

Diacylglycerol-enriched structured lipids containing CLA and capric acid alter body fat mass and lipid metabolism in rats.

PubMed

Kim, Hye-Jin; Lee, Ki-Teak; Lee, Mi-Kyung; Jeon, Seon-Min; Choi, Myung-Sook

2006-01-01

The present study compared the effect of corn oil, diacylglycerol (DG) oil, and DG-enriched structured lipids (SL-DG) produced from corn oil, capric and conjugated linoleic acid on adiposity in rats fed an AIN-76 diet (5% fat) for 6 weeks. The plasma and hepatic lipids, adipose tissue weight, and enzyme activities related to fatty acid metabolism were determined. The weights of the epididymal white adipose tissue (WAT), perirenal WAT, and interscapular WAT were significantly lower in the SL-DG group than in the DG group. Reduction of fat mass in the SL-DG group was related to suppressing fatty acid synthase activities and enhancing beta-oxidation activity in perirenal WAT. The plasma leptin was lower in the SL-DG group than in the DG group, plus a lower plasma TG level was accompanied by an increase in adipocyte LPL activity. Meanwhile the SL-DG supplement lowered the plasma and hepatic cholesterol level. In addition, the hepatic HMG-CoA reductase and ACAT activities were significantly lower in the SL-DG group than in the other groups. The DG-enriched SL used in this study was effective in enhancing triglyceride metabolism in adipose tissue, especially as regards reducing the abdominal fat mass and cholesterol metabolism in the liver. Copyright 2006 S. Karger AG, Basel.

Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

PubMed

Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hanne-Louise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul

2011-12-30

The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis.

Effects of a eucaloric reduced-carbohydrate diet on body composition and fat distribution in women with PCOS.

PubMed

Goss, Amy M; Chandler-Laney, Paula C; Ovalle, Fernando; Goree, Laura Lee; Azziz, Ricardo; Desmond, Renee A; Wright Bates, G; Gower, Barbara A

2014-10-01

To determine if consumption of a reduced-carbohydrate (CHO) diet would result in preferential loss of adipose tissue under eucaloric conditions, and whether changes in adiposity were associated with changes in postprandial insulin concentration. In a crossover-diet intervention, 30 women with PCOS consumed a reduced-CHO diet (41:19:40% energy from CHO:protein:fat) for 8 weeks and a standard diet (55:18:27) for 8 weeks. Body composition by DXA and fat distribution by CT were assessed at baseline and following each diet phase. Insulin AUC was obtained from a solid meal test (SMT) during each diet phase. Participants lost 3.7% and 2.2% total fat following the reduced-CHO diet and STD diet, resp. (p<0.05 for difference between diets). The reduced-CHO diet induced a decrease in subcutaneous-abdominal, intra-abdominal, and thigh-intermuscular adipose tissue (-7.1%, -4.6%, and -11.5%, resp.), and the STD diet induced a decrease in total lean mass. Loss of fat mass following the reduced CHO diet arm was associated with lower insulin AUC (p<0.05) during the SMT. In women with PCOS, consumption of a diet lower in CHO resulted in preferential loss of fat mass from metabolically harmful adipose depots, whereas a diet high in CHO appeared to promote repartitioning of lean mass to fat mass. Copyright © 2014 Elsevier Inc. All rights reserved.

Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes.

PubMed

Jayabalan, Nanthini; Nair, Soumyalekshmi; Nuzhat, Zarin; Rice, Gregory E; Zuñiga, Felipe A; Sobrevia, Luis; Leiva, Andrea; Sanhueza, Carlos; Gutiérrez, Jaime Agustín; Lappas, Martha; Freeman, Dilys Jane; Salomon, Carlos

2017-01-01

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body's major energy reservoir. The role of adipose tissue, however, is not restricted to a "bag of fat." The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue-derived EVs and metabolic syndrome in obesity. In this review, we will discuss the changes in human placenta and adipose tissue in GDM and obesity and summarize the findings regarding the role of adipose tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the contribution of obesity to the development of GDM.

Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes

PubMed Central

Jayabalan, Nanthini; Nair, Soumyalekshmi; Nuzhat, Zarin; Rice, Gregory E.; Zuñiga, Felipe A.; Sobrevia, Luis; Leiva, Andrea; Sanhueza, Carlos; Gutiérrez, Jaime Agustín; Lappas, Martha; Freeman, Dilys Jane; Salomon, Carlos

2017-01-01

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body’s major energy reservoir. The role of adipose tissue, however, is not restricted to a “bag of fat.” The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue-derived EVs and metabolic syndrome in obesity. In this review, we will discuss the changes in human placenta and adipose tissue in GDM and obesity and summarize the findings regarding the role of adipose tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the contribution of obesity to the development of GDM. PMID:29021781

Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity

PubMed Central

Morgan-Bathke, Maria; Chen, Liang; Oberschneider, Elisabeth; Harteneck, Debra

2015-01-01

Adipose tissue fatty acid storage varies according to sex, adipose tissue depot, and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We examined whether differences in adipose tissue glycerol-3-phosphate acyltransferase (GPAT) might play a role in these variations. We optimized an enzyme activity assay for total GPAT and GPAT1 activity in human adipose tissue and measured GPAT activity. Omental and subcutaneous adipose tissue was collected from obese and nonobese adults for measures of GPAT and GPAT1 activities, ex vivo palmitate storage, acyl-CoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT) activities, and CD36 protein. Total GPAT and GPAT1 activities decreased as a function of adipocyte size in both omental (r = −0.71, P = 0.003) and subcutaneous (r = −0.58, P = 0.04) fat. The relative contribution of GPAT1 to total GPAT activity increased as a function of adipocyte size, accounting for up to 60% of GPAT activity in those with the largest adipocytes. We found strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots (r values 0.58–0.91) and between these storage factors and palmitate storage rates into TAG (r values 0.55–0.90). We conclude that: 1) total GPAT activity decreases as a function of adipocyte size; 2) GPAT1 can account for over half of adipose GPAT activity in hypertrophic obesity; and 3) ACS, GPAT, and DGAT are coordinately regulated. PMID:25738782

Gender differences in GH response to GHRH+ARG in lipodystrophic patients with HIV: a key role for body fat distribution.

PubMed

Brigante, Giulia; Diazzi, Chiara; Ansaloni, Anna; Zirilli, Lucia; Orlando, Gabriella; Guaraldi, Giovanni; Rochira, Vincenzo

2014-05-01

Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRH+Arg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRH+Arg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Men had lower GH peak and AUC than women (P<0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak <7.5 μg/l). VAT-to-SAT ratio was higher in men than in women with GHD (P<0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P<0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. These data demonstrate that GH response to GHRH+Arg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH-IGF1 status in these patients.

Characterization of the central neural projections to brown, white, and beige adipose tissue.

PubMed

Wiedmann, Nicole M; Stefanidis, Aneta; Oldfield, Brian J

2017-11-01

The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue. © FASEB.

Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets.

PubMed

Lecomte, Manon; Couëdelo, Leslie; Meugnier, Emmanuelle; Loizon, Emmanuelle; Plaisancié, Pascale; Durand, Annie; Géloën, Alain; Joffre, Florent; Vaysse, Carole; Michalski, Marie-Caroline; Laugerette, Fabienne

2017-05-01

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods. Copyright © 2017 Elsevier Inc. All rights reserved.

Iodothyronine 5'-deiodinase activity and thyroid hormone content in brown adipose tissue during the breeding cycle of the rat.

PubMed Central

Viñas, O; Giralt, M; Obregón, M J; Iglesias, R; Villarroya, F; Mampel, T

1988-01-01

Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity levels in the latter groups. Thus an impaired response to insulin in brown fat does not appear to be a factor leading to the lowered iodothyronine 5'-deiodinase activity during late pregnancy and lactation. PMID:3060112

Automatic segmentation of abdominal organs and adipose tissue compartments in water-fat MRI: Application to weight-loss in obesity.

PubMed

Shen, Jun; Baum, Thomas; Cordes, Christian; Ott, Beate; Skurk, Thomas; Kooijman, Hendrik; Rummeny, Ernst J; Hauner, Hans; Menze, Bjoern H; Karampinos, Dimitrios C

2016-09-01

To develop a fully automatic algorithm for abdominal organs and adipose tissue compartments segmentation and to assess organ and adipose tissue volume changes in longitudinal water-fat magnetic resonance imaging (MRI) data. Axial two-point Dixon images were acquired in 20 obese women (age range 24-65, BMI 34.9±3.8kg/m(2)) before and after a four-week calorie restriction. Abdominal organs, subcutaneous adipose tissue (SAT) compartments (abdominal, anterior, posterior), SAT regions along the feet-head direction and regional visceral adipose tissue (VAT) were assessed by a fully automatic algorithm using morphological operations and a multi-atlas-based segmentation method. The accuracy of organ segmentation represented by Dice coefficients ranged from 0.672±0.155 for the pancreas to 0.943±0.023 for the liver. Abdominal SAT changes were significantly greater in the posterior than the anterior SAT compartment (-11.4%±5.1% versus -9.5%±6.3%, p<0.001). The loss of VAT that was not located around any organ (-16.1%±8.9%) was significantly greater than the loss of VAT 5cm around liver, left and right kidney, spleen, and pancreas (p<0.05). The presented fully automatic algorithm showed good performance in abdominal adipose tissue and organ segmentation, and allowed the detection of SAT and VAT subcompartments changes during weight loss. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity.

PubMed

Den Hartigh, Laura J; Omer, Mohamed; Goodspeed, Leela; Wang, Shari; Wietecha, Tomasz; O'Brien, Kevin D; Han, Chang Yeop

2017-03-01

Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary adipocytes differentiated from mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance. © 2016 American Heart Association, Inc.

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.

Sirt1 attenuates camptothecin-induced apoptosis through caspase-3 pathway in porcine preadipocytes

USDA-ARS?s Scientific Manuscript database

Adipose tissue is an important energy reservoir, and its over-development results in obesity in humans or body fat over-deposition in livestock. Loss of preadipocytes through apoptosis has been proposed as an alternative way to reduce adipose tissue mass. At present, the effect and regulatory mechan...

Dynamic M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high fat diet-induced obesity in mice

USDA-ARS?s Scientific Manuscript database

Chronic inflammation is a pathogenic factor in obesity complications, in particular insulin resistance (IR). A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been the recognition of the underlying role of adipose tissue macrophages (ATM's). The...

CDK6 inhibits white to beige fat transition by suppressing RUNX1

USDA-ARS?s Scientific Manuscript database

Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit ...

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

Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears.

PubMed

Bentzen, T W; Muir, D C G; Amstrup, S C; O'Hara, T M

2008-11-15

We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. SigmaChlordane concentrations were higher in females, and both SigmaPCBs and SigmaChlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; SigmaPCB>Sigma10PCB>PCB153>SigmaChlordane>Oxychlordane>PCB180>SigmaHCH>beta-HCH>SigmaDDT>p,p-DDE>SigmaPBDE>HCB>Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited.

Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears

USGS Publications Warehouse

Bentzen, T.W.; Muir, D.C.G.; Amstrup, Steven C.; O'Hara, T. M.

2008-01-01

We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. ??Chlordane concentrations were higher in females, and both ??PCBs and ??Chlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; ??PCB > ??10PCB > PCB153 > ??Chlordane > Oxychlordane > PCB180 > ??HCH > ??-HCH > ??DDT > p,p-DDE > ??PBDE > HCB > Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited. ?? 2008 Elsevier B.V.

Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets

PubMed Central

Shin, Sunhye

2018-01-01

Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON) or high-fat diets (HFD) containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB), olive oil (oleic acid-rich oil; OO), safflower oil (linoleic acid-rich oil; SFO), or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO) ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE) treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo. PMID:29473916

Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets.

PubMed

Shin, Sunhye; Ajuwon, Kolapo M

2018-02-23

Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON) or high-fat diets (HFD) containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB), olive oil (oleic acid-rich oil; OO), safflower oil (linoleic acid-rich oil; SFO), or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO) ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE) treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo.

Higher Natriuretic Peptide Levels Associate with a Favorable Adipose Tissue Distribution Profile

PubMed Central

Neeland, Ian J.; Winders, Benjamin R.; Ayers, Colby R.; Das, Sandeep R.; Chang, Alice Y.; Berry, Jarett D.; Khera, Amit; McGuire, Darren K.; Vega, Gloria L.; de Lemos, James A.; Turer, Aslan T.

2013-01-01

Objectives To investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models but data are lacking in humans. Methods 2619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and NT-proBNP and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results Median BNP and NT-proBNP levels in the study cohort (mean age 44 years, 56% women, 48% African-Americans, 32% obese) were 3.0 and 28.1 pg/mL, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance including lower visceral fat, liver fat, and HOMA-IR; and more lower body fat and higher adiponectin (p<0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral (β= −0.08, p<0.0001) and liver fat (β= −0.14, p<0.0001) and positively associated with lower body fat (β= 0.07, p<0.0001) independent of age, sex, race, and obesity-status; findings were similar with BNP. Adjustment for body composition, HOMA-IR, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides. PMID:23602771

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.

An automated segmentation for direct assessment of adipose tissue distribution from thoracic and abdominal Dixon-technique MR images

NASA Astrophysics Data System (ADS)

Hill, Jason E.; Fernandez-Del-Valle, Maria; Hayden, Ryan; Mitra, Sunanda

2017-02-01

Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) together have become the gold standard in the precise quantification of body fat. The study of the quantification of fat in the human body has matured in recent years from a simplistic interest in the whole-body fat content to detailing regional fat distributions. The realization that body-fat, or adipose tissue (AT) is far from being a mere aggregate mass or deposit but a biologically active organ in and of itself, may play a role in the association between obesity and the various pathologies that are the biggest health issues of our time. Furthermore, a major bottleneck in most medical image assessments of adipose tissue content and distribution is the lack of automated image analysis. This motivated us to develop a proper and at least partially automated methodology to accurately and reproducibly determine both body fat content and distribution in the human body, which is to be applied to cross-sectional and longitudinal studies. The AT considered here is located beneath the skin (subcutaneous) as well as around the internal organs and between muscles (visceral and inter-muscular). There are also special fat depots on and around the heart (pericardial) as well as around the aorta (peri-aortic). Our methods focus on measuring and classifying these various AT deposits in the human body in an intervention study that involves the acquisition of thoracic and abdominal MR images via a Dixon technique.

Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.

PubMed

Zhang, Yongxian; Gu, Jin; Wang, Lin; Zhao, Zilong; Pan, Yi; Chen, Yan

2017-01-05

Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G -/- mice compared to the wild type controls. The metabolic rate of the mice as measured by O 2 consumption and CO 2 production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Physiological regulation and metabolic role of browning in white adipose tissue.

PubMed

Jankovic, Aleksandra; Otasevic, Vesna; Stancic, Ana; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato

2017-09-01

Great progress has been made in our understanding of the browning process in white adipose tissue (WAT) in rodents. The recognition that i) adult humans have physiologically inducible brown adipose tissue (BAT) that may facilitate resistance to obesity and ii) that adult human BAT molecularly and functionally resembles beige adipose tissue in rodents, reignited optimism that obesity and obesity-related diabetes type 2 can be battled by controlling the browning of WAT. In this review the main cellular mechanisms and molecular mediators of browning of WAT in different physiological states are summarized. The relevance of browning of WAT in metabolic health is considered primarily through a modulation of biological role of fat tissue in overall metabolic homeostasis.

Metabolic characteristics of human subcutaneous abdominal adipose tissueafter overnight fast

PubMed Central

Humphreys, Sandy M.

2012-01-01

Subcutaneous abdominal adipose tissue is one of the largest fat depots and contributes the major proportion of circulating nonesterified fatty acids (NEFA). Little is known about aspects of human adipose tissue metabolism in vivo other than lipolysis. Here we collated data from 331 experiments in 255 healthy volunteers over a 23-year period, in which subcutaneous abdominal adipose tissue metabolism was studied by measurements of arterio-venous differences after an overnight fast. NEFA and glycerol were released in a ratio of 2.7:1, different (P < 0.001) from the value of 3.0 that would indicate no fatty acid re-esterification. Fatty acid re-esterification was 10.2 ± 1.4%. Extraction of triacylglycerol (TG) (fractional extraction 5.7 ± 0.4%) indicated intravascular lipolysis by lipoprotein lipase, and this contributed 21 ± 3% of the glycerol released. Glucose uptake (fractional extraction 2.6 ± 0.3%) was partitioned around 20–25% for provision of glycerol 3-phosphate and 30% into lactate production. There was release of lactate and pyruvate, with extraction of the ketone bodies 3-hydroxybutyrate and acetoacetate, although these were small numerically compared with TG and glucose uptake. NEFA release (expressed per 100 g tissue) correlated inversely with measures of fat mass (e.g., with BMI, rs = −0.24, P < 0.001). We examined within-person variability. Systemic NEFA concentrations, NEFA release, fatty acid re-esterification, and adipose tissue blood flow were all more consistent within than between individuals. This picture of human adipose tissue metabolism in the fasted state should contribute to a greater understanding of adipose tissue physiology and pathophysiology. PMID:22167523

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.

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV-infected men.

PubMed

He, Qing; Engelson, Ellen S; Ionescu, Gabriel; Glesby, Marshall J; Albu, Jeanine B; Kotler, Donald P

2008-01-01

A large proportion of HIV-infected patients on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. We performed a cross-sectional analysis of baseline data from 23 HIV-infected participants in three prospective clinical studies. Magnetic resonance spectroscopy was used to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole-body adipose tissue compartments: that is, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes, as well as the intermuscular adipose tissue (IMAT) subcompartment and the omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. The homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Hepatic lipid content correlated significantly with total VAT (r = 0.62, P = 0.0014), but not with SAT (r = 0.053, P = 0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r = 0.67, P = 0.0004) and RPAT (r = 0.53, P = 0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r = 0.61, P = 0.057 and r = 0.68, P = 0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Hepatic lipid content is associated with VAT volume, especially the OMAT subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men.

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV infected men

PubMed Central

He, Qing; Engelson, Ellen S.; Ionescu, Gabriel; Glesby, Marshall J.; Albu, Jeanine B.; Kotler, Donald P.

2010-01-01

Background A large proportion of HIV-infected subjects on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. Design and methods We performed a cross-sectional analysis of baseline data from twenty-three HIV-infected participants in 3 prospective clinical studies. Magnetic resonance spectroscopy was applied to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole body adipose tissue compartments, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes as well as inter-muscular adipose tissue (IMAT) subcompartment, and omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. Homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Results Hepatic lipid content correlated significantly with total VAT (r=0.62, p=0.0014) but not with SAT (r=0.053, p=0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r=0.67, p=0.0004) and RPAT (r=0.53, p=0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r=0.61, p=0.057 and 0.68, p=0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Conclusion Hepatic lipid content is associated with VAT volume, especially the omental-mesenteric subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men. PMID:18572755

Maternal nutrition induces gene expression changes in fetal muscle and adipose tissues in sheep.

PubMed

Peñagaricano, Francisco; Wang, Xin; Rosa, Guilherme Jm; Radunz, Amy E; Khatib, Hasan

2014-11-28

Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep. Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR ≤0.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR ≤0.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR ≤0.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes. These findings provide evidence that maternal nutrition during pregnancy can alter the programming of fetal muscle and fat tissues in sheep. The ramifications of the observed gene expression changes, in terms of postnatal growth, body composition, and meat quality of the offspring, warrant future investigation.

Green tea extract induces genes related to browning of white adipose tissue and limits weight-gain in high energy diet-fed rat.

PubMed

Chen, Li-Han; Chien, Yi-Wen; Liang, Chung-Tiang; Chan, Ching-Hung; Fan, Meng-Han; Huang, Hui-Yu

2017-01-01

Background: A wealth of research has reported on the anti-obesity effects of green tea extract (GTE). Although browning of white adipose tissue (WAT) has been reported to attenuate obesity, no study has disclosed the effects of GTE on browning in Sprague Dawley rats. Objectives: The aims of the study were to investigate the effects of GTE on anti-obesity and browning, and their underlying mechanisms. Methods: Four groups of rats (n=10/group) were used including a normal diet with vehicle treatment, and a high-energy diet (HED) with vehicle or GTE by oral gavage at 77.5 or 155 mg/kg/day for 8 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The gene expressions were analyzed using RT-qPCR and western blotting. Results: GTE modulated HED-induced body weight, fat accumulation, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein, free fatty acids, aspartate aminotransferase, and alanine aminotransferase. Moreover, GTE enhanced the serum high-density lipoprotein. Most importantly, the biomarkers of beige adipose tissue were up-regulated in WAT in GTE-given groups. GTE induced genes involved in different pathways of browning, and reduced transducin-like enhancer protein-3 in WAT. Conclusion: Our results suggest that GTE may improve obesity through inducing browning in HED-fed rats. Abbreviations : ALT: Alanine transaminase; AST: Aspartate transaminase; BAT: Brown adipose tissue; BMP-7: Bone morphogenetic protein-7; BW: Body weight; CIDEA: Cell death activator; CPT-1: Carnitine palmitoyltransferase-1; EFP: Epididymal fat pad; FFA: Free fatty acid; FGF-21: Fibroblast growth factor-21; GTE: Green tea extract; HDL: High-density lipoprotein; HED: high-energy diet; LDL: Low-density lipoprotein; MFP: Mesenteric fat pad; PGC-1α: Activates PPAR-γ coactivator-1; PPAR-γ: Peroxisome proliferator-activated receptor-γ; PRDM-16: PR domain containing 16; RFP: Renal fat pad; SD: Sprague Dawley; TC: Total cholesterol; TG: Triacylglycerol; TLE-3: Transducin-like enhancer protein-3: UCP-1: Uncoupling protein-1; WAT: White adipose tissue.

Wnt inhibition enhances browning of mouse primary white adipocytes.

PubMed

Lo, Kinyui Alice; Ng, Pei Yi; Kabiri, Zahra; Virshup, David; Sun, Lei

2016-01-01

The global epidemic in obesity and metabolic syndrome requires novel approaches to tackle. White adipose tissue, traditionally seen as a passive energy-storage organ, can be induced to take on certain characteristics of brown fat in a process called browning. The "browned" white adipose tissue, or beige fat, is a potential anti-obesity target. Various signaling pathways can enhance browning. Wnt is a key regulator of adipocyte biology, but its role in browning has not been explored. In this study, we found that in primary mouse adipocytes derived from the inguinal depot, Wnt inhibition by both chemical and genetic methods significantly enhanced browning. The effect of Wnt inhibition on browning most likely targets the beige precursor cells in selected adipose depots.

Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic outcomes and stronger intestinal barrier.

PubMed

Benoit, Bérengère; Plaisancié, Pascale; Géloën, Alain; Estienne, Monique; Debard, Cyrille; Meugnier, Emmanuelle; Loizon, Emmanuelle; Daira, Patricia; Bodennec, Jacques; Cousin, Olivier; Vidal, Hubert; Laugerette, Fabienne; Michalski, Marie-Caroline

2014-08-28

Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.

Adipose tissue dysregulation and metabolic consequences in childhood and adolescent obesity: potential impact of dietary fat quality.

PubMed

McMorrow, Aoibheann M; Connaughton, Ruth M; Lithander, Fiona E; Roche, Helen M

2015-02-01

Evidence suggests that at a population level, childhood and adolescent obesity increase the long-term risk of chronic diseases such as type 2 diabetes and CVD. At an individual level, however, the metabolic consequences of obesity in youth vary immensely. Despite comparable BMI, some adolescents develop impaired glucose tolerance while others maintain normal glucose homeostasis. It has been proposed that the variation in the capacity to store lipid in the subcutaneous adipose tissue (SAT) may partially discriminate metabolically healthy from unhealthy obesity. In positive energy balance, a decreased capacity to expand SAT may drive lipid accumulation to visceral adipose tissue, liver and skeletal muscle. This state of lipotoxicity is associated with chronic low-grade inflammation, insulin resistance and dyslipidaemia. The present review examines the differential adipose tissue development and function in children and adolescents who exhibit metabolic dysregulation compared with those who are protected. Additionally, the role of manipulating dietary fat quality to potentially prevent and treat metabolic dysfunction in obesity will be discussed. The findings of the present review highlight the need for further randomised controlled trials to establish the effect of dietary n-3 PUFA on the metabolic phenotype of obese children and adolescents. Furthermore, using a personalised nutrition approach to target interventions to those at risk of, or those with established metabolic dysregulation may optimise the efficacy of modifying dietary fat quality.

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

High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling- and inflammation-related genes.

PubMed

Choi, Myung-Sook; Kim, Young-Je; Kwon, Eun-Young; Ryoo, Jae Young; Kim, Sang Ryong; Jung, Un Ju

2015-03-28

The aim of the present study was to identify the genes differentially expressed in the visceral adipose tissue in a well-characterised mouse model of high-fat diet (HFD)-induced obesity. Male C57BL/6J mice (n 20) were fed either HFD (189 % of energy from fat) or low-fat diet (LFD, 42 % of energy from fat) for 16 weeks. HFD-fed mice exhibited obesity, insulin resistance, dyslipidaemia and adipose collagen accumulation, along with higher levels of plasma leptin, resistin and plasminogen activator inhibitor type 1, although there were no significant differences in plasma cytokine levels. Energy intake was similar in the two diet groups owing to lower food intake in the HFD group; however, energy expenditure was also lower in the HFD group than in the LFD group. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity and skeletal system development were down-regulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodelling and inflammation were up-regulated. The top ten up- or down-regulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1 and Gpnmb, whose roles in the deterioration of obesity-associated adipose tissue are poorly understood. In conclusion, the genes identified here provide new therapeutic opportunities for prevention and treatment of diet-induced obesity.

Studies in fat grafting: Part I. Effects of injection technique on in vitro fat viability and in vivo volume retention.

PubMed

Chung, Michael T; Paik, Kevin J; Atashroo, David A; Hyun, Jeong S; McArdle, Adrian; Senarath-Yapa, Kshemendra; Zielins, Elizabeth R; Tevlin, Ruth; Duldulao, Chris; Hu, Michael S; Walmsley, Graham G; Parisi-Amon, Andreina; Momeni, Arash; Rimsa, Joe R; Commons, George W; Gurtner, Geoffrey C; Wan, Derrick C; Longaker, Michael T

2014-07-01

Fat grafting has become increasingly popular for the correction of soft-tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, the authors compare the biological properties of fat following injection using two methods. Lipoaspiration samples were obtained from five female donors, and cellular viability, proliferation, and lipolysis were evaluated following injection using either a modified Coleman technique or an automated, low-shear device. Comparisons were made to minimally processed, uninjected fat. Volume retention was also measured over 12 weeks after injection of fat under the scalp of immunodeficient mice using either the modified Coleman technique or the Adipose Tissue Injector. Finally, fat grafts were analyzed histologically. Fat viability and cellular proliferation were both significantly greater with the Adipose Tissue Injector relative to injection with the modified Coleman technique. In contrast, significantly less lipolysis was noted using the automated device. In vivo fat volume retention was significantly greater than with the modified Coleman technique at the 4-, 6-, 8-, and 12-week time points. This corresponded to significantly greater histologic scores for healthy fat and lower scores for injury following injection with the device. Biological properties of injected tissues reflect how disruptive and harmful techniques for placement of fat may be, and the authors' in vitro and in vivo data both support the use of the automated, low-shear devices compared with the modified Coleman technique.

Studies in Fat Grafting: Part I. Effects of Injection Technique on in vitro Fat Viability and in vivo Volume Retention

PubMed Central

Chung, Michael T.; Paik, Kevin J.; Atashroo, David A.; Hyun, Jeong S.; McArdle, Adrian; Senarath-Yapa, Kshemendra; Zielins, Elizabeth R.; Tevlin, Ruth; Duldulao, Chris; Hu, Michael S.; Walmsley, Graham G.; Parisi-Amon, Andreina; Momeni, Arash; Rimsa, Joe R.; Commons, George W.; Gurtner, Geoffrey C.; Wan, Derrick C.; Longaker, Michael T.

2014-01-01

Background Fat grafting has become increasingly popular for the correction of soft tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, we compare the biologic properties of fat following injection using two methods. Methods Lipoaspiration samples were obtained from five female donors and cellular viability, proliferation, and lipolysis were evaluated following injection using either a modified Coleman technique or an automated, low shear device. Comparisons were made to minimally processed, uninjected fat. Volume retention was also measured over twelve weeks following injection of fat under the scalp of immunodeficient mice using either the modified Coleman technique or the Adipose Tissue Injector. Finally, fat grafts were analyzed histologically. Results Fat viability and cellular proliferation were both significantly greater with the Adipose Tissue Injector relative to injection with the modified Coleman technique. In contrast, significantly less lipolysis was noted using the automated device. In vivo fat volume retention was significantly greater than with the modified Coleman technique at 4, 6, 8, and 12 week time points. This corresponded with significantly greater histological scores for healthy fat and lower scores for injury following injection with the device. Conclusions Biological properties of injected tissues reflect how disruptive and harmful techniques for placement of fat may be, and our in vitro and in vivo data both support the use of the automated, low shear devices compared to the modified Coleman technique. PMID:24622574

Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice

PubMed Central

2012-01-01

Background Obesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR). Methods Tissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits. Results In obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice. Conclusions CR exerts distinct effects on adipocyte cytokine and angiogenesis profiles in obese and lean mice. Our study also underscores the importance of angiogenesis-related proteins and cytokines in adipose tissue remodeling and development of obesity. PMID:22748184

Adipose tissue engineering: state of the art, recent advances and innovative approaches.

PubMed

Tanzi, Maria Cristina; Farè, Silvia

2009-09-01

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

Role of fat metabolism in exercise.

PubMed

Askew, E W

1984-07-01

Fat and carbohydrate are the two major energy sources used during exercise. Either source can predominate, depending upon the duration and intensity of exercise, degree of prior physical conditioning, and the composition of the diet consumed in the days prior to a bout of exercise. Fatty acid oxidation can contribute 50 to 60 per cent of the energy expenditure during a bout of low intensity exercise of long duration. Strenuous submaximal exercise requiring 65 to 80 per cent of VO2 max will utilize less fat (10 to 45 per cent of the energy expended). Exercise training is accompanied by metabolic adaptations that occur in skeletal muscle and adipose tissue and that facilitate a greater delivery and oxidation of fatty acids during exercise. The trained state is characterized by an increased flux of fatty acids through smaller pools of adipose tissue energy. This is reflected by smaller, more metabolically active adipose cells in smaller adipose tissue depots. Peak blood concentrations of free fatty acids and ketone bodies are lower during and following exercise in trained individuals, probably due to increased capacity of the skeletal musculature to oxidize these energy sources. Trained individuals oxidize more fat and less carbohydrate than untrained subjects when performing submaximal work of the same absolute intensity. This increased capacity to utilize energy from fat conserves crucial muscle and liver glycogen stores and can contribute to increased endurance. Further benefits of the enhanced lipid metabolism accompanying chronic aerobic exercise training are decreased cardiac risk factors. Exercise training results in lower blood cholesterol and triglycerides and increased high density lipoprotein cholesterol. High-fat diets are not recommended because of their association with atherosclerotic heart disease. Recent evidence suggests that low-fat high-carbohydrate diets may increase blood triglycerides and reduce high density lipoproteins. This suggests that the chronic ingestion of diets that are extreme in their composition of either fat or carbohydrate should be approached with caution in health-conscious athletes, as well as in sedentary individuals.

Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

PubMed

Park, Ye Seul; Uddin, Md Jamal; Piao, Lingjuan; Hwang, Inah; Lee, Jung Hwa; Ha, Hunjoo

2016-01-01

Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

A mirccroarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice

USDA-ARS?s Scientific Manuscript database

Objective: A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulatio...

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.

Curcuma longa extract associated with white pepper lessens high fat diet-induced inflammation in subcutaneous adipose tissue.

PubMed

Neyrinck, Audrey M; Alligier, Maud; Memvanga, Patrick B; Névraumont, Elodie; Larondelle, Yvan; Préat, Véronique; Cani, Patrice D; Delzenne, Nathalie M

2013-01-01

Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity. Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation. These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.

Curcuma longa Extract Associated with White Pepper Lessens High Fat Diet-Induced Inflammation in Subcutaneous Adipose Tissue

PubMed Central

Memvanga, Patrick B.; Névraumont, Elodie; Larondelle, Yvan; Préat, Véronique; Cani, Patrice D.; Delzenne, Nathalie M.

2013-01-01

Background Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity. Methodology/Principal Findings Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation. Conclusions/Significance These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition. PMID:24260564

Complement Factor H Is Expressed in Adipose Tissue in Association With Insulin Resistance

PubMed Central

Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

2010-01-01

OBJECTIVE Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. RESEARCH DESIGN AND METHODS Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. RESULTS Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. CONCLUSIONS Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances. PMID:19833879

Comparison of gross body fat-water magnetic resonance imaging at 3 Tesla to dual-energy X-ray absorptiometry in obese women.

PubMed

Silver, Heidi J; Niswender, Kevin D; Kullberg, Joel; Berglund, Johan; Johansson, Lars; Bruvold, Morten; Avison, Malcolm J; Welch, E Brian

2013-04-01

Improved understanding of how depot-specific adipose tissue mass predisposes to obesity-related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three-dimensional (3D) contiguous "fat-water" MR imaging (FWMRI) covering the majority of a whole-body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type, and distribution of adipose and lean soft tissue would show great promise in body composition methodology. Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to dual-energy X-ray absorptiometry (DXA). Anthropometric, FWMRI, and DXA measurements were obtained in 12 women with BMI 30-39.9 kg/m(2) . Test-retest results found coefficients of variation (CV) for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST, and TTLST, respectively. While Bland-Altman plots demonstrated agreement between FWMRI and DXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully-automated segmentation is fast (<30-min total scan and post-processing time), noninvasive, repeatable, and cost-effective. Copyright © 2012 The Obesity Society.

Authentication of meat products: determination of animal feeding by parallel GC-MS analysis of three adipose tissues.

PubMed

Sivadier, Guilhem; Ratel, Jérémy; Bouvier, Frédéric; Engel, Erwan

2008-11-12

Authentication of farm animal rearing conditions, especially the type of feeding, is a key issue in certification of meat quality and meat products. The purpose of this article was to analyze in parallel the volatile fraction of three adipose tissues excised from 16 lambs in order to authenticate two animal diets: pasture (n = 8) and concentrate (n = 8). On the basis of growth rate and anatomical location, three different lamb adipose tissues were analyzed: perirenal fat (PRF), caudal subcutaneous fat (CSCF), and heart fat (HF). An initial experiment was used to optimize the extraction of volatile compounds from the adipose tissues. Using a lipid liquid phase extraction, heating the ground tissue to 70 degrees C, was shown to be the best sample preparation mode before dynamic headspace-gas chromatography-mass spectrometry (DH-GC-MS) analysis to achieve a good representation of the starting material, while getting a good extraction and reproducibility. Next, the application of an instrumental drifts correction procedure to DH-GC-MS data enabled the identification of 130 volatile compounds that discriminate the two diets in one or several of the three tissues: 104 were found in PRF, 75 in CSCF, and 70 in HF. Forty-eight of these diet tracers, including 2,3-octanedione, toluene, terpenes, alkanes, alkenes, and ketones, had previously been identified as ruminant pasture-diet tracers and can be considered generic of this type of animal feeding. Moreover, 49 of the 130 compounds could identify diets in only one tissue, suggesting that complementary analysis of several tissues is superior for diet identification. Finally, multivariate discriminant analyses confirmed that the discrimination was improved when PRF, CSCF, and HF were considered simultaneously, even if HF contributed minimal information.

Visualized macrophage dynamics and significance of S100A8 in obese fat

PubMed Central

Sekimoto, Ryohei; Fukuda, Shiro; Maeda, Norikazu; Tsushima, Yu; Matsuda, Keisuke; Mori, Takuya; Nakatsuji, Hideaki; Nishizawa, Hitoshi; Kishida, Ken; Kikuta, Junichi; Maijima, Yumiko; Funahashi, Tohru; Ishii, Masaru; Shimomura, Iichiro

2015-01-01

Chronic low-grade inflammation of adipose tissue plays a crucial role in the pathophysiology of obesity. Immunohistological microscopic analysis in obese fat tissue has demonstrated the infiltration of several immune cells such as macrophages, but dynamics of immune cells have not been fully elucidated and clarified. Here, by using intravital multiphoton imaging technique, to our knowledge for the first time, we analyzed and visualized the inflammatory processes in adipose tissue under high-fat and high-sucrose (HF/HS) diet with lysozyme M-EGFP transgenic (LysMEGFP) mice whose EGFP was specifically expressed in the myelomonocytic lineage. Mobility of LysMEGFP-positive macrophages was shown to be activated just 5 d after HF/HS diet, when the distinct hypertrophy of adipocytes and the accumulation of macrophages still have not become prominent. Significant increase of S100A8 was detected in mature adipocyte fraction just 5 d after HF/HS diet. Recombinant S100A8 protein stimulated chemotactic migration in vitro and in vivo, as well as induced proinflammatory molecules, both macrophages and adipocytes, such as TNF-α and chemokine (C-C motif) ligand 2. Finally, an antibody against S100A8 efficiently suppressed the HF/HS diet-induced initial inflammatory change, i.e., increased mobilization of adipose LysMEGFP-positive macrophages, and ameliorated HF/HS diet-induced insulin resistance. In conclusion, time-lapse intravital multiphoton imaging of adipose tissues identified the very early event exhibiting increased mobility of macrophages, which may be triggered by increased expression of adipose S100A8 and results in progression of chronic inflammation in situ. PMID:25848057

Further factors influencing N-nitrosamine formation in bacon.

PubMed

Gray, J I; Skrypec, D J; Mandagere, A K; Booren, A M; Pearson, A M

1984-01-01

The possible relationship of unsaturated fatty acids in adipose tissue to the formation of N-nitrosamines in bacon was evaluated by trials in which pigs were fed regular (control), tallow-, coconut fat- and corn oil-supplemented diets. Bacon prepared from pigs fed corn oil-supplemented diets contained significantly higher levels of N-nitrosopyrrolidine and N-nitrosodimethylamine than did control bacon samples; however, bacon produced from pigs fed a coconut fat-supplemented diet contained significantly lower levels of N-nitrosopyrrolidine. Fatty acid analyses of the adipose tissue of the bacon samples indicated that N-nitrosopyrrolidine levels in bacon correlated well with the degree of unsaturation of the adipose tissue. N-nitrosothiazolidine was detected in both brine-cured and dry-cured bacon at levels generally below 4 micrograms/kg. However, its formation was greatly reduced by the inclusion of alpha-tocopherol in the cure. The role of woodsmoke in N-nitrosothiazolidine formation in bacon is discussed.

5-Aminoimidazole-4-carboxamide ribonucleotide prevents fat gain following the cessation of voluntary physical activity.

PubMed

Ruegsegger, Gregory N; Sevage, Joseph A; Childs, Thomas E; Grigsby, Kolter B; Booth, Frank W

2017-11-01

What is the central question of this study? We investigated whether 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) could prevent acute increases in body fat and changes in omental and subcutaneous adipose tissue following the sudden transition from physical activity to physical inactivity. What is the main finding and its importance? AICAR prevented fat gains following the transition from physical activity to inactivity to levels comparable to rats that remained physically active. AICAR and continuous physical activity produced depot-specific changes in cyclin A1 mRNA and protein that were associated with the prevention of fat gain. These findings suggest that targeting AMP-activated protein kinase signalling could oppose rapid adipose mass growth. The transition from physical activity to inactivity is associated with drastic increases in 'catch-up' fat that in turn foster the development of many obesity-associated maladies. We tested whether 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) treatment would prevent gains in body fat following the sudden transition from a physically active state to an inactive state by locking a voluntary running wheel. Male Wistar rats were either sedentary (SED) or given wheel access for 4 weeks, at which time rats with wheels continued running (RUN), had their wheel locked (WL) or had WL with daily AICAR injection (WL + AICAR) for 1 week. RUN and WL + AICAR prevented gains in body fat compared with SED and WL (P < 0.001). Cyclin A1 mRNA, a marker of cell proliferation, was decreased in omental, but not subcutaneous adipose tissue, in RUN and WL + AICAR compared with SED and WL groups (P < 0.05). Both cyclin A1 mRNA and protein were positively associated with gains in fat mass (P < 0.05). Cyclin A1 mRNA in omental, but not subcutaneous, adipose tissue was negatively correlated with p-AMPK levels (P < 0.05). Differences in fat gain and omental mRNA and protein levels were independent of changes in food intake and in differences in select hypothalamic mRNAs. These findings suggest that AICAR treatment prevents acute gains in adipose tissue following physical inactivity to levels of rats that continuously run, and that together, continuous physical activity and AICAR could, at least initially in these conditions, exert similar inhibitory effects on adipogenesis in a depot-specific manner. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Obesity, insulin resistance and comorbidities – Mechanisms of association

PubMed Central

Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.

2015-01-01

Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442

Gene expression in WAT from healthy humans and monkeys correlates with FGF21-induced browning of WAT in mice.

PubMed

Schlessinger, Karni; Li, Wenyu; Tan, Yejun; Liu, Franklin; Souza, Sandra C; Tozzo, Effie; Liu, Kevin; Thompson, John R; Wang, Liangsu; Muise, Eric S

2015-09-01

Identify a gene expression signature in white adipose tissue (WAT) that reports on WAT browning and is associated with a healthy phenotype. RNA from several different adipose depots across three species were analyzed by whole transcriptome profiling, including 1) mouse subcutaneous white fat, brown fat, and white fat after in vivo treatment with FGF21; 2) human subcutaneous and omental fat from insulin-sensitive and insulin-resistant patients; and 3) rhesus monkey subcutaneous fat from healthy and dysmetabolic individuals. A "browning" signature in mice was identified by cross-referencing the FGF21-induced signature in WAT with the brown adipose tissue (BAT) vs. WAT comparison. In addition, gene expression levels in WAT from insulin-sensitive/healthy vs. insulin-resistant/dysmetabolic humans and rhesus monkeys, respectively, correlated with the gene expression levels in mouse BAT vs. WAT. A subset of 49 genes were identified that were consistently regulated or differentially expressed in the mouse and human data sets that could be used to monitor browning of WAT across species. Gene expression profiles of WATs from healthy insulin-sensitive individuals correlate with those of BAT and FGF21-induced browning of WAT. © 2015 The Obesity Society.

Impact of extra-articular pathologies on groin pain: An arthroscopic evaluation.

PubMed

Kaya, Mitsunori

2018-01-01

For patients who have anterior hip pain evaluated by Patrick's test and tenderness at Scarpa's triangle, we perform periarticular debridement based on the hypothesis that extra-articular pathologies are responsible for the hip pain. The purpose of this study was to categorize the endoscopic extra-articular findings and to evaluate the clinical significance of periarticular pathologies in anterior hip pain. Arthroscopic findings of 77 patients who underwent periarthritic debridement were evaluated. As extra-articular pathologies, injuries of the direct head and reflective head of the rectus femoris muscle were evaluated. A thin layer of fat tissue normally exists on the anterior inferior iliac spine (AIIS), the attachment site of the direct head of the rectus femoris muscle. The macroscopic appearance of the fat pad on the AIIS was categorized as normal, blood vessel-rich adipose tissue or adipose tissue with fibrosis or scar formation and histologically confirmed. Adhesion of gluteal muscles to the joint capsule was also evaluated. Of the 77 patients, 75 had rupture of the direct head of the rectus femoris. In contrast, rupture of the reflective head was extremely rare. Seven patients had a normal fat pad on the AIIS, 11 had blood vessel-rich adipose tissue and 55 had adipose tissue with fibrosis. Fat tissue was completely replaced by fibrous scar tissue in another 4 patients. In 64 patients, adhesion between the anterior joint capsule and gluteus muscles was marked. Groin pain disappeared soon after the operation even when labral tears were not repaired and all patients returned to daily life and sports activities within 2 weeks after operation. Rectus femoris tendinosis, fibrosis of the AIIS fat pad, and adhesion of gluteal and rectus femoris muscles are common extra-articular pathologies in patients with anterior hip pain. Management of only these lesions induces rapid relief of anterior hip pain even in the absence of labral tear repair. My observations suggest that it is desirable to be aware of the presence of periarticular pathologies as a cause of groin pain.

Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis

PubMed Central

Li, Naisi; Yang, Qiyuan; Walker, Ryan G.; Thompson, Thomas B.; Du, Min

2016-01-01

A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn−/− (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn−/− BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn−/− animals results from nutrient partitioning away from fat and in support of muscle. PMID:26580671

Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis.

PubMed

Li, Naisi; Yang, Qiyuan; Walker, Ryan G; Thompson, Thomas B; Du, Min; Rodgers, Buel D

2016-01-01

A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle.

Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide.

PubMed

Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

2015-12-01

Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes. Copyright © 2015. Published by Elsevier B.V.

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.

Metabolic and adipose tissue signatures in adults with Prader-Willi syndrome: a model of extreme adiposity.

PubMed

Lacroix, Delphine; Moutel, Sandrine; Coupaye, Muriel; Huvenne, Hélène; Faucher, Pauline; Pelloux, Véronique; Rouault, Christine; Bastard, Jean-Philippe; Cagnard, Nicolas; Dubern, Béatrice; Clément, Karine; Poitou, Christine

2015-03-01

Prader-Willi syndrome (PWS), the most frequent syndrome of obesity, is a model of early fat mass (FM) development, but scarce data exist on adipose tissue characteristics. The objective of the study was to compare metabolic, fat distribution, and transcriptomic signatures of sc adipose tissue (scAT) in PWS adults, with matched obese adults with primary obesities. Hormonal and metabolic assessments, systemic inflammation, and gene expression in scAT were compared between PWS patients and obese controls (OCs). Each 42nd PWS patient was matched with one randomly paired control with primary obesity. Matching factors were age, gender, fat mass (percentage), and diabetic status. Compared with OCs, the PWS group had a decreased percentage of trunk FM and a better metabolic profile with decreased insulin and homeostasis model assessment, an index of insulin-resistance, and increased concentrations of serum adiponectin and ghrelin. Adipocyte size relative to body fat was significantly higher in PWS vs OCs. scAT in PWS patients was characterized by a transcriptomic functional signature with enrichment of themes related to immunoinflammation, the extracellular matrix, and angiogenesis. A RT-PCR targeted study revealed that candidate genes encoding proinflammatory markers and remodeling molecules, CD68, CD3e, IL-1β, chemokine (C-C motif) ligand 5, collagen type 4-α, and lysyl oxidase, were down-regulated. Matched for FM, PWS subjects have a better metabolic profile, a phenotype that could be linked to changes in scAT remodeling and promotion of adipocyte growth.

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

PubMed

Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2016-06-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio. Copyright © 2016 the American Physiological Society.

Association between vitamin D metabolites in fat tissue and serum 25-hydroxy vitamin D in overweight and obese adults

USDA-ARS?s Scientific Manuscript database

Cholecalciferol has been measured in human white adipose tissue (WAT), but little is known about the relationship between the other circulating vitamin D metabolites and WAT. We measured concentrations of 25(OH)D and 1,25(OH)2D in subcutaneous fat tissue from 20 overweight and obese subjects partic...

Serum CETP concentration is not associated with measures of body fat: The NEO study.

PubMed

Blauw, Lisanne L; de Mutsert, Renée; Lamb, Hildo J; de Roos, Albert; Rosendaal, Frits R; Jukema, J Wouter; Wang, Yanan; van Dijk, Ko Willems; Rensen, Patrick C N

2016-03-01

Adipose tissue has been postulated to contribute substantially to the serum cholesteryl ester transfer protein (CETP) pool. However, in a recent large cohort study waist circumference was not associated with plasma CETP. The aim of the present study was to further examine associations of accurate measures of body fat and body fat distribution with serum CETP concentration. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, we examined in 6606 participants (aged 45-65 years) the associations of total body fat, body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), abdominal subcutaneous (aSAT) and visceral adipose tissue (VAT) assessed with magnetic resonance imaging (n = 2547) and total and trunk fat mass assessed with dual-energy X-ray absorptiometry (n = 909) with serum CETP concentration. Regression models were adjusted for age, ethnicity, sex, dietary intake of fat and cholesterol, physical activity, smoking and menopausal status. Mean (SD) age was 56 (6) years and BMI 26.3 (4.4) kg/m(2), 56% were women. Mean serum CETP concentration was 2.47 μg/mL. The difference in serum CETP was 0.02 μg/mL (95%CI: -0.01, 0.05) per SD total body fat (8.7%), and 0.02 μg/mL (0.00, 0.04) per SD BMI (4.4 kg/m(2)). Similar associations around the null were observed for waist circumference, WHR, aSAT, VAT, total and trunk fat mass. In this population-based study, there was no evidence for clinically relevant associations between several measures of body fat and serum CETP concentration. This finding implies that adipose tissue does not contribute to the CETP pool in serum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Omija fruit ethanol extract improves adiposity and related metabolic disturbances in mice fed a high-fat diet.

PubMed

Park, Hyo Jin; Kim, Hye-Jin; Kim, Sang Ryong; Choi, Myung-Sook; Jung, Un Ju

2017-03-01

This study investigated the biological and molecular mechanisms underlying the antiobesity effect of omija fruit ethanol extract (OFE) in mice fed a high-fat diet (HFD). C57BL/6J mice were fed an HFD (20% fat, w/w) with or without OFE (500 mg/kg body weight) for 16 weeks. Dietary OFE significantly increased brown adipose tissue weight and energy expenditure while concomitantly decreasing white adipose tissue (WAT) weight and adipocyte size by up-regulating the expression of brown fat-selective genes in WAT. OFE also improved hepatic steatosis and dyslipidemia by enhancing hepatic fatty acid oxidation-related enzymes activity and fecal lipid excretion. In addition to steatosis, OFE decreased the expression of pro-inflammatory genes in the liver. Moreover, OFE improved glucose tolerance and lowered plasma glucose, insulin and homeostasis model assessment of insulin resistance, which may be linked to decreases in the activity of hepatic gluconeogenic enzymes and the circulating level of gastric inhibitory polypeptide. These findings suggest that OFE may protect against diet-induced adiposity and related metabolic disturbances by controlling brown-like transformation of WAT, fatty acid oxidation, inflammation in the liver and fecal lipid excretion. Improved insulin resistance may be also associated with its antiobesity effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study

PubMed Central

Van Loan, Marta D.; Keim, Nancy L.; Adams, Sean H.; Souza, Elaine; Woodhouse, Leslie R.; Thomas, Anthony; Witbracht, Megan; Gertz, Erik R.; Piccolo, Brian; Bremer, Andrew A.; Spurlock, Michael

2011-01-01

Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered. PMID:21941636

Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting.

PubMed

Hatting, Maximilian; Rines, Amy K; Luo, Chi; Tabata, Mitsuhisa; Sharabi, Kfir; Hall, Jessica A; Verdeguer, Francisco; Trautwein, Christian; Puigserver, Pere

2017-02-07

A promising approach to treating obesity is to increase diet-induced thermogenesis in brown adipose tissue (BAT), but the regulation of this process remains unclear. Here we find that CDC-like kinase 2 (CLK2) is expressed in BAT and upregulated upon refeeding. Mice lacking CLK2 in adipose tissue exhibit exacerbated obesity and decreased energy expenditure during high-fat diet intermittent fasting. Additionally, tissue oxygen consumption and protein levels of UCP1 are reduced in CLK2-deficient BAT. Phosphorylation of CREB, a transcriptional activator of UCP1, is markedly decreased in BAT cells lacking CLK2 due to enhanced CREB dephosphorylation. Mechanistically, CREB dephosphorylation is rescued by the inhibition of PP2A, a phosphatase that targets CREB. Our results suggest that CLK2 is a regulatory component of diet-induced thermogenesis in BAT through increased CREB-dependent expression of UCP1. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

Serum Glycated Albumin Is Inversely Influenced by Fat Mass and Visceral Adipose Tissue in Chinese with Normal Glucose Tolerance

PubMed Central

Hao, Yaping; Yang, Rong; Ni, Jie; Xiao, Yunfeng; Tang, Junling; Bao, Yuqian; Jia, Weiping

2012-01-01

Background Recent studies have revealed that body mass index (BMI) inversely influenced serum glycated albumin (GA), which may cause an underestimation of GA-monitored short-term hyperglycemic control. Objective This study was to investigate the association between anthropometric variables (BMI and waist circumference (W)) and accurate adiposity variables (percentage of body fat (%fat), fat mass, free fat mass (FFM), subcutaneous fat area (SFA), and visceral fat area (VFA)) with serum GA. Design A total of 2563 subjects (1037 men, 593 premenopausal women, and 933 postmenopausal women) with normal glucose tolerance underwent bioelectrical impedance body fat content measurement and magnetic resonance imaging. Serum GA and absolute value of GA (aGA) were measured by enzymatic assay. Results Compared to the BMI <25.0 kg/m2 group, the BMI ≥25.0 kg/m2 group had significantly higher fasting plasma glucose, glycated hemoglobin A1c, and body fat parameters including W, %fat, fat mass, FFM, SFA, and VFA, but significantly lower aGA, and GA in all the three sex- and menopause-stratified groups (all P<0.05). GA decreased with the increment of fat mass for all three groups (all P for trend <0.001). In the same BMI category, men and postmenopausal women with elevated %fat (men, ≥25%; women, ≥35%) still had significantly lower GA than those with normal %fat (men, <25%; women, <35%) (all P<0.05). Multiple stepwise regression showed that %fat, fat mass, and VFA were independently associated with GA. Conclusions Serum GA was inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance. PMID:23209844

Expression profiles and associations of adiponectin and adiponectin receptors with intramuscular fat in Tibetan chicken.

PubMed

Zhang, R; Lin, Y; Zhi, L; Liao, H; Zuo, L; Li, Z; Xu, Y

2017-04-01

1. Adiponectin and its receptors (ADIPOR1 and ADIPOR2) are novel endocrine systems that act at various levels to modulate glucose and lipid metabolism. This study was designed to investigate the spatial expression of adiponectin, ADIPOR1 and ADIPOR2 genes in various tissues in Tibetan chicken. The temporal expression of adiponectin and its receptor mRNAs were also studied in adipose tissue, breast muscle and thigh muscle and the correlations of the levels of adiponectin, ADIPOR1 and ADIPOR2 mRNA with the contents of intramuscular fat in breast muscle and thigh muscle of Tibetan chicken were determined. 2. Quantitative real-time PCR detected chicken adiponectin, ADIPOR1 and ADIPOR2 mRNA transcripts in heart, liver, spleen, lung, kidney, skeletal muscle and adipose tissue. 3. Adipose tissue contained the highest amount of adiponectin mRNA followed by the kidney and liver. The expression levels of ADIPOR1 mRNA were significantly higher in adipose tissue, lung and spleen, and adipose tissue exhibited significantly higher levels of ADIPOR2 mRNA followed by the spleen and lung compared with other tissues. 4. Temporal expression profiles of adiponectin, ADIPOR1 and ADIPOR2 mRNA showed gender differences in adipose tissue and skeletal muscle at certain ages. In adipose tissue, adiponectin mRNA was higher in 154-d-old females and ADIPOR1 mRNA was higher in 154-d-old males: Adiponectin and ADIPOR2 mRNA were higher, and ADIPOR1 mRNA was lower, in thigh muscle in female compared with male chickens. 5. The correlation data showed that, except for adiponectin mRNA, the levels of ADIPOR1 and ADIPOR2 mRNA in thigh muscle of males were significantly positively correlated with IMF (r = 0.206 for the ADIPOR1 gene and r = 0.676 for the ADIPOR2 gene). 6. Taken together, it was concluded that adiponectin and the ADIPOR1 and ADIPOR2 genes are ubiquitously expressed in various tissues of Tibetan chicken and the expression of the adiponectin system is gender-dependant at certain ages in adipose tissue and skeletal muscle.

Adipose tissue: cell heterogeneity and functional diversity.

PubMed

Esteve Ràfols, Montserrat

2014-02-01

There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Metabolism of sex steroids is influenced by acquired adiposity-A study of young adult male monozygotic twin pairs.

PubMed

Vihma, Veera; Naukkarinen, Jussi; Turpeinen, Ursula; Hämäläinen, Esa; Kaprio, Jaakko; Rissanen, Aila; Heinonen, Sini; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Mikkola, Tomi S; Tikkanen, Matti J; Pietiläinen, Kirsi H

2017-09-01

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22-36kg/m 2 ] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m 2 ]. Sex steroid concentrations were determined by liquid chromatography-tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI=5.9kg/m 2 ), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs. 2.4 (1.0) nmol/l, P=0.040] and mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) higher in the heavier compared to the leaner co-twins. Serum free 17β-estradiol (E2) was higher [2.3 (0.5) vs. 1.9 (0.5) pmol/l, P=0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs. 90 (22) pmol/l, P=0.006; and 123 (43) vs. 105 (27) pmol/l, P=0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations (P<0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG (P<0.05), and 3) liver fat with SHBG (P=0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2, HSD11B1, and aromatase in adipose tissue (P<0.05). In conclusion, acquired adiposity was associated with decreased serum DHT and increased estrogen concentrations, independent of genetic factors and age. The reduction of DHT could be linked to its increased degradation (by AKR1C2 and HSD11B1) and increased estrogen levels to increased adiposity-related expression of aromatase in adipose tissue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fibroblast Growth Factor 23 is Associated With Adiposity in Patients Receiving Hemodialysis: Possible Cross Talk Between Bone and Adipose Tissue.

PubMed

Chiang, Janet M; Kaysen, George A; Schafer, Anne L; Delgado, Cynthia; Johansen, Kirsten L

2018-03-29

Fibroblast growth factor 23 (FGF-23) may be involved in signaling between bone and adipose tissue in dialysis patients, but its role is uncertain. We sought to examine the association between FGF-23 and adiposity and whether this association is mediated in part by leptin. We performed univariate and multivariate linear regression analyses using data from 611 participants in a cohort of prevalent hemodialysis patients recruited from dialysis centers in Atlanta, GA and San Francisco, CA from 2009 to 2011. We also investigated the role of leptin in these relationships. Participants were aged ≥18 years, English or Spanish speaking, and receiving hemodialysis for at least 3 months. Outcome measures of adiposity included body mass index, waist circumference, and body fat measured by bioelectrical impedance spectroscopy. Mean age was 56 ± 14 years, 39.8% were female, and median serum FGF-23 was 807 pg/mL. In fully adjusted models, FGF-23 was inversely associated with body mass index (-0.24 kg/m 2 per 50% higher FGF-23, 95% confidence interval [CI]: -0.38 to -0.10), waist circumference (-0.44 cm per 50% higher FGF-23, 95% CI: -0.79 to -0.08), and percent body fat (-0.58% per 50% higher FGF-23, 95% CI: -0.79 to -0.37). Leptin was inversely associated with FGF-23. Addition of leptin to body composition models attenuated the associations between FGF-23 and measures of adiposity, but FGF-23 remained significantly associated with percent body fat (-0.17% per 50% higher FGF-23, 95% CI: -0.32 to -0.02). We found a negative association between FGF-23 and adiposity that appears to be mediated in part by leptin. As adipose tissue provides a "protective energy depot" for patients with chronic illness, a decrease in adipose tissue may be one mechanism in which higher FGF-23 levels may contribute to increased mortality in dialysis patients. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running

PubMed Central

Toedebusch, Ryan G.; Roberts, Christian K.; Roberts, Michael D.; Booth, Frank W.

2015-01-01

In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex ‘omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10–11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life. PMID:26678390

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

PubMed

Ruegsegger, Gregory N; Company, Joseph M; Toedebusch, Ryan G; Roberts, Christian K; Roberts, Michael D; Booth, Frank W

2015-01-01

In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study.

PubMed

Thamer, Claus; Machann, Jürgen; Stefan, Norbert; Schäfer, Silke A; Machicao, Fausto; Staiger, Harald; Laakso, Markku; Böttcher, Michael; Claussen, Claus; Schick, Fritz; Fritsche, Andreas; Haring, Hans-Ulrich

2008-04-01

We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e. rs1053049, rs6902123, and rs2267668, affect the improvement of mitochondrial function, aerobic physical fitness, and insulin sensitivity by lifestyle intervention (LI). The objective of the study was to determine whether the aforementioned PPARD SNPs influence the change in body composition and ectopic fat storage during LI. A total of 156 subjects at an increased risk for type 2 diabetes were genotyped for rs1053049, rs6902123, and rs2267668 and participated in a LI program. Body fat depots, ectopic liver fat, and muscle volume of the leg were quantified using magnetic resonance spectroscopy and imaging. With regard to body composition, carriers of the minor SNP alleles displayed reduced responses to LI, i.e. LI-induced reduction in adipose tissue mass (nonvisceral adipose tissue: rs1053049, P = 0.02; rs2267668, P = 0.04; visceral adipose tissue: rs1053049, P = 0.01) and hepatic lipids (rs1053049, P = 0.04; rs6902123, P = 0.001; independent of changes in adiposity) as well as LI-induced increase in relative muscle volume of the leg (rs1053049, P = 0.003; rs2267668, P = 0.009) were less pronounced in homo- and heterozygous carriers of the minor alleles as compared with homozygous carriers of the major alleles. SNPs rs1053049, rs6902123, and rs2267668 in PPARD affect LI-induced changes in overall adiposity, hepatic fat storage, and relative muscle mass. Our findings provide a mechanistic explanation for the involvement of these genetic variations in the development of insulin resistance and type 2 diabetes.

Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans.

PubMed

Matsushita, M; Yoneshiro, T; Aita, S; Kameya, T; Sugie, H; Saito, M

2014-06-01

Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. Some clinical studies have reported an association between BAT and blood glucose in humans. To examine the impact of BAT on glucose metabolism, independent of that of body fatness, age and sex in healthy adult humans. Two hundred and sixty healthy volunteers (184 males and 76 females, 20-72 years old) underwent fluorodeoxyglucose-positron emission tomography and computed tomography after 2 h of cold exposure to assess maximal BAT activity. Blood parameters including glucose, HbA1c and low-density lipoprotein (LDL)/high-density lipoprotein-cholesterol were measured by conventional methods, and body fatness was estimated from body mass index (BMI), body fat mass and abdominal fat area. The impact of BAT on body fatness and blood parameters was determined by logistic regression with the use of univariate and multivariate models. Cold-activated BAT was detected in 125 (48%) out of 260 subjects. When compared with subjects without detectable BAT, those with detectable BAT were younger and showed lower adiposity-related parameters such as the BMI, body fat mass and abdominal fat area. Although blood parameters were within the normal range in the two subject groups, HbA1c, total cholesterol and LDL-cholesterol were significantly lower in the BAT-positive group. Blood glucose also tended to be lower in the BAT-positive group. Logistic regression demonstrated that BAT, in addition to age and sex, was independently associated with BMI, body fat mass, and abdominal visceral and subcutaneous fat areas. For blood parameters, multivariate analysis after adjustment for age, sex and body fatness revealed that BAT was a significantly independent determinant of glucose and HbA1c. BAT, independent of age, sex and body fatness, has a significant impact on glucose metabolism in adult healthy humans.

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

PubMed Central

2011-01-01

Background Menopause is associated with increased adiposity, especially increased deposition of intra-abdominal (IA) adipose tissue (AT). This differs from common or 'dietary' obesity, i.e., obesity apparently due to environmentally stimulated overeating, in which IAAT and subcutaneous (S) AT increase in similar proportions. The effect of menopause on adiposity is thought to be due to the decreased secretion of ovarian estrogens. Ovariectomy in rats and other animals is a commonly used model of menopause. It is well known that ovariectomy increases adiposity and that this can be reversed by estradiol treatment, but whether ovariectomy selectively increases IAAT has not been measured directly. Therefore, we used micro-computed tomography (microCT) to investigate this question in both chow-fed and dietary-obese rats. Methods Ovariectomized, ovariectomized and estradiol treated, and sham-operated (intact) rats were fed chow or chow plus Ensure (Abbott Nutrition; n = 7/group). Total (T) AT, IAAT and SAT were measured periodically by microCT. Regional distribution of AT was expressed as IAAT as a percentage of TAT (%IAAT). Excesses in these measures were calculated with respect to chow-fed intact rats to control for normal maturational changes. Chemical analysis of fat was done in chow-fed intact and ovariectomized rats at study end. Data were analyzed by t-tests and planned comparisons. Results Body mass, TAT, total fat mass, fat-free body mass, and %IAAT all increased in chow-fed intact rats during the 41 d study. In chow-fed rats, ovariectomy increased excess body mass, TAT, fat mass, fat-free body mass, and SAT, but had little effect on IAAT, in chow-fed rats, leading to a decrease in %IAAT. Ensure feeding markedly increased SAT, IAAT and TAT and did not significantly affect %IAAT. Ovariectomy had similar effects in Ensure-fed rats as in chow-fed rats, although less statistically reliable. Estradiol treatment prevented all the effects of ovariectomy. Conclusions Both ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases. PMID:21569336

Inhibition of lipolysis in the novel transgenic quail model overexpressing G0/G1 switch gene 2 in the adipose tissue during feed restriction.

PubMed

Shin, Sangsu; Choi, Young Min; Han, Jae Yong; Lee, Kichoon

2014-01-01

In addition to the issue of obesity in humans, the production of low-fat meat from domestic animals is important in the agricultural industry to satisfy consumer demand. Understanding the regulation of lipolysis in adipose tissue could advance our knowledge to potentially solve both issues. Although the G0/G1 switch gene 2 (G0S2) was recently identified as an inhibitor of adipose triglyceride lipase (ATGL) in vitro, its role in vivo has not been fully clarified. This study was conducted to investigate the role of G0S2 gene in vivo by using two independent transgenic quail lines during different energy conditions. Unexpectedly, G0S2 overexpression had a negligible effect on plasma NEFA concentration, fat cell size and fat pad weight under ad libitum feeding condition when adipose lipolytic activity is minimal. A two-week feed restriction in non-transgenic quail expectedly caused increased plasma NEFA concentration and dramatically reduced fat cell size and fat pad weight. Contrary, G0S2 overexpression under a feed restriction resulted in a significantly less elevation of plasma NEFA concentration and smaller reductions in fat pad weights and fat cell size compared to non-transgenic quail, demonstrating inhibition of lipolysis and resistance to loss of fat by G0S2. Excessive G0S2 inhibits lipolysis in vivo during active lipolytic conditions, such as food restriction and fasting, suggesting G0S2 as a potential target for treatment of obesity. In addition, transgenic quail are novel models for studying lipid metabolism and mechanisms of obesity.

Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer.

PubMed

Wang, Yuan-Yuan; Lehuédé, Camille; Laurent, Victor; Dirat, Béatrice; Dauvillier, Stéphanie; Bochet, Ludivine; Le Gonidec, Sophie; Escourrou, Ghislaine; Valet, Philippe; Muller, Catherine

2012-11-28

Among the many different cell types surrounding breast cancer cells, the most abundant are those that compose mammary adipose tissue, mainly mature adipocytes and progenitors. New accumulating recent evidences bring the tumor-surrounding adipose tissue into the light as a key component of breast cancer progression. The purpose of this review is to emphasize the role that adipose tissue might play by locally affecting breast cancer cell behavior and subsequent clinical consequences arising from this dialog. Two particular clinical aspects are addressed: obesity that was identified as an independent negative prognostic factor in breast cancer and the oncological safety of autologous fat transfer used in reconstructive surgery for breast cancer patients. This is preceded by the overall description of adipose tissue composition and function with special emphasis on the specificity of adipose depots and the species differences, key experimental aspects that need to be taken in account when cancer is considered. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of dual-energy X-ray absorptiometry and magnetic resonance imaging-measured adipose tissue depots in HIV-infected and control subjects.

PubMed

Scherzer, Rebecca; Shen, Wei; Bacchetti, Peter; Kotler, Donald; Lewis, Cora E; Shlipak, Michael G; Punyanitya, Mark; Heymsfield, Steven B; Grunfeld, Carl

2008-10-01

Studies in persons without HIV infection have compared adipose tissue measured by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI), but no such study has been conducted in HIV-infected (HIV+) subjects, who have a high prevalence of regional fat loss. We compared DXA- with MRI-measured trunk, leg, arm, and total fat in HIV+ and control subjects. A cross-sectional analysis was conducted in 877 HIV+ subjects and 260 control subjects in FRAM (Study of Fat Redistribution and Metabolic Change in HIV Infection), stratified by sex and HIV status. Univariate associations of DXA with MRI were strongest for total and trunk fat (r > or = 0.92) and slightly weaker for leg (r > or = 0.87) and arm (r > or = 0.71) fat. The average estimated limb fat was substantially greater for DXA than for MRI for HIV+ and control men and women (all P < 0.0001). Less of a difference was observed in trunk fat measured by DXA and MRI, but the difference was still statistically significant (P < 0.0001). Bland-Altman plots showed increasing differences and variability. Greater average limb fat in control and HIV+ subjects (both P < 0.0001) was associated with greater differences between DXA and MRI measurements. Because the control subjects had more limb fat than did the HIV+ subjects, greater amounts of fat were measured by DXA than by MRI when control subjects were compared with HIV+ subjects. More HIV+ subjects had leg fat in the bottom decile of the control subjects by DXA than by MRI (P < 0.0001). Although DXA- and MRI-measured adipose tissue depots correlate strongly in HIV+ and control subjects, differences increase as average fat increases, particularly for limb fat. DXA may estimate a higher prevalence of peripheral lipoatrophy than does MRI in HIV+ subjects.

N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer.

PubMed

Ouldamer, Lobna; Goupille, Caroline; Vildé, Anne; Arbion, Flavie; Body, Gilles; Chevalier, Stephan; Cottier, Jean Philippe; Bougnoux, Philippe

2016-01-01

The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality. Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality. We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality. These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.

Loss of body weight and fat and improved lipid profiles in obese rats fed apple pomace or apple juice concentrate.

PubMed

Cho, Kyung-Dong; Han, Chan-Kyu; Lee, Bog-Hieu

2013-09-01

The purpose of this study was to investigate the influence of apple pomace (AP) and apple juice concentrate (AC) supplementation on body weight and fat loss as well as lipid metabolism in obese rats fed a high-fat diet. Diet-induced obese rats were assigned to three groups (n=8 for each group): high fat diet (HFD) control, HFD containing 10% (w/w) AP, and HFD containing 10% (w/w) AC. There was also a normal diet group (n=8). After 5 weeks, body weight gain, adipose tissue weight, serum and hepatic lipid profiles, liver morphology, and adipocyte size were measured. Body weight gain, white adipose tissue (WAT) weight, serum total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations, epididymal adipocyte size, and lesion scores were significantly lower and serum high-density lipoprotein cholesterol concentration and brown adipose tissue weights were significantly higher in the AP and AC groups compared with the HFD group. In addition, atherogenic indices in the AP and AC groups were significantly lower than in the HFD group. These results indicate that supplementing apple products such as AP and AC may help suppress body weight and WAT gain, as well as improve lipid profiles in diet-induced obese rats.

Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages.

PubMed

Tarabra, Elena; An Lee, Ting-Wen; Zammit, Victor A; Vatish, Manu; Yamada, Eijiro; Pessin, Jeffrey E; Bastie, Claire C

2017-10-17

Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency ( fynKO ) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.

Loss of Body Weight and Fat and Improved Lipid Profiles in Obese Rats Fed Apple Pomace or Apple Juice Concentrate

PubMed Central

Cho, Kyung-Dong; Han, Chan-Kyu

2013-01-01

Abstract The purpose of this study was to investigate the influence of apple pomace (AP) and apple juice concentrate (AC) supplementation on body weight and fat loss as well as lipid metabolism in obese rats fed a high-fat diet. Diet-induced obese rats were assigned to three groups (n=8 for each group): high fat diet (HFD) control, HFD containing 10% (w/w) AP, and HFD containing 10% (w/w) AC. There was also a normal diet group (n=8). After 5 weeks, body weight gain, adipose tissue weight, serum and hepatic lipid profiles, liver morphology, and adipocyte size were measured. Body weight gain, white adipose tissue (WAT) weight, serum total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations, epididymal adipocyte size, and lesion scores were significantly lower and serum high-density lipoprotein cholesterol concentration and brown adipose tissue weights were significantly higher in the AP and AC groups compared with the HFD group. In addition, atherogenic indices in the AP and AC groups were significantly lower than in the HFD group. These results indicate that supplementing apple products such as AP and AC may help suppress body weight and WAT gain, as well as improve lipid profiles in diet-induced obese rats. PMID:23909905

Anti-obesity and anti-diabetic effects of ethanol extract of Artemisia princeps in C57BL/6 mice fed a high-fat diet.

PubMed

Yamamoto, Norio; Kanemoto, Yuki; Ueda, Manabu; Kawasaki, Kengo; Fukuda, Itsuko; Ashida, Hitoshi

2011-01-01

Artemisia princeps is commonly used as a food ingredient and in traditional Asian medicine. In this study, we examined the effects of long-term administration of an ethanol extract of A. princeps (APE) on body weight, white adipose tissue, blood glucose, insulin, plasma and hepatic lipids, and adipocytokines in C57BL/6 mice fed a high-fat diet. Daily feeding of a 1% APE diet for 14 weeks normalized elevated body weight, white adipose tissue, and plasma glucose and insulin levels, and delayed impaired glucose tolerance in mice a fed high-fat diet. These events were not observed in mice fed a control diet containing 1% APE. Liver triglyceride and cholesterol levels were similar in mice fed a 1% APE-diet and those fed a control diet. In the high-fat diet groups, APE inhibited hepatic fatty acid synthase (FAS) and suppressed the elevation of plasma leptin, but had no effect on adiponectin levels. These findings suggest that the regulation of leptin secretion by APE may inhibit FAS activity with subsequent suppression of triglyceride accumulation in the liver and adipose tissues. Inhibition of lipid accumulation can, in turn, lead to improvements in impaired glucose tolerance.

Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis12

PubMed Central

Okla, Meshail; Kim, Jiyoung

2017-01-01

Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes. Despite advances in knowledge regarding the developmental lineage and transcriptional regulators of brown and beige adipocytes, our current understanding of environmental modifiers of BAT thermogenesis, such as diet, is limited. In this review, we consolidated the latest research on dietary molecules that may serve to promote BAT thermogenesis. Here, we summarized the thermogenic function of selected phytochemicals (e.g., capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids (e.g., fish oil and conjugated linoleic acids), and all-trans retinoic acid, a vitamin A metabolite. We also delineated the proposed mechanisms whereby these dietary molecules promote BAT activity and/or browning of white adipose tissue. Characterizing thermogenic dietary factors may offer novel insight into revising nutritional intervention strategies aimed at obesity and diabetes prevention and management. PMID:28507012

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

PubMed

Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice

PubMed Central

Powner, Michael B.; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of “whitening” of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. PMID:26226015

Characterization of In Vitro Engineered Human Adipose Tissues: Relevant Adipokine Secretion and Impact of TNF-α

PubMed Central

Aubin, Kim; Safoine, Meryem; Proulx, Maryse; Audet-Casgrain, Marie-Alice; Côté, Jean-François; Têtu, Félix-André; Roy, Alphonse; Fradette, Julie

2015-01-01

Representative modelling of human adipose tissue functions is central to metabolic research. Tridimensional models able to recreate human adipogenesis in a physiological tissue-like context in vitro are still scarce. We describe the engineering of white adipose tissues reconstructed from their cultured adipose-derived stromal precursor cells. We hypothesize that these reconstructed tissues can recapitulate key functions of AT under basal and pro-inflammatory conditions. These tissues, featuring human adipocytes surrounded by stroma, were stable and metabolically active in long-term cultures (at least 11 weeks). Secretion of major adipokines and growth factors by the reconstructed tissues was determined and compared to media conditioned by human native fat explants. Interestingly, the secretory profiles of the reconstructed adipose tissues indicated an abundant production of leptin, PAI-1 and angiopoietin-1 proteins, while higher HGF levels were detected for the human fat explants. We next demonstrated the responsiveness of the tissues to the pro-inflammatory stimulus TNF-α, as reflected by modulation of MCP-1, NGF and HGF secretion, while VEGF and leptin protein expression did not vary. TNF-α exposure induced changes in gene expression for adipocyte metabolism-associated mRNAs such as SLC2A4, FASN and LIPE, as well as for genes implicated in NF-κB activation. Finally, this model was customized to feature adipocytes representative of progressive stages of differentiation, thereby allowing investigations using newly differentiated or more mature adipocytes. In conclusion, we produced tridimensional tissues engineered in vitro that are able to recapitulate key characteristics of subcutaneous white adipose tissue. These tissues are produced from human cells and their neo-synthesized matrix elements without exogenous or synthetic biomaterials. Therefore, they represent unique tools to investigate the effects of pharmacologically active products on human stromal cells, extracellular matrix and differentiated adipocytes, in addition to compounds modulating adipogenesis from precursor cells. PMID:26367137

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.

Identification and characterization of long non-coding RNAs in subcutaneous adipose tissue from castrated and intact full-sib pair Huainan male pigs

USDA-ARS?s Scientific Manuscript database

Testosterone deficiency is associated with obesity in humans. It has been proven that long non-coding RNAs (lncRNAs) regulate adipose tissue metabolism; therefore, we first study the role of lncRNAs on testosterone deficiency-induced fat deposition using castrated male pigs as the model animal. The ...

Isoliquiritigenin Attenuates Adipose Tissue Inflammation in vitro and Adipose Tissue Fibrosis through Inhibition of Innate Immune Responses in Mice.

PubMed

Watanabe, Yasuharu; Nagai, Yoshinori; Honda, Hiroe; Okamoto, Naoki; Yamamoto, Seiji; Hamashima, Takeru; Ishii, Yoko; Tanaka, Miyako; Suganami, Takayoshi; Sasahara, Masakiyo; Miyake, Kensuke; Takatsu, Kiyoshi

2016-03-15

Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides the inflammasome in adipose tissue inflammation is unknown. We here show that ILG suppresses adipose tissue inflammation by affecting the paracrine loop containing saturated fatty acids and TNF-α by using a co-culture composed of adipocytes and macrophages. ILG suppressed inflammatory changes induced by the co-culture through inhibition of NF-κB activation. This effect was independent of either inhibition of inflammasome activation or activation of peroxisome proliferator-activated receptor-γ. Moreover, ILG suppressed TNF-α-induced activation of adipocytes, coincident with inhibition of IκBα phosphorylation. Additionally, TNF-α-mediated inhibition of Akt phosphorylation under insulin signaling was alleviated by ILG in adipocytes. ILG suppressed palmitic acid-induced activation of macrophages, with decreasing the level of phosphorylated Jnk expression. Intriguingly, ILG improved high fat diet-induced fibrosis in adipose tissue in vivo. Finally, ILG inhibited TLR4- or Mincle-stimulated expression of fibrosis-related genes in stromal vascular fraction from obese adipose tissue and macrophages in vitro. Thus, ILG can suppress adipose tissue inflammation by both inflammasome-dependent and -independent manners and attenuate adipose tissue fibrosis by targeting innate immune sensors.

Zinc Deficiency Augments Leptin Production and Exacerbates Macrophage Infiltration into Adipose Tissue in Mice Fed a High-Fat Diet123

PubMed Central

Liu, Ming-Jie; Bao, Shengying; Bolin, Eric R.; Burris, Dara L.; Xu, Xiaohua; Sun, Qinghua; Killilea, David W.; Shen, Qiwen; Ziouzenkova, Ouliana; Belury, Martha A.; Failla, Mark L.; Knoell, Daren L.

2013-01-01

Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5–1.5 mg/kg), we investigated whether Zn deficiency exacerbates the extent of adiposity as well as perturbations in metabolic and immune function. C57BL/6 mice were randomly assigned to receive either a high-fat diet (HFD) or a control (C) diet for 6 wk, followed by further subdivision into 2 additional groups fed Zn-deficient diets (C-Zn, HFD-Zn), along with a C diet and an HFD, for 3 wk (n = 8–9 mice/group). The extent of visceral fat, insulin resistance, or systemic inflammation was unaffected by Zn deficiency. Strikingly, Zn deficiency significantly augmented circulating leptin concentrations (HFD-Zn vs. HFD: 3.15 ± 0.16 vs. 2.59 ± 0.12 μg/L, respectively) and leptin signaling in the liver of obese mice. Furthermore, gene expression of macrophage-specific markers ADAM8 (A disintegrin and metalloproteinase domain-containing protein 8) and CD68 (cluster of differentiation 68) was significantly greater in adipose tissue in the HFD-Zn group than in the HFD group, as confirmed by CD68 protein analysis, indicative of increased macrophage infiltration. Inspection of Zn content and mRNA profiles of all Zn transporters in the adipose tissue revealed alterations of Zn metabolism to obesity and Zn deficiency. Our results demonstrate that Zn deficiency increases leptin production and exacerbates macrophage infiltration into adipose tissue in obese mice, indicating the importance of Zn in metabolic and immune dysregulation in obesity. PMID:23700340

Women With Gestational Diabetes Mellitus Randomized to a Higher-Complex Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance, Inflammation, Glucose, and Free Fatty Acids: A Pilot Study.

PubMed

Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A; Reece, Melanie S; Reynolds, Regina M; de la Houssaye, Becky A; Heerwagen, Margaret; Donahoo, William T; Daniels, Linda J; Chartier-Logan, Catherine; Janssen, Rachel C; Friedman, Jacob E; Barbour, Linda A

2016-01-01

Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher-complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE (10.1 ± 1.4 vs. 12.6 ± 2%, respectively). A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

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

Fujii, Masakazu, E-mail: masakazu731079@yahoo.co.jp; Inoguchi, Toyoshi, E-mail: toyoshi@intmed3.med.kyushu-u.ac.jp; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophagemore » polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.« less

Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

PubMed

Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

2007-02-13

Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.

Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome.

PubMed

Torriani, Martin; Fitch, Kathleen; Stavrou, Eleni; Bredella, Miriam A; Lim, Ruth; Sass, Christina A; Cypess, Aaron M; Grinspoon, Steven

2012-04-01

The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in lipodystrophic HIV and healthy control subjects. Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [¹⁸F]FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. Mean standardized uptake value of [¹⁸F]FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r² = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure.

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.

Extra-Virgin Olive Oil with Natural Phenolic Content Exerts an Anti-Inflammatory Effect in Adipose Tissue and Attenuates the Severity of Atherosclerotic Lesions in Ldlr-/-.Leiden Mice.

PubMed

Luque-Sierra, Amparo; Alvarez-Amor, Leticia; Kleemann, Robert; Martín, Franz; Varela, Lourdes M

2018-05-15

The present study investigates the effect of olive oils with different phenolic content in high-fat diets (HFDs) on hypertrophy and inflammation in adipose tissue and associated atherosclerosis, in the context of obesity. Ldlr-/-.Leiden mice were fed three different HFDs for 32 weeks and were compared with mice fed the standard low-fat diet (LFD). The different fats provided in the HFDs were lard (HFD-L), extra-virgin olive oil (EVOO; 79 mg kg -1 of phenolic compounds, HFD-EVOO), or EVOO rich in phenolic compounds (OL, 444 mg kg -1 of phenolic compounds, HFD-OL). All HFD-fed mice became obese, but only HFD-L-induced adipocyte hypertrophy. HFD-EVOO mice exhibited the greatest levels of Adiponectin in adipose tissue and presented atherosclerotic lesions similar to the LFD group, with a very low count of monocyte/macrophage compared with HFD-L and HFD-OL mice. Enrichment of the phenolic content of olive oil reduced the secretion of nitrites/nitrates in the aorta, but atherosclerosis was not attenuated in HFD-OL mice compared to other HFD mice. Consumption of olive oil with a natural content of phenolic compounds attenuates adipose tissue hypertrophy and inflammation and exerts antiatherosclerotic effects in mice. A higher phenolic content of olive oil did not provide further benefits in the prevention of atherosclerosis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Energy metabolism in feasting and fasting.

PubMed

Owen, O E; Reichard, G A; Patel, M S; Boden, G

1979-01-01

During feasting on a balanced carbohydrate, fat, and protein meal resting metabolic rate, body temperature and respiratory quotient all increase. The dietary components are utilized to replenish and augment glycogen and fat stores in the body. Excessive carbohydrate is also converted to lipid in the liver and stored along with the excessive lipids of dietary origin as triglycerides in adipose tissue, the major fuel storage depot. Amino acids in excess of those needed for protein synthesis are preferentially catabolized over glucose and fat for energy production. This occurs because there are no significant storage sites for amino acids or proteins, and the accumulation of nitrogenous compounds is ill tolerated. During fasting, adipose tissue, muscle, liver, and kidneys work in concert to supply, to convert, and to conserve fuels for the body. During the brief postabsorptive period, blood fuel homeostasis is maintained primarily by hepatic glycogenolysis and adipose tissue lipolysis. As fasting progresses, muscle proteolysis supplies glycogenic amino acids for heightened hepatic gluconeogenesis for a short period of time. After about three days of starvation, the metabolic profile is set to conserve protein and to supply greater quantities of alternate fuels. In particular, free fatty acids and ketone bodies are utilized to maintain energy needs. The ability of the kidney to conserve ketone bodies prevents the loss of large quantities of these valuable fuels in the urine. This delicate interplay among liver, muscle, kidney, and adipose tissue maintains blood fuel homeostasis and allows humans to survive caloric deprivation for extended periods.

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.

Effect of body condition on tissue distribution of perfluoroalkyl substances (PFASs) in Arctic fox (Vulpes lagopus).

PubMed

Aas, Camilla Bakken; Fuglei, Eva; Herzke, Dorte; Yoccoz, Nigel G; Routti, Heli

2014-10-07

Arctic animals undergo large seasonal fluctuations in body weight. The effect of body condition on the distribution and composition of 16 perfluoroalkyl substances (PFASs) was investigated in liver, blood, kidney, adipose tissue, and muscle of Arctic foxes (Vulpes lagopus) from Svalbard (n = 18, age 1-3 years). PFAS concentrations were generally highest in liver, followed by blood and kidney, while lowest concentrations were found in adipose tissue and muscle. Concentrations of summed perfluorocarboxylic acids and perfluoroalkyl sulfonates were five and seven times higher, respectively, in adipose tissue of lean compared to fat foxes. In addition, perfluorodecanoate (PFDA) and perfluoroheptanesulfonate (PFHpS) concentrations in liver, kidney, and blood, and, perfluorononanoate (PFNA) in liver and blood, were twice as high in the lean compared to the fat foxes. The ratio between perfluorooctane sulfonamide (FOSA) and its metabolite perfluorooctanesulfonate (PFOS) was lowest in liver, muscle, and kidney, while significantly higher proportions of FOSA were found in adipose tissue and blood. The results of the present study suggest that toxic potential of exposure to PFAS among other pollutants in Arctic mammals may increase during seasonal emaciation. The results also suggest that body condition should be taken into account when assessing temporal trends of PFASs.

Metabolic syndrome and inflammation in adipose tissue occur at different times in animals submitted to a high-sugar/fat diet.

PubMed

Francisqueti, Fabiane Valentini; Nascimento, André Ferreira; Minatel, Igor Otávio; Dias, Marcos Correa; Luvizotto, Renata de Azevedo Melo; Berchieri-Ronchi, Carolina; Ferreira, Ana Lúcia A; Corrêa, Camila Renata

2017-01-01

Obesity is associated with low-grade inflammation, triggered in adipose tissue, which may occur due to an excess of SFA from the diet that can be recognised by Toll-like receptor-4. This condition is involved in the development of components of the metabolic syndrome associated with obesity, especially insulin resistance. The aim of the study was to evaluate the manifestation of the metabolic syndrome and adipose tissue inflammation as a function of the period of time in which rats were submitted to a high-sugar/fat diet (HSF). Male Wistar rats were divided into six groups to receive the control diet (C) or the HSF for 6, 12 or 24 weeks. HSF increased the adiposity index in all HSF groups compared with the C group. HSF was associated with higher plasma TAG, glucose, insulin and leptin levels. Homeostasis model assessment increased in HSF compared with C rats at 24 weeks. Both TNF-α and IL-6 were elevated in the epididymal adipose tissue of HSF rats at 24 weeks compared with HSF at 6 weeks and C at 24 weeks. Only the HSF group at 24 weeks showed increased expression of both Toll-like receptor-4 and NF-κB. More inflammatory cells were found in the HSF group at 24 weeks. We can conclude that the metabolic syndrome occurs independently of the inflammatory response in adipose tissue and that inflammation is associated with hypertrophy of adipocytes, which varies according to duration of exposure to the HSF.

Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.

PubMed

Gandhi, Gopalsamy Rajiv; Jothi, Gnanasekaran; Antony, Poovathumkal James; Balakrishna, Kedike; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Stalin, Antony; Al-Dhabi, Naif Abdullah

2014-12-15

In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

PubMed

Shamansurova, Zulaykho; Tan, Paul; Ahmed, Basma; Pepin, Emilie; Seda, Ondrej; Lavoie, Julie L

2016-10-01

We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα

PubMed Central

Yan, Ming; Audet-Walsh, Étienne; Manteghi, Sanaz; Dufour, Catherine Rosa; Walker, Benjamin; Baba, Masaya; St-Pierre, Julie; Giguère, Vincent; Pause, Arnim

2016-01-01

The tumor suppressor folliculin (FLCN) forms a repressor complex with AMP-activated protein kinase (AMPK). Given that AMPK is a master regulator of cellular energy homeostasis, we generated an adipose-specific Flcn (Adipoq-FLCN) knockout mouse model to investigate the role of FLCN in energy metabolism. We show that loss of FLCN results in a complete metabolic reprogramming of adipose tissues, resulting in enhanced oxidative metabolism. Adipoq-FLCN knockout mice exhibit increased energy expenditure and are protected from high-fat diet (HFD)-induced obesity. Importantly, FLCN ablation leads to chronic hyperactivation of AMPK, which in turns induces and activates two key transcriptional regulators of cellular metabolism, proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) and estrogen-related receptor α (ERRα). Together, the AMPK/PGC-1α/ERRα molecular axis positively modulates the expression of metabolic genes to promote mitochondrial biogenesis and activity. In addition, mitochondrial uncoupling proteins as well as other markers of brown fat are up-regulated in both white and brown FLCN-null adipose tissues, underlying the increased resistance of Adipoq-FLCN knockout mice to cold exposure. These findings identify a key role of FLCN as a negative regulator of mitochondrial function and identify a novel molecular pathway involved in the browning of white adipocytes and the activity of brown fat. PMID:27151976

Bardoxolone methyl prevents fat deposition and inflammation in the visceral fat of mice fed a high-fat diet.

PubMed

Dinh, Chi H L; Szabo, Alexander; Camer, Danielle; Yu, Yinghua; Wang, Hongqin; Huang, Xu-Feng

2015-03-05

Key features of diet-induced obesity are visceral fat deposition, macrophage infiltration and inflammation that can lead to metabolic disorders. This study examined the effects of bardoxolone methyl (BARD) in preventing obesity and inflammation in the visceral fat of mice fed high-fat diet. Male C57BL/6J mice were fed a high-fat diet (HFD), a low-fat diet (LFD, i.e., lab chow diet) or a high-fat diet supplemented with BARD (HFD/BARD) for 21weeks. BARD at a dosage of 10mg/kg body weight was administered orally in drinking water. Histology, immunohistochemistry and Western blot were used for the analysis of epididymal adipose tissue. Morphological results demonstrated that HFD fed mice treated with BARD had smaller adipocytes and fewer macrophages present in epididymal adipose tissue than the HFD group. Furthermore, BARD administration reduced the inflammatory profile in this tissue by increasing the expression of nuclear factor of kappa-light-polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) protein and decreasing the protein expression of tumour necrosis factor alpha (TNF-α). BARD also prevented oxidative stress reflected by a reduction in stress activated proteins, including signal transducer and activator of transcription 3 (STAT3), protein kinase B (Akt), extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). BARD administration activated the sympathetic nervous system in epididymal adipose tissue assessed by the increased synthesis of tyrosine hydroxylase (TH) and uncoupling protein 2 (UCP2). The expression of inflammatory and sympathetic nervous system proteins in BARD mice fed a HFD was equivalent to that of the LFD control mice, indicating the anti-inflammatory and anti-obesity properties of this drug. In conclusion, the oral administration of BARD in HFD mice prevented fat deposition, inflammation and oxidative stress, and improved sympathetic activity in visceral fat. This study suggests a potential therapeutic role of BARD in preventing the development of obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Validation of a free software for unsupervised assessment of abdominal fat in MRI.

PubMed

Maddalo, Michele; Zorza, Ivan; Zubani, Stefano; Nocivelli, Giorgio; Calandra, Giulio; Soldini, Pierantonio; Mascaro, Lorella; Maroldi, Roberto

2017-05-01

To demonstrate the accuracy of an unsupervised (fully automated) software for fat segmentation in magnetic resonance imaging. The proposed software is a freeware solution developed in ImageJ that enables the quantification of metabolically different adipose tissues in large cohort studies. The lumbar part of the abdomen (19cm in craniocaudal direction, centered in L3) of eleven healthy volunteers (age range: 21-46years, BMI range: 21.7-31.6kg/m 2 ) was examined in a breath hold on expiration with a GE T1 Dixon sequence. Single-slice and volumetric data were considered for each subject. The results of the visceral and subcutaneous adipose tissue assessments obtained by the unsupervised software were compared to supervised segmentations of reference. The associated statistical analysis included Pearson correlations, Bland-Altman plots and volumetric differences (VD % ). Values calculated by the unsupervised software significantly correlated with corresponding supervised segmentations of reference for both subcutaneous adipose tissue - SAT (R=0.9996, p<0.001) and visceral adipose tissue - VAT (R=0.995, p<0.001). Bland-Altman plots showed the absence of systematic errors and a limited spread of the differences. In the single-slice analysis, VD % were (1.6±2.9)% for SAT and (4.9±6.9)% for VAT. In the volumetric analysis, VD % were (1.3±0.9)% for SAT and (2.9±2.7)% for VAT. The developed software is capable of segmenting the metabolically different adipose tissues with a high degree of accuracy. This free add-on software for ImageJ can easily have a widespread and enable large-scale population studies regarding the adipose tissue and its related diseases. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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.

Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress

PubMed Central

Wollny, Damian; Clark, Rod J.; Roopra, Avtar; Colman, Ricki J.; MacDougald, Ormond A.; Shedd, Timothy A.; Nelson, David W.; Yen, Mei-I; Yen, Chi-Liang Eric; Alexander, Caroline M.

2014-01-01

Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology. PMID:25101993

Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness.

PubMed

Arpaci, Dilek; Gurkan Tocoglu, Aysel; Yilmaz, Sabiye; Korkmaz, Sumeyye; Ergenc, Hasan; Gunduz, Huseyin; Keser, Nurgul; Tamer, Ali

2016-03-01

Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values < 0.01). However, both groups had similar EAT thickness (P = 0.532), which was positively correlated with BMI, fat mass, WC, HC, VAAT thickness, abdominal subcutaneous adipose tissue thickness, and serum triglyceride (TG) level (all P values < 0.01). We found no correlation between EAT thickness and thyroid-stimulating hormone (TSH) level, free thyroxine (FT4) level, or low-density lipoprotein-cholesterol (LDL-C) level, and anti-TPO level (all P values > 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to perform.

Plasma and white adipose tissue lipid composition in marmots.

PubMed

Florant, G L; Nuttle, L C; Mullinex, D E; Rintoul, D A

1990-05-01

White adipose tissue biopsies and plasma samples were obtained from hibernating yellow-bellied marmots (Marmota flaviventris) maintained in the laboratory. In addition, biopsies and plasma samples were obtained from normothermic animals in the field and laboratory. Measurement of plasma free fatty acid (FA) levels indicated that winter laboratory animals exhibited increased lipolysis. Additionally, analysis of white adipose tissue triacylglycerol revealed that the FA composition of the storage fat in animals maintained on the standard laboratory diet is remarkably simple and uniform between different adipose depots in the same animal. Three FAs (palmitic, oleic, and linoleic acids) made up greater than 95% of the total. Triene (alpha-linolenate) was found in newly captured animals, but the percentage of this FA decreased rapidly when the animals were maintained on the standard laboratory diet. Throughout the hibernation season (October to April), white adipose tissue-saturated FA percentage decreased, monoene percentage remained constant, and diene percentage increased. Analysis of plasma FA composition suggested that these animals tended to metabolize saturated FAs from stored lipid during hibernation and that dienes were mobilized briefly after the last arousal from hibernation in spring. From these observations, we hypothesize that marmots preferentially metabolize saturated fats during the hibernation period and that essential FAs of the omega 6 series tend to be metabolized more slowly than other FAs. These characteristics suggest that marmots are a valuable animal model in which to study lipid metabolism.

Unconventional microarray design reveals the response to obesity is largely tissue specific: analysis of common and divergent responses to diet-induced obesity in insulin-sensitive tissues.

PubMed

Lee, Robyn K; Hittel, Dustin S; Nyamandi, Vongai Z; Kang, Li; Soh, Jung; Sensen, Christoph W; Shearer, Jane

2012-04-01

Obesity is a chronic condition involving the excessive accumulation of adipose tissue that adversely affects all systems in the body. The aim of the present study was to employ an unbiased, genome-wide assessment of transcript abundance in order to identify common gene expression pathways within insulin-sensitive tissues in response to dietary-induced diabetes. Following 20 weeks of chow or high-fat feeding (60% kcal), age-matched mice underwent a euglycemic-hyperinsulinemic clamp to assess insulin sensitivity. High-fat-fed animals were obese and highly insulin resistant, disposing of ∼75% less glucose compared with their chow-fed counterparts. Tissues were collected, and gene expression was examined by microarray in 4 tissues known to exhibit obesity-related metabolic disturbances: white adipose tissue, skeletal muscle, liver, and heart. A total of 463 genes were differentially expressed between diets. Analysis of individual tissues showed skeletal muscle to exhibit the largest number of differentially expressed genes (191) in response to high-fat feeding, followed by adipose tissue (169), liver (115), and heart (65). Analyses revealed that the response of individual genes to obesity is distinct and largely tissue specific, with less than 10% of transcripts being shared among tissues. Although transcripts are largely tissue specific, a systems approach shows numerous commonly activated pathways, including those involved in signal transduction, inflammation, oxidative stress, substrate transport, and metabolism. This suggests a coordinated attempt by tissues to limit metabolic perturbations occurring in early-stage obesity. Many identified genes were associated with a variety of disorders, thereby serving as potential links between obesity and its related health risks.

Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNFα enhances GPR84 expression in adipocytes.

PubMed

Nagasaki, Hiroshi; Kondo, Takaaki; Fuchigami, Masahiro; Hashimoto, Hiroyuki; Sugimura, Yoshihisa; Ozaki, Nobuaki; Arima, Hiroshi; Ota, Akira; Oiso, Yutaka; Hamada, Yoji

2012-02-17

In this study we aimed to identify the physiological roles of G protein-coupled receptor 84 (GPR84) in adipose tissue, together with medium-chain fatty acids (MCFAs), the specific ligands for GPR84. In mice, high-fat diet up-regulated GPR84 expression in fat pads. In 3T3-L1 adipocytes, co-culture with a macrophage cell line, RAW264, or TNFα remarkably enhanced GPR84 expression. In the presence of TNFα, MCFAs down-regulated adiponectin mRNA expression in 3T3-L1 adipocytes. Taken together, our results suggest that GPR84 emerges in adipocytes in response to TNFα from infiltrating macrophages and exacerbates the vicious cycle between adiposity and diabesity. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones

PubMed Central

Chao, Lily; Marcus-Samuels, Bernice; Mason, Mark M.; Moitra, Jaideep; Vinson, Charles; Arioglu, Elif; Gavrilova, Oksana; Reitman, Marc L.

2000-01-01

There is uncertainty about the site(s) of action of the antidiabetic thiazolidinediones (TZDs). These drugs are agonist ligands of the transcription factor PPARγ, which is abundant in adipose tissue but is normally present at very low levels in liver and muscle. We have studied the effects of TZDs in A-ZIP/F-1 mice, which lack white adipose tissue. The A-ZIP/F-1 phenotype strikingly resembles that of humans with severe lipoatrophic diabetes, including the lack of fat, marked insulin resistance and hyperglycemia, hyperlipidemia, and fatty liver. Rosiglitazone or troglitazone treatment did not reduce glucose or insulin levels, suggesting that white adipose tissue is required for the antidiabetic effects of TZDs. However, TZD treatment was effective in lowering circulating triglycerides and increasing whole body fatty acid oxidation in the A-ZIP/F-1 mice, indicating that this effect occurs via targets other than white adipose tissue. A-ZIP/F-1 mice have markedly increased liver PPARγ mRNA levels, which may be a general property of fatty livers. Rosiglitazone treatment increased the triglyceride content of the steatotic livers of A-ZIP/F-1 and ob/ob mice, but not the “lean” livers of fat-transplanted A-ZIP/F-1 mice. In light of this evidence that rosiglitazone acts differently in steatotic livers, the effects of rosiglitazone, particularly on hepatic triglyceride levels, should be examined in humans with hepatic steatosis. PMID:11086023

Biological effects of low frequency high intensity ultrasound application on ex vivo human adipose tissue.

PubMed

Palumbo, P; Cinque, B; Miconi, G; La Torre, C; Zoccali, G; Vrentzos, N; Vitale, A R; Leocata, P; Lombardi, D; Lorenzo, C; D'Angelo, B; Macchiarelli, G; Cimini, A; Cifone, M G; Giuliani, M

2011-01-01

In the present work the effects of a new low frequency, high intensity ultrasound technology on human adipose tissue ex vivo were studied. In particular, we investigated the effects of both external and surgical ultrasound-irradiation (10 min) by evaluating, other than sample weight loss and fat release, also histological architecture alteration as well apoptosis induction. The influence of saline buffer tissue-infiltration on the effects of ultrasound irradiation was also examined. The results suggest that, in our experimental conditions, both transcutaneous and surgical ultrasound exposure caused a significant weight loss and fat release. This effect was more relevant when the ultrasound intensity was set at 100 % (~2.5 W/cm², for external device; ~19-21 W/cm2, for surgical device) compared to 70 % (~1.8 W/cm² for external device; ~13-14 W/cm2 for surgical device). Of note, the effectiveness of ultrasound was much higher when the tissue samples were previously infiltrated with saline buffer, in accordance with the knowledge that ultrasonic waves in aqueous solution better propagate with a consequently more efficient cavitation process. Moreover, the overall effects of ultrasound irradiation did not appear immediately after treatment but persisted over time, being significantly more relevant at 18 h from the end of ultrasound irradiation. Evaluation of histological characteristics of ultrasound-irradiated samples showed a clear alteration of adipose tissue architecture as well a prominent destruction of collagen fibers which were dependent on ultrasound intensity and most relevant in saline buffer-infiltrated samples. The structural changes of collagen bundles present between the lobules of fat cells were confirmed through scanning electron microscopy (SEM) which clearly demonstrated how ultrasound exposure induced a drastic reduction in the compactness of the adipose connective tissue and an irregular arrangement of the fibers with a consequent alteration in the spatial architecture. The analysis of the composition of lipids in the fat released from adipose tissue after ultrasound treatment with surgical device showed, in agreement with the level of adipocyte damage, a significant increase mainly of triglycerides and cholesterol. Finally, ultrasound exposure had been shown to induce apoptosis as shown by the appearance DNA fragmentation. Accordingly, ultrasound treatment led to down-modulation of procaspase-9 expression and an increased level of caspase-3 active form.

Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

PubMed

Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

2017-05-01

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Lymphocytes and macrophages in adipose tissue in obesity: markers or makers of subclinical inflammation?

PubMed

Cinkajzlová, Anna; Mráz, Miloš; Haluzík, Martin

2017-05-01

Obesity is accompanied by the development of chronic low-grade inflammation in adipose tissue. The presence of chronic inflammatory response along with metabolically harmful factors released by adipose tissue into the circulation is associated with several metabolic complications of obesity such as type 2 diabetes mellitus or accelerated atherosclerosis. The present review is focused on macrophages and lymphocytes and their possible role in low-grade inflammation in fat. Both macrophages and lymphocytes respond to obesity-induced adipocyte hypertrophy by their migration into adipose tissue. After activation and differentiation, they contribute to the development of local inflammatory response and modulation of endocrine function of adipose tissue. Despite intensive research, the exact role of lymphocytes and macrophages within adipose tissue is only partially clarified and various data obtained by different approaches bring ambiguous information with respect to their polarization and cytokine production. Compared to immunocompetent cells, the role of adipocytes in the obesity-related adipose tissue inflammation is often underestimated despite their abundant production of factors with immunomodulatory actions such as cytokines or adipokines such as leptin, adiponektin, and others. In summary, conflicting evidence together with only partial correlation of in vitro findings with true in vivo situation due to great heterogeneity and molecular complexity of tissue environment calls for intensive research in this rapidly evolving and important area.

An adipose segmentation and quantification scheme for the intra abdominal region on minipigs

NASA Astrophysics Data System (ADS)

Engholm, Rasmus; Dubinskiy, Aleksandr; Larsen, Rasmus; Hanson, Lars G.; Christoffersen, Berit Østergaard

2006-03-01

This article describes a method for automatic segmentation of the abdomen into three anatomical regions: subcutaneous, retroperitoneal and visceral. For the last two regions the amount of adipose tissue (fat) is quantified. According to recent medical research, the distinction between retroperitoneal and visceral fat is important for studying metabolic syndrome, which is closely related to diabetes. However previous work has neglected to address this point, treating the two types of fat together. We use T1-weighted three-dimensional magnetic resonance data of the abdomen of obese minipigs. The pigs were manually dissected right after the scan, to produce the "ground truth" segmentation. We perform automatic segmentation on a representative slice, which on humans has been shown to correlate with the amount of adipose tissue in the abdomen. The process of automatic fat estimation consists of three steps. First, the subcutaneous fat is removed with a modified active contour approach. The energy formulation of the active contour exploits the homogeneous nature of the subcutaneous fat and the smoothness of the boundary. Subsequently the retroperitoneal fat located around the abdominal cavity is separated from the visceral fat. For this, we formulate a cost function on a contour, based on intensities, edges, distance to center and smoothness, so as to exploit the properties of the retroperitoneal fat. We then globally optimize this function using dynamic programming. Finally, the fat content of the retroperitoneal and visceral regions is quantified based on a fuzzy c-means clustering of the intensities within the segmented regions. The segmentation proved satisfactory by visual inspection, and closely correlated with the manual dissection data. The correlation was 0.89 for the retroperitoneal fat, and 0.74 for the visceral fat.

Antiobesity effects of resveratrol: which tissues are involved?

PubMed

Fernández-Quintela, Alfredo; Milton-Laskibar, Iñaki; González, Marcela; Portillo, Maria P

2017-09-01

The prevalence of obesity has been increasing in recent decades and is reaching epidemic proportions. The current options for overweight and obesity management are energy restriction and physical activity. However, compliance with these treatments is frequently poor and less successful than expected. Therefore, the scientific community is interested in active biomolecules, which may be useful in body weight management. Among them, resveratrol (3,5,4'-trihydroxy-trans-stilbene) has generated great interest as an antiobesity agent. The focus of this report is the mechanisms of action of resveratrol on several tissues (i.e., white and brown adipose tissues, liver, and skeletal muscle). Resveratrol blunts fat accumulation through decreasing adipogenesis and/or de novo lipogenesis in white adipose tissue. The effects on lipolysis are controversial. Regarding brown adipose tissue, resveratrol increases the capacity for adaptive thermogenesis. As far as liver and skeletal muscle is concerned, resveratrol increases lipid oxidation in both tissues. Therefore, in rodents, there is a general consensus concerning the effect of resveratrol on reducing body fat accumulation. By contrast, in humans, the studies are scarce, and no clear antiobesity action has been revealed so far. © 2017 New York Academy of Sciences.

Liposuction: more curettage than aspiration.

PubMed

Mottura, A A

1991-01-01

After infiltration with epinephrine solution in each adipose area, an 8- or 10-mm cannula, without the suction tube connected, was introduced. With a curettage maneuver and by directing the cannula upward, the fat began to come out spontaneously. After obtaining a considerable amount of fat, the suction tube was connected and the remaining fat tissue aspirated at low suction power (250 mm Hg). With this curettage maneuver adiposity of the abdomen, knees, and trochanteric areas can be reduced. However, in the back, buttocks, or thighs, where adiposity is more fibrous, aspiration is needed from the start in almost every case, but always at low-power suction. This procedure is indicated in particular for the face and neck and for secondary liposuction. The fact that fat comes out easily through the cannula (without suction) demonstrates that the curettage maneuver is more important than the aspiration. Only with curettage can a considerable amount of fat be removed. No fat is removed when aspiration of 1 atm without a curettage maneuver is used. Suction only helps to remove fat already mobilized and free in the cannula. Our experience includes 34 patients.

Influence of upper and lower body adipose tissue on insulin sensitivity in South Asian men.

PubMed

Balakrishnan, Preetha; Grundy, Scott M; Islam, Arsalla; Dunn, Fredrick; Vega, Gloria Lena

2012-10-01

South Asians have a high prevalence of insulin resistance, which predisposes to type 2 diabetes. In the current study, we examined whether insulin sensitivity in South Asian men and men of European descent (Europids) relates to truncal and lower body fat, number of adipocytes, and cell size distribution. Fifteen South Asian men and 15 Europid young men with comparable body mass indexes completed assessments of insulin sensitivity, body composition analysis by dual-energy x-ray absorptiometry, and measurement of adipocyte cellularity in the subcutaneous abdominal (truncal) and gluteal (lower body) adipose tissue. The South Asians and the Europids had similar total body fat and fat contents in truncal and lower body regions. Compared to the Europids, the South Asians had a greater insulin resistance shown by fasting insulin, area-under-the-curve for postprandial insulin, oral glucose insulin sensitivity, homeostatic model assessment of insulin resistance, β-cell index, and triglyceride-to-high-density lipoprotein ratio. The South Asians had similar number of adipocytes to the Europids, but the South Asians had significantly higher ratios of small-to-larger adipocytes. The South Asians further had a higher fraction of very large adipocytes. In both South Asians and Europids, truncal fat was positively associated with insulin resistance. In the South Asians but not in the Europids, lower body fat was associated with severity of insulin resistance. The results suggest first, a higher ratio of small-to-larger adipocytes in the South Asians consistent with a lesser lipid storage capacity of adipose tissue; and second, the positive association of lower body fat with insulin resistance in the South Asians implies that fat in their lower body worsens insulin resistance. This association was not observed in the Europids.

Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue

PubMed Central

Landrier, Jean-Francois; Kasiri, Elnaz; Karkeni, Esma; Mihály, Johanna; Béke, Gabriella; Weiss, Kathrin; Lucas, Renata; Aydemir, Gamze; Salles, Jérome; Walrand, Stéphane; de Lera, Angel R.; Rühl, Ralph

2017-01-01

Adiponectin is an adipocyte-derived adipokine with potent antidiabetic, anti-inflammatory, and antiatherogenic activity. Long-term, high-fat diet results in gain of body weight, adiposity, further inflammatory-based cardiovascular diseases, and reduced adiponectin secretion. Vitamin A derivatives/retinoids are involved in several of these processes, which mainly take place in white adipose tissue (WAT). In this study, we examined adiponectin expression as a function of dietary high-fat and high–vitamin A conditions in mice. A decrease of adiponectin expression in addition to an up-regulation of aldehyde dehydrogenase A1 (ALDH1A1), retinoid signaling, and retinoic acid response element signaling was selectively observed in WAT of mice fed a normal–vitamin A, high-fat diet. Reduced adiponectin expression in WAT was also observed in mice fed a high–vitamin A diet. Adipocyte cell culture revealed that endogenous and synthetic retinoic acid receptor (RAR)α- and RARγ-selective agonists, as well as a synthetic retinoid X receptor agonist, efficiently reduced adiponectin expression, whereas ALDH1A1 expression only increased with RAR agonists. We conclude that reduced adiponectin expression under high-fat dietary conditions is dependent on 1) increased ALDH1A1 expression in adipocytes, which does not increase all-trans-retinoic acid levels; 2) further RAR ligand–induced, WAT-selective, increased retinoic acid response element–mediated signaling; and 3) RAR ligand–dependent reduction of adiponectin expression.—Landrier, J.-F., Kasiri, E., Karkeni, E., Mihály, J., Béke, G., Weiss, K., Lucas, R., Aydemir, G., Salles, J., Walrand, S., de Lera, A. R., Rühl, R. Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue. PMID:27729412

Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial.

PubMed

Zelicha, Hila; Schwarzfuchs, Dan; Shelef, Ilan; Gepner, Yftach; Tsaban, Gal; Tene, Lilac; Yaskolka Meir, Anat; Bilitzky, Avital; Komy, Oded; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusi, Benjamin; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Haviv, Yosef S; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2018-08-01

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m 2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. NCT01530724. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis

PubMed Central

Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

2015-01-01

It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors. PMID:26599360

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

Perilipin-2 Deletion Promotes Carbohydrate-Mediated Browning of White Adipose Tissue at Ambient Temperature.

PubMed

Libby, Andrew E; Bales, Elise S; Monks, Jenifer; Orlicky, David J; McManaman, James L

2018-06-04

Mice lacking Perilipin-2 (Plin2-null) are resistant to obesity, insulin resistance, and fatty liver induced by western or high fat diets. In the current study, we found that compared to wild type (WT) mice on western diet, Plin2-null adipose tissue was more insulin sensitive, and that inguinal subcutaneous white adipose tissue (iWAT) exhibited profound browning and robust induction of thermogenic and carbohydrate responsive genetic programs at room temperature. Surprisingly, these Plin2-null responses correlated with the content of simple carbohydrates, rather than fat, in the diet, and were independent of adipose Plin2 expression. To define Plin2 and sugar effects on adipose browning, WT and Plin2-null mice were placed on chow diets containing 20% sucrose in their drinking water for 6 weeks. Compared to WT mice, iWAT of Plin2-null mice exhibited pronounced browning and striking increases in the expression of thermogenic and insulin responsive genes on this diet. Significantly, Plin2-null iWAT browning was associated with reduced sucrose intake and elevated serum FGF21 levels, which correlated with greatly enhanced hepatic FGF21 production. These data identify Plin2 actions as novel mediators of sugar-induced adipose browning through indirect effects of hepatic FGF21 expression, and suggest that adipose browning mechanisms may contribute to Plin2-null resistance to obesity. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Quantification of Absolute Fat Mass by Magnetic Resonance Imaging: a Validation Study against Chemical Analysis

PubMed Central

Hu, Houchun H.; Li, Yan; Nagy, Tim R.; Goran, Michael I.; Nayak, Krishna S.

2011-01-01

Objective To develop a magnetic resonance imaging (MRI)-based approach for quantifying absolute fat mass in organs, muscles, and adipose tissues, and to validate its accuracy against reference chemical analysis (CA). Methods Chemical-shift imaging can accurately decompose water and fat signals from the acquired MRI data. A proton density fat fraction (PDFF) can be computed from the separated images, and reflects the relative fat content on a voxel-by-voxel basis. The PDFF is mathematically closely related to the fat mass fraction and can be converted to absolute fat mass in grams by multiplying by the voxel volume and the mass density of fat. In this validation study, 97 freshly excised and unique samples from four pigs, comprising of organs, muscles, and adipose and lean tissues were imaged by MRI and then analyzed independently by CA. Linear regression was used to assess correlation, agreement, and measurement differences between MRI and CA. Results Considering all 97 samples, a strong correlation and agreement was obtained between MRI and CA-derived fat mass (slope = 1.01, intercept = 1.99g, r2 = 0.98, p < 0.01). The mean difference d between MRI and CA was 2.17±3.40g. MRI did not exhibit any tendency to under or overestimate CA (p > 0.05). When considering samples from each pig separately, the results were (slope = 1.05, intercept = 1.11g, r2 = 0.98, d = 2.66±4.36g), (slope = 0.99, intercept = 2.33g, r2 = 0.99, d = 1.88±2.68g), (slope = 1.07, intercept = 1.52g, r2 = 0.96, d = 2.73±2.50g), and (slope=0.92, intercept=2.84g, r2 = 0.97, d = 1.18±3.90g), respectively. Conclusion Chemical-shift MRI and PDFF provides an accurate means of determining absolute fat mass in organs, muscles, and adipose and lean tissues. PMID:23204926

Impact of pioglitazone and bradykinin type 1 receptor antagonist on type 2 diabetes in high-fat diet-fed C57BL/6J mice.

PubMed

El Akoum, S; Haddad, Y; Couture, R

2017-09-01

Type 2 diabetes (T2D) is a major complication of obesity and a leading cause of morbidity and mortality. Antagonizing bradykinin type 1 receptor (B1R) improved body and tissue fat mass and reversed vascular and adipose tissue inflammation in a rat model of insulin resistance. This study aimed at evaluating further the role of B1R in a mouse model of T2D by comparing the antidiabetic and anti-inflammatory effects of the B1R antagonist SSR240612 (SSR) in adipose tissue with those of pioglitazone (TZD), an activator of peroxisome proliferator-activated receptor gamma. C57BL/6J mice were fed with high-fat diet (HFD) or standard diet (control) for 20 weeks. Yet, during the last 4 weeks, HFD-fed mice were administered SSR and TZD (10 mg kg -1  d -1 each) as monotherapy or combined therapy subcutaneously. The impact of treatments was measured on metabolic hormones levels (ELISA), adipose tissue inflammatory status and the expression of candidate genes involved in T2D (quantitative real-time polymerase chain reaction and western blot). SSR240612 and TZD treatments improved hyperglycaemia, hyperinsulinaemia, insulin resistance, adipose tissue inflammation (expression of B1R, chemokine ligand 2, F4/80 and tumour necrosis factor) and modulated adipogenesis (peroxisome proliferator-activated receptor gamma, adipocytes' protein 2 and CD40 expressions) in HFD-fed mice. Yet, SSR was more effective than TZD to reduce visceral fat mass and resistin. TZD/SSR combined treatment had an additive effect to improve insulin sensitivity and glucose intolerance. Bradykinin type 1 receptor antagonism could represent a promising therapeutic tool in combination with TZD for the treatment of T2D, obesity and insulin resistance.

Large Yellow Tea Attenuates Macrophage-Related Chronic Inflammation and Metabolic Syndrome in High-Fat Diet Treated Mice.

PubMed

Xu, Na; Chu, Jun; Wang, Min; Chen, Ling; Zhang, Liang; Xie, Zhongwen; Zhang, Jinsong; Ho, Chi-Tang; Li, Daxiang; Wan, Xiaochun

2018-04-18

Large yellow tea is a traditional beverage in China with a unique toasty flavor. A preliminary study using 3T3-L1 cells indicated that large yellow tea possessed more potent lipid-lowering efficacy than green, black, dark, and white teas. In the present study we further investigated its influence on metabolic syndrome in a high-fat diet (HFD) mouse model with an emphasis on dose response. Thirty-two C57BL/6 male mice were randomly divided into 4 groups: low-fat diet (LFD), HFD, HFD + 2.5% large yellow tea hot-water extract (YT, equivalent to 10 cups of tea daily for humans), HFD + 0.5% YT. Our data indicated that YT treatment for 12 weeks significantly reduced body weight, liver weight, and adipose tissue weight of the mice; lowered serum insulin and leptin; and raised serum adiponectin with dose effect. H&E staining showed that the HFD group exhibited significant enlargement of adipose cell sizes and the corresponding decrease of adipose cell numbers, which were dose-dependently attenuated in both YT groups. IHC results revealed that YT decreased macrophage recruitment in the liver, epididymal adipose tissue, and subcutaneous adipose tissue and depressed serum inflammatory cytokines including TNF-α, MCP-1, IFN-γ, IL-6, and IL-1β, in a dose-dependent manner. In addition, YT decreased serum glucose, TC, TG, LDL-C, and HDL-C, as well as ameliorated glucose intolerance and insulin resistance independent of dose. Overall, YT would be a unique tea with dose-independent antihyperglycemic and robust lipid-lowering efficacies.

MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease.

PubMed

Schiffer, Lina; Kempegowda, Punith; Arlt, Wiebke; O'Reilly, Michael W

2017-09-01

Female androgen excess and male androgen deficiency manifest with an overlapping adverse metabolic phenotype, including abdominal obesity, insulin resistance, type 2 diabetes mellitus, non-alcoholic fatty liver disease and an increased risk of cardiovascular disease. Here, we review the impact of androgens on metabolic target tissues in an attempt to unravel the complex mechanistic links with metabolic dysfunction; we also evaluate clinical studies examining the associations between metabolic disease and disorders of androgen metabolism in men and women. We conceptualise that an equilibrium between androgen effects on adipose tissue and skeletal muscle underpins the metabolic phenotype observed in female androgen excess and male androgen deficiency. Androgens induce adipose tissue dysfunction, with effects on lipid metabolism, insulin resistance and fat mass expansion, while anabolic effects on skeletal muscle may confer metabolic benefits. We hypothesise that serum androgen concentrations observed in female androgen excess and male hypogonadism are metabolically disadvantageous, promoting adipose and liver lipid accumulation, central fat mass expansion and insulin resistance. © 2017 The authors.

MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease

PubMed Central

Schiffer, Lina; Kempegowda, Punith; Arlt, Wiebke

2017-01-01

Female androgen excess and male androgen deficiency manifest with an overlapping adverse metabolic phenotype, including abdominal obesity, insulin resistance, type 2 diabetes mellitus, non-alcoholic fatty liver disease and an increased risk of cardiovascular disease. Here, we review the impact of androgens on metabolic target tissues in an attempt to unravel the complex mechanistic links with metabolic dysfunction; we also evaluate clinical studies examining the associations between metabolic disease and disorders of androgen metabolism in men and women. We conceptualise that an equilibrium between androgen effects on adipose tissue and skeletal muscle underpins the metabolic phenotype observed in female androgen excess and male androgen deficiency. Androgens induce adipose tissue dysfunction, with effects on lipid metabolism, insulin resistance and fat mass expansion, while anabolic effects on skeletal muscle may confer metabolic benefits. We hypothesise that serum androgen concentrations observed in female androgen excess and male hypogonadism are metabolically disadvantageous, promoting adipose and liver lipid accumulation, central fat mass expansion and insulin resistance. PMID:28566439

Fasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16

PubMed Central

Ding, Hanying; Zheng, Shasha; Garcia-Ruiz, Daniel; Hou, Dongxia; Wei, Zhe; Liao, Zhicong; Li, Limin; Zhang, Yujing; Han, Xiao; Zen, Ke; Zhang, Chen-Yu; Li, Jing; Jiang, Xiaohong

2016-01-01

Visceral adiposity is strongly associated with metabolic disease risk, whereas subcutaneous adiposity is comparatively benign. However, their relative physiological importance in energy homeostasis remains unclear. Here, we show that after 24-h fasting, the subcutaneous adipose tissue of mice acquires key properties of visceral fat. During this fast-induced ‘visceralization', upregulation of miR-149-3p directly targets PR domain containing 16 (PRDM16), a key coregulatory protein required for the ‘browning' of white fat. In cultured inguinal preadipocytes, overexpression of miR-149-3p promotes a visceral-like switch during cell differentiation. Mice deficient in miR-149-3p display an increase in whole-body energy expenditure, with enhanced thermogenesis of inguinal fat. However, a visceral-like adipose phenotype is observed in inguinal depots overexpressing miR-149-3p. These results indicate that in addition to the capacity of ‘browning' to defend against hypothermia during cold exposure, the subcutaneous adipose depot is also capable of ‘whitening' to preserve energy during fasting, presumably to maintain energy balance, via miR-149-3p-mediated regulation of PRDM16. PMID:27240637

Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages

PubMed Central

Tarabra, Elena; An Lee, Ting-Wen; Zammit, Victor A.; Vatish, Manu; Yamada, Eijiro; Pessin, Jeffrey E.; Bastie, Claire C.

2017-01-01

Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency (fynKO) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats. PMID:29156823

Depot-Specific Response of Adipose Tissue to Diet-Induced Inflammation: The Retinoid-Related Orphan Receptor α (RORα) Involved?

PubMed

Kadiri, Sarah; Auclair, Martine; Capeau, Jacqueline; Antoine, Bénédicte

2017-11-01

Epididymal adipose tissue (EAT), a visceral fat depot, is more closely associated with metabolic dysfunction than inguinal adipose tissue (IAT), a subcutaneous depot. This study evaluated whether the nuclear receptor RORα, which controls inflammatory processes, could be implicated. EAT and IAT were compared in a RORα loss-of-function mouse (sg/sg) and in wild-type (WT) littermates, fed a standard diet (SD) or a Western diet (WD), to evaluate the impact of RORα expression on inflammatory status and on insulin sensitivity (IS) of each fat depot according to the diet. Sg/sg mice fed the SD exhibited a decreased inflammatory status and a higher IS in their fat depots than WT mice. WD-induced obesity had distinct effects on the two fat depots. In WT mice, EAT exhibited increased inflammation and insulin resistance while IAT showed reduced inflammation and improved IS, together with a depot-specific increase of RORα, and its target gene IκBα, in the stroma vascular fraction (SVF). Conversely, in sg/sg mice, WD increased inflammation and lowered IS of IAT but not of EAT. These findings suggest an anti-inflammatory role for RORα in response to WD, which occurs at the level of SVF of IAT, thus possibly contributing to the "healthy" expansion of IAT. © 2017 The Obesity Society.

Fate of higher brominated PBDEs in lactating cows.

PubMed

Kierkegaard, Amelie; Asplund, Lillemor; de Wit, Cynthia A; McLachlan, Michael S; Thomas, Gareth O; Sweetman, Andrew J; Jones, Kevin C

2007-01-15

Dietary intake studies of lower brominated diphenyl ethers (BDEs) have shown that fish and animal products are important vectors of human exposure, but almost no data exist for higher brominated BDEs. Therefore, the fate of hepta- to decaBDEs was studied in lactating cows exposed to a naturally contaminated diet by analyzing feed, feces, and milk samples from a previous mass balance study of PCB. Tissue distribution was studied in one cow slaughtered after the experiment. BDE-209 was the dominant congener in feed, organs, adipose tissues, and feces, but not in milk. In contrast to PCBs and lower brominated BDEs, concentrations of hepta- to decaBDEs in adipose tissue were 9-80 times higher than in milk fat and the difference increased with degree of bromination/log K(OW). The congener profiles in adipose tissue and feed differed; BDE-207, BDE-196, BDE-197, and BDE-182 accumulated to a surprisingly greater extent in the fat compared to their isomers, suggesting metabolic debromination of BDE-209 to these BDEs. The results indicate that meat rather than dairy product consumption may be an important human exposure route to higher brominated BDEs.

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

PubMed Central

Yamaguchi, Yukiko; Cavallero, Susana; Patterson, Michaela; Shen, Hua; Xu, Jian; Kumar, S. Ram; Sucov, Henry M.

2015-01-01

The hearts of many mammalian species are surrounded by an extensive layer of fat called epicardial adipose tissue (EAT). The lineage origins and determinative mechanisms of EAT development are unclear, in part because mice and other experimentally tractable model organisms are thought to not have this tissue. In this study, we show that mouse hearts have EAT, localized to a specific region in the atrial–ventricular groove. Lineage analysis indicates that this adipose tissue originates from the epicardium, a multipotent epithelium that until now is only established to normally generate cardiac fibroblasts and coronary smooth muscle cells. We show that adoption of the adipocyte fate in vivo requires activation of the peroxisome proliferator activated receptor gamma (PPARγ) pathway, and that this fate can be ectopically induced in mouse ventricular epicardium, either in embryonic or adult stages, by expression and activation of PPARγ at times of epicardium–mesenchymal transformation. Human embryonic ventricular epicardial cells natively express PPARγ, which explains the abundant presence of fat seen in human hearts at birth and throughout life. PMID:25646471

The initial changes of fat deposits during the decomposition of human and pig remains.

PubMed

Notter, Stephanie J; Stuart, Barbara H; Rowe, Rebecca; Langlois, Neil

2009-01-01

The early stages of adipocere formation in both pig and human adipose tissue in aqueous environments have been investigated. The aims were to determine the short-term changes occurring to fat deposits during decomposition and to ascertain the suitability of pigs as models for human decomposition. Subcutaneous adipose tissue from both species after immersion in distilled water for up to six months was compared using Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry. Changes associated with decomposition were observed, but no adipocere was formed during the initial month of decomposition for either tissue type. Early-stage adipocere formation in pig samples during later months was detected. The variable time courses for adipose tissue decomposition were attributed to differences in the distribution of total fatty acids between species. Variations in the amount of sodium, potassium, calcium, and magnesium were also detected between species. The study shows that differences in total fatty acid composition between species need to be considered when interpreting results from experimental decomposition studies using pigs as human body analogs.

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.

Arboreal adaptations of body fat in wild toque macaques (Macaca sinica) and the evolution of adiposity in primates.

PubMed

Dittus, Wolfgang P J

2013-11-01

There is a paucity of information on body composition and fat patterning in wild nonhuman primates. Dissected adipose tissue from wild toque macaques (Macaca sinica) (WTM), feeding on a natural diet, accounted for 2.1% of body weight. This was far less than fatness reported for nonhuman primates raised in captivity or for contemporary humans. In WTM, fatness increased with age and diet richness, but did not differ by sex. In WTM (none of which were obese) intra-abdominal fat filled first, and "excess" fat was stored peripherally in a ratio of about 6:1. Intermuscular fat was minimal (0.1%). The superficial paunch held <15% of subcutaneous fat weight in contrast to its much larger proportions in obese humans and captive monkeys where most added fat accumulates subcutaneously. With increasing total adiposity, accumulating fat shifted in its distribution among eight different main internal and peripheral deposit areas-consistent with maintaining body balance and a low center of gravity. The available data suggest that, in arboreal primates, adaptations for agile locomotion and terminal branch feeding set constraints on the quantity and distribution of fat. The absence of a higher percentage of body fat in females and neonates (as are typical of humans) suggests that arboreal adaptations preclude the development of fat-dependent, large-brained infants and the adipose-rich mothers needed to sustain them. The lifestyle and body composition of wild primates represent a more appropriate model for early human foragers than well-fed captive monkeys do. Copyright © 2013 Wiley Periodicals, Inc.

Breast tissue engineering.

PubMed

Patrick, Charles W

2004-01-01

Tissue engineering has the potential to redefine rehabilitation for the breast cancer patient by providing a translatable strategy that restores the postmastectomy breast mound while concomitantly obviating limitations realized with contemporary reconstructive surgery procedures. The engineering design goal is to provide a sufficient volume of viable fat tissue based on a patient's own cells such that deficits in breast volume can be abrogated. To be sure, adipose tissue engineering is in its infancy, but tremendous strides have been made. Numerous studies attest to the feasibility of adipose tissue engineering. The field is now poised to challenge barriers to clinical translation that are germane to most tissue engineering applications, namely scale-up, large animal model development, and vascularization. The innovative and rapid progress of adipose engineering to date, as well as opportunities for its future growth, is presented.

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

The ubiquitin ligase Siah2 regulates obesity-induced adipose tissue inflammation.

PubMed

Kilroy, Gail; Carter, Lauren E; Newman, Susan; Burk, David H; Manuel, Justin; Möller, Andreas; Bowtell, David D; Mynatt, Randall L; Ghosh, Sujoy; Floyd, Z Elizabeth

2015-11-01

Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases regulate inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. Herein, the effect of the ubiquitin ligase Siah2 on obesity-related adipose tissue inflammation was examined. Wild-type and Siah2KO mice were fed a low- or high-fat diet for 16 weeks. Indirect calorimetry, body composition, and glucose and insulin tolerance were assayed along with glucose and insulin levels. Gene and protein expression, immunohistochemistry, adipocyte size distribution, and lipolysis were also analyzed. Enlarged adipocytes in obese Siah2KO mice were not associated with obesity-induced insulin resistance. Proinflammatory gene expression, stress kinase signaling, fibrosis, and crown-like structures were reduced in the Siah2KO adipose tissue, and Siah2KO adipocytes were more responsive to insulin-dependent inhibition of lipolysis. Loss of Siah2 increased expression of PPARγ target genes involved in lipid metabolism and decreased expression of proinflammatory adipokines regulated by PPARγ. Siah2 links adipocyte hypertrophy with adipocyte dysfunction and recruitment of proinflammatory immune cells to adipose tissue. Selective regulation of PPARγ activity is a Siah2-mediated mechanism contributing to obesity-induced adipose tissue inflammation. © 2015 The Obesity Society.

Optical body fat measurement might contribute to the search for a predictor of type-2 diabetes mellitus

NASA Astrophysics Data System (ADS)

Tafeit, Erwin; Horejsi, Renate; Sudi, Karl; Berg, Aloys; Reibnegger, Gilbert; Moeller, Reinhard

2001-10-01

The optical device LIPOMETER allows for non-invasive, quick, precise and safe determination of subcutaneous fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). Previously we showed how the high-dimensional SAT-Top information of women with type-2 diabetes mellitus (NIDDM) and a health control group can be analysed and represented in low-dimensional plots by applying special artificial neural networks (ANNs). Three top-down sorted subcutaneous adipose tissue compartments were determined (upper trunk, lower trunk, legs). NIDDM women provided significantly higher upper trunk obesity and significantly lower leg obesity (apple type), as compared with their healthy control group. Now we apply those ANN results on SAT-Top measurements of young and healthy women, comparing their individual subcutaneous fat pattern to the body fat distribution of NIDDM women and to the normal fat development of healthy women. Some of these young and healthy women provide a subcutaneous fat distribution very similar to the SAT-Top results of NIDDM women, which might increase their risk for this disease later in life.

Reproducible MRI Measurement of Adipose Tissue Volumes in Genetic and Dietary Rodent Obesity Models

PubMed Central

Johnson, David H.; Flask, Chris A.; Ernsberger, Paul R.; Wong, Wilbur C. K.; Wilson, David L.

2010-01-01

Purpose To develop ratio MRI [lipid/(lipid+water)] methods for assessing lipid depots and compare measurement variability to biological differences in lean controls (spontaneously hypertensive rats, SHRs), dietary obese (SHR-DO), and genetic/dietary obese (SHROBs) animals. Materials and Methods Images with and without CHESS water-suppression were processed using a semi-automatic method accounting for relaxometry, chemical shift, receive coil sensitivity, and partial volume. Results Partial volume correction improved results by 10–15%. Over six operators, volume variation was reduced to 1.9 ml from 30.6 ml for single-image-analysis with intensity inhomogeneity. For three acquisitions on the same animal, volume reproducibility was <1%. SHROBs had 6X visceral and 8X subcutaneous adipose tissue than SHRs. SHR-DOs had enlarged visceral depots (3X SHRs). SHROB had significantly more subcutaneous adipose tissue, indicating a strong genetic component to this fat depot. Liver ratios in SHR-DO and SHROB were higher than SHR, indicating elevated fat content. Among SHROBs, evidence suggested a phenotype SHROB* having elevated liver ratios and visceral adipose tissue volumes. Conclusion Effects of diet and genetics on obesity were significantly larger than variations due to image acquisition and analysis, indicating that these methods can be used to assess accumulation/depletion of lipid depots in animal models of obesity. PMID:18821617

ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity.

PubMed

de Haan, Willeke; Bhattacharjee, Alpana; Ruddle, Piers; Kang, Martin H; Hayden, Michael R

2014-03-01

Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1(-ad/-ad)). When fed a high-fat, high-cholesterol diet, ABCA1(-ad/-ad) mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1(-ad/-ad) mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis.

FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

PubMed

Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

2018-06-01

Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing inflammation and insulin resistance in obesity and diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

Obesity, regional body fat distribution, and the metabolic syndrome in older men and women.

PubMed

Goodpaster, Bret H; Krishnaswami, Shanthi; Harris, Tamara B; Katsiaras, Andreas; Kritchevsky, Steven B; Simonsick, Eleanor M; Nevitt, Michael; Holvoet, Paul; Newman, Anne B

2005-04-11

The metabolic syndrome is a disorder that includes dyslipidemia, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cardiovascular disease. We determined whether patterns of regional fat deposition are associated with metabolic syndrome in older adults. A cross-sectional study was performed that included a random, population-based, volunteer sample of Medicare-eligible adults within the general communities of Pittsburgh, Pa, and Memphis, Tenn. The subjects consisted of 3035 men and women aged 70 to 79 years, of whom 41.7% were black. Metabolic syndrome was defined by Adult Treatment Panel III criteria, including serum triglyceride level, high-density lipoprotein cholesterol level, glucose level, blood pressure, and waist circumference. Visceral, subcutaneous abdominal, intermuscular, and subcutaneous thigh adipose tissue was measured by computed tomography. Visceral adipose tissue was associated with the metabolic syndrome in men who were of normal weight (odds ratio, 95% confidence interval: 2.1, 1.6-2.9), overweight (1.8, 1.5-2.1), and obese (1.2, 1.0-1.5), and in women who were of normal weight (3.3, 2.4-4.6), overweight (2.4, 2.0-3.0), and obese (1.7, 1.4-2.1), adjusting for race. Subcutaneous abdominal adipose tissue was associated with the metabolic syndrome only in normal-weight men (1.3, 1.1-1.7). Intermuscular adipose tissue was associated with the metabolic syndrome in normal-weight (2.3, 1.6-3.5) and overweight (1.2, 1.1-1.4) men. In contrast, subcutaneous thigh adipose tissue was inversely associated with the metabolic syndrome in obese men (0.9, 0.8-1.0) and women (0.9, 0.9-1.0). In addition to general obesity, the distribution of body fat is independently associated with the metabolic syndrome in older men and women, particularly among those of normal body weight.

The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women

PubMed Central

de Paula, Francisco J. A.; de Araújo, Iana M.; Carvalho, Adriana L.; Elias, Jorge; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.

2015-01-01

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism. PMID:26067489

The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women.

PubMed

de Paula, Francisco J A; de Araújo, Iana M; Carvalho, Adriana L; Elias, Jorge; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H

2015-01-01

Bone marrow harbors a significant amount of body adipose tissue (BMAT). While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism.

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Diagnostic utility of aP2/FABP4 expression in soft tissue tumours.

PubMed

Kashima, T G; Turley, H; Dongre, A; Pezzella, F; Athanasou, N A

2013-04-01

Adipocyte P2 (aP2), also known as fatty acid-binding protein 4 (FABP4), is a fatty acid-binding protein found in the cytoplasm of cells of adipocyte differentiation. In this study, we examined a large number of soft tissue tumours with a commercial polyclonal anti-aP2/FABP4 antibody and a newly developed mouse monoclonal antibody raised against this protein to determine the diagnostic utility of aP2/FABP4 as a marker of tumours of adipose differentiation. A mouse monoclonal antibody, clone 175d, was raised against a mixture of synthetic peptides corresponding to the amino acid sequence of residues 10-28 and 121-132 of the human aP2/FABP4 protein. Antigen expression with polyclonal and monoclonal antibodies was immunohistochemically determined in paraffin sections of normal adipose tissue and a wide range of benign and malignant primary soft tissue tumours (n = 200). aP2/FABP4 was expressed around the cytoplasmic lipid vacuole in white and brown fat cells in benign lipomas and hibernomas. Immature fat cells and lipoblasts in spindle cell/pleomorphic lipoma, atypical lipomatous tumour/well-differentiated liposarcoma, myxoid/round cell liposarcoma and pleomorphic liposarcoma also reacted strongly for aP2/FABP4. No specific staining was seen in non-adipose benign and malignant mesenchymal and non-mesenchymal tumours. aP2/FABP4 is expressed by mature and immature fat cells and is a marker of tumours of adipose differentiation. Immunophenotypic aP2/FABP4 expression is useful in identifying lipoblasts, and immunohistochemistry with polyclonal/monoclonal anti-aP2/FABP4 antibodies should be useful in distinguishing liposarcoma from other malignancies, particularly round cell, myxoid and pleomorphic soft tissue sarcomas.

Adipose and Muscle Tissue Gene Expression of Two Genes (NCAPG and LCORL) Located in a Chromosomal Region Associated with Cattle Feed Intake and Gain

PubMed Central

Lindholm-Perry, Amanda K.; Kuehn, Larry A.; Oliver, William T.; Sexten, Andrea K.; Miles, Jeremy R.; Rempel, Lea A.; Cushman, Robert A.; Freetly, Harvey C.

2013-01-01

A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG) and average daily feed intake (ADFI) in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only), cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01). These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues. PMID:24278337

A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue

PubMed Central

Fischer, I P; Irmler, M; Meyer, C W; Sachs, S J; Neff, F; Hrabě de Angelis, M; Beckers, J; Tschöp, M H; Hofmann, S M; Ussar, S

2018-01-01

Background/Objectives: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. Methods: In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. Results & Conclusions: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain. PMID:28901330

Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis.

PubMed

Lin, Heng-Hsu; Lee, Jen-Kuang; Yang, Chung-Yi; Lien, Yu-Chung; Huang, Jenq-Wen; Wu, Cho-Kai

2013-08-30

Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population. This was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p < 0.001) than controls. Visceral adipose tissue, hsCRP, and EpF all correlated significantly (p < 0.05) with LVDD. Multivariate regression analysis rendered the relationship between visceral adipose tissue and LVDD insignificant, whereas EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43-4.08, p < 0.01). EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e'; r = 0.27, p < 0.01). EpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis.

Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis

PubMed Central

2013-01-01

Background Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population. Methods This was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Results Subjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p < 0.001) than controls. Visceral adipose tissue, hsCRP, and EpF all correlated significantly (p < 0.05) with LVDD. Multivariate regression analysis rendered the relationship between visceral adipose tissue and LVDD insignificant, whereas EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43–4.08, p < 0.01). EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e’; r = 0.27, p < 0.01). Conclusion EpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis. PMID:24001037

High intensity interval training improves liver and adipose tissue insulin sensitivity.

PubMed

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

2015-12-01

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. 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. 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. 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.

EQUIFAT: A novel scoring system for the semi-quantitative evaluation of regional adipose tissues in Equidae.

PubMed

Morrison, Philippa K; Harris, Patricia A; Maltin, Charlotte A; Grove-White, Dai; Argo, Caroline McG

2017-01-01

Anatomically distinct adipose tissues represent variable risks to metabolic health in man and some other mammals. Quantitative-imaging of internal adipose depots is problematic in large animals and associations between regional adiposity and health are poorly understood. This study aimed to develop and test a semi-quantitative system (EQUIFAT) which could be applied to regional adipose tissues. Anatomically-defined, photographic images of adipose depots (omental, mesenteric, epicardial, rump) were collected from 38 animals immediately post-mortem. Images were ranked and depot-specific descriptors were developed (1 = no fat visible; 5 = excessive fat present). Nuchal-crest and ventro-abdominal-retroperitoneal adipose depot depths (cm) were transformed to categorical 5 point scores. The repeatability and reliability of EQUIFAT was independently tested by 24 observers. When half scores were permitted, inter-observer agreement was substantial (average κw: mesenteric, 0.79; omental, 0.79; rump 0.61) or moderate (average κw; epicardial, 0.60). Intra-observer repeatability was tested by 8 observers on 2 occasions. Kappa analysis indicated perfect (omental and mesenteric) and substantial agreement (epicardial and rump) between attempts. A further 207 animals were evaluated ante-mortem (age, height, breed-type, gender, body condition score [BCS]) and again immediately post-mortem (EQUIFAT scores, carcass weight). Multivariable, random effect linear regression models were fitted (breed as random effect; BCS as outcome variable). Only height, carcass weight, omental and retroperitoneal EQUIFAT scores remained as explanatory variables in the final model. The EQUIFAT scores developed here demonstrate clear functional differences between regional adipose depots and future studies could be directed towards describing associations between adiposity and disease risk in surgical and post-mortem situations.

EQUIFAT: A novel scoring system for the semi-quantitative evaluation of regional adipose tissues in Equidae

PubMed Central

Morrison, Philippa K.; Harris, Patricia A.; Maltin, Charlotte A.; Grove-White, Dai; Argo, Caroline McG.

2017-01-01

Anatomically distinct adipose tissues represent variable risks to metabolic health in man and some other mammals. Quantitative-imaging of internal adipose depots is problematic in large animals and associations between regional adiposity and health are poorly understood. This study aimed to develop and test a semi-quantitative system (EQUIFAT) which could be applied to regional adipose tissues. Anatomically-defined, photographic images of adipose depots (omental, mesenteric, epicardial, rump) were collected from 38 animals immediately post-mortem. Images were ranked and depot-specific descriptors were developed (1 = no fat visible; 5 = excessive fat present). Nuchal-crest and ventro-abdominal-retroperitoneal adipose depot depths (cm) were transformed to categorical 5 point scores. The repeatability and reliability of EQUIFAT was independently tested by 24 observers. When half scores were permitted, inter-observer agreement was substantial (average κw: mesenteric, 0.79; omental, 0.79; rump 0.61) or moderate (average κw; epicardial, 0.60). Intra-observer repeatability was tested by 8 observers on 2 occasions. Kappa analysis indicated perfect (omental and mesenteric) and substantial agreement (epicardial and rump) between attempts. A further 207 animals were evaluated ante-mortem (age, height, breed-type, gender, body condition score [BCS]) and again immediately post-mortem (EQUIFAT scores, carcass weight). Multivariable, random effect linear regression models were fitted (breed as random effect; BCS as outcome variable). Only height, carcass weight, omental and retroperitoneal EQUIFAT scores remained as explanatory variables in the final model. The EQUIFAT scores developed here demonstrate clear functional differences between regional adipose depots and future studies could be directed towards describing associations between adiposity and disease risk in surgical and post-mortem situations. PMID:28296956

Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging–measured adipose tissue depots in both HIV-infected and control subjects2

PubMed Central

Scherzer, Rebecca; Shen, Wei; Bacchetti, Peter; Kotler, Donald; Lewis, Cora E; Shlipak, Michael G; Heymsfield, Steven B

2008-01-01

Background Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects. Objective We compared anthropometric and magnetic resonance imaging (MRI)–based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects. Design The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors. Results In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r ≤ 0.07). Multivariate adjustment found no significant difference for optimally fitting models between the use of anthropometric and MRI measures, and the magnitudes of differences were small (adjusted R2 ≤ 0.06). For HOMA and HDL, WC appeared to be the best anthropometric correlate of metabolic complications, whereas, for triglycerides, the best was WHR. Conclusion Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects. PMID:18541572

Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging-measured adipose tissue depots in both HIV-infected and control subjects.

PubMed

Scherzer, Rebecca; Shen, Wei; Bacchetti, Peter; Kotler, Donald; Lewis, Cora E; Shlipak, Michael G; Heymsfield, Steven B; Grunfeld, Carl

2008-06-01

Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects. We compared anthropometric and magnetic resonance imaging (MRI)-based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects. The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors. In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r

Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

PubMed

Caetano, Luiz Carlos; Bonfleur, Maria Lúcia; Ribeiro, Rosane Aparecida; Nardelli, Tarlliza Romanna; Lubaczeuski, Camila; do Nascimento da Silva, Juliana; Carneiro, Everardo Magalhães; Balbo, Sandra Lucinei

2017-03-01

Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1β or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue.

PubMed

Lecoutre, Simon; Deracinois, Barbara; Laborie, Christine; Eberlé, Delphine; Guinez, Céline; Panchenko, Polina E; Lesage, Jean; Vieau, Didier; Junien, Claudine; Gabory, Anne; Breton, Christophe

2016-07-01

According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner. © 2016 Society for Endocrinology.

[Measurements of location of body fat distribution: an assessment of colinearity with body mass, adiposity and stature in female adolescents].

PubMed

Pereira, Patrícia Feliciano; Serrano, Hiara Miguel Stanciola; Carvalho, Gisele Queiroz; Ribeiro, Sônia Machado Rocha; Peluzio, Maria do Carmo Gouveia; Franceschini, Sylvia do Carmo Castro; Priore, Silvia Eloiza

2015-01-01

To verify the correlation between body fat location measurements with the body mass index (BMI), percentage of body fat (%BF) and stature, according to the nutritional status in female adolescents. A controlled cross sectional study was carried out with 113 adolescents (G1: 38 eutrophic, but with high body fat level, G2: 40 eutrophic and G3: 35 overweight) from public schools in Viçosa-MG, Brazil. The following measures have been assessed: weight, stature, waist circumference (WC), umbilical circumference (UC), hip circumference (HC), thigh circumference, waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), waist-to-thigh ratio (WTR), conicity index (CI), sagittal abdominal diameter (SAD), coronal diameter (CD), central skinfolds (CS) and peripheral (PS). The %BF was assessed by tetrapolar electric bioimpedance. The increase of central fat, represented by WC, UC, WSR, SAD, CD and CS, and the increase of peripheral fat indicated by HC and thigh were proportional to the increase of BMI and %BF. WC and especially the UC showed the strongest correlations with adiposity. Weak correlation between WHR, WTR, CI and CS/PS with adiposity were observed. The stature showed correlation with almost all the fat location measures, being regular or weak with waist. The results indicate colinearity between body mass and total adiposity with central and peripheral adipose tissue. We recommend the use of UC for assessing nutritional status of adolescents, because it showed the highest ability to predict adiposity in each group, and also presented regular or weak correlation with stature. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

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.

The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

PubMed

Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Kim, Ji-Eun; Kim, Seung-Chul; Jeung, Eui-Bae; Lee, Geun-Shik; Hwang, Dae-Youn; An, Beum-Soo

2015-07-01

Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantifying Abdominal Adipose Tissue and Thigh Muscle Volume and Hepatic Proton Density Fat Fraction: Repeatability and Accuracy of an MR Imaging-based, Semiautomated Analysis Method.

PubMed

Middleton, Michael S; Haufe, William; Hooker, Jonathan; Borga, Magnus; Dahlqvist Leinhard, Olof; Romu, Thobias; Tunón, Patrik; Hamilton, Gavin; Wolfson, Tanya; Gamst, Anthony; Loomba, Rohit; Sirlin, Claude B

2017-05-01

Purpose To determine the repeatability and accuracy of a commercially available magnetic resonance (MR) imaging-based, semiautomated method to quantify abdominal adipose tissue and thigh muscle volume and hepatic proton density fat fraction (PDFF). Materials and Methods This prospective study was institutional review board- approved and HIPAA compliant. All subjects provided written informed consent. Inclusion criteria were age of 18 years or older and willingness to participate. The exclusion criterion was contraindication to MR imaging. Three-dimensional T1-weighted dual-echo body-coil images were acquired three times. Source images were reconstructed to generate water and calibrated fat images. Abdominal adipose tissue and thigh muscle were segmented, and their volumes were estimated by using a semiautomated method and, as a reference standard, a manual method. Hepatic PDFF was estimated by using a confounder-corrected chemical shift-encoded MR imaging method with hybrid complex-magnitude reconstruction and, as a reference standard, MR spectroscopy. Tissue volume and hepatic PDFF intra- and interexamination repeatability were assessed by using intraclass correlation and coefficient of variation analysis. Tissue volume and hepatic PDFF accuracy were assessed by means of linear regression with the respective reference standards. Results Adipose and thigh muscle tissue volumes of 20 subjects (18 women; age range, 25-76 years; body mass index range, 19.3-43.9 kg/m 2 ) were estimated by using the semiautomated method. Intra- and interexamination intraclass correlation coefficients were 0.996-0.998 and coefficients of variation were 1.5%-3.6%. For hepatic MR imaging PDFF, intra- and interexamination intraclass correlation coefficients were greater than or equal to 0.994 and coefficients of variation were less than or equal to 7.3%. In the regression analyses of manual versus semiautomated volume and spectroscopy versus MR imaging, PDFF slopes and intercepts were close to the identity line, and correlations of determination at multivariate analysis (R 2 ) ranged from 0.744 to 0.994. Conclusion This MR imaging-based, semiautomated method provides high repeatability and accuracy for estimating abdominal adipose tissue and thigh muscle volumes and hepatic PDFF. © RSNA, 2017.

Serum Glycine Is Associated with Regional Body Fat and Insulin Resistance in Functionally-Limited Older Adults

USDA-ARS?s Scientific Manuscript database

Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance. The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respec...

(n-3) Fatty Acids Alleviate Adipose Tissue Inflammation and Insulin Resistance: Mechanistic Insights12

PubMed Central

Kalupahana, Nishan S.; Claycombe, Kate J.; Moustaid-Moussa, Naima

2011-01-01

Obesity is associated with the metabolic syndrome, a significant risk factor for developing type 2 diabetes and cardiovascular diseases. Chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metabolic syndrome. Although the exact trigger of this inflammatory process is unknown, adipose tissue hypoxia, endoplasmic reticular stress, and saturated fatty acid–mediated activation of innate immune processes have been identified as important processes in these disorders. Furthermore, macrophages and T lymphocytes have important roles in orchestrating this immune process. Although energy restriction leading to weight loss is the primary dietary intervention to reverse these obesity-associated metabolic disorders, other interventions targeted at alleviating adipose tissue inflammation have not been explored in detail. In this regard, (n-3) PUFA of marine origin both prevent and reverse high-fat-diet–induced adipose tissue inflammation and insulin resistance in rodents. We provide an update on the pathogenesis of adipose tissue inflammation and insulin resistance in obesity and discuss potential mechanisms by which (n-3) PUFA prevent and reverse these changes and the implications in human health. PMID:22332072

Adipocytes impair efficacy of antiretroviral therapy.

PubMed

Couturier, Jacob; Winchester, Lee C; Suliburk, James W; Wilkerson, Gregory K; Podany, Anthony T; Agarwal, Neeti; Xuan Chua, Corrine Ying; Nehete, Pramod N; Nehete, Bharti P; Grattoni, Alessandro; Sastry, K Jagannadha; Fletcher, Courtney V; Lake, Jordan E; Balasubramanyam, Ashok; Lewis, Dorothy E

2018-06-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

PubMed

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

Adipocytes Impair Efficacy of Antiretroviral Therapy

PubMed Central

Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

2018-01-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet.

PubMed

Peixoto, Thamara C; Moura, Egberto G; de Oliveira, Elaine; Soares, Patrícia N; Guarda, Deysla S; Bernardino, Dayse N; Ai, Xu Xue; Rodrigues, Vanessa da S T; de Souza, Gabriela Rodrigues; da Silva, Antonio Jorge Ribeiro; Figueiredo, Mariana S; Manhães, Alex C; Lisboa, Patrícia C

2017-05-13

Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed. HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

PubMed

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Identification of Regulatory Elements That Control PPARγ Expression in Adipocyte Progenitors

PubMed Central

Chou, Wen-Ling; Galmozzi, Andrea; Partida, David; Kwan, Kevin; Yeung, Hui; Su, Andrew I.; Saez, Enrique

2013-01-01

Adipose tissue renewal and obesity-driven expansion of fat cell number are dependent on proliferation and differentiation of adipose progenitors that reside in the vasculature that develops in coordination with adipose depots. The transcriptional events that regulate commitment of progenitors to the adipose lineage are poorly understood. Because expression of the nuclear receptor PPARγ defines the adipose lineage, isolation of elements that control PPARγ expression in adipose precursors may lead to discovery of transcriptional regulators of early adipocyte determination. Here, we describe the identification and validation in transgenic mice of 5 highly conserved non-coding sequences from the PPARγ locus that can drive expression of a reporter gene in a manner that recapitulates the tissue-specific pattern of PPARγ expression. Surprisingly, these 5 elements appear to control PPARγ expression in adipocyte precursors that are associated with the vasculature of adipose depots, but not in mature adipocytes. Characterization of these five PPARγ regulatory sequences may enable isolation of the transcription factors that bind these cis elements and provide insight into the molecular regulation of adipose tissue expansion in normal and pathological states. PMID:24009687

Total and Regional Adiposity and Cognitive Change in Older Adults: The Health, Aging, and Body Composition study

PubMed Central

Kanaya, Alka M.; Lindquist, Karla; Harris, Tamara B.; Launer, Lenore; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

2009-01-01

Objective: Whether total and regional adiposity measured by anthropometry and radiographic studies influences cognitive decline in older adults and whether this association is explained by hormones and inflammatory factors known to be secreted by adipose tissue. Design: Prospective cohort study Setting: Two clinical centers; Pittsburgh, PA and Memphis, TN Participants: 3,054 elders enrolled in the Health, Aging and Body Composition Study. Adiposity measures included BMI, waist circumference, sagittal diameter, total fat mass by DEXA, subcutaneous and visceral fat by abdominal CT. We examined the association between baseline body fat measures and change in 3MS score, sequentially adjusting for confounding and mediating variables including comorbid diseases, adipocytokines, and sex hormones. Main Outcome Measure: The Modified Mini-Mental State Examination (3MS) administered at the first, 3rd, 5th, and 8th annual clinical examination. Results: All baseline adiposity measures varied significantly by sex. In mixed effects models, the association between total and regional adiposity and change in 3MS score varied significantly by sex, with the highest adiposity tertile being associated with greater cognitive declines in men (p<0.05 for each adiposity measure) but not in women (p-for-interaction<0.05). Total fat mass was significantly associated with greater change in 3MS score among men (lowest tertile −1.5, middle tertile −2.4, highest tertile −2.6, p-for-trend=0.005) even after adjusting for mediators. Conclusions: Higher levels of all adiposity measures were associated with worsening cognitive function in men after controlling for metabolic disorders, adipocytokines and sex hormone levels. Conversely, there was no association between adiposity and cognitive change in women. PMID:19273751

Adipose-derived stem cells and periodontal tissue engineering.

PubMed

Tobita, Morikuni; Mizuno, Hiroshi

2013-01-01

Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

PubMed

Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

2017-01-01

To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

Improved fat graft survival by different volume fractions of platelet-rich plasma and adipose-derived stem cells.

PubMed

Li, Feng; Guo, Weihua; Li, Kun; Yu, Mei; Tang, Wei; Wang, Hang; Tian, Weidong

2015-03-01

The success of soft-tissue augmentation is offset by the low survival rates of grafted fat tissue. Research shows that adipose-derived stem cells (ASCs) and platelet-rich plasma (PRP) are beneficial to tissue healing. To evaluate the long-term effects of different volume fractions of PRP combined with ASCs on fat graft. ASCs were isolated from human fat tissue, and PRP was obtained from human blood. Cell count kit-8 and real-time polymerase chain reaction (PCR) were used to evaluate the influence of PRP (0%, 10%, 20%, and 30%; volume/volume [v/v]) in medium on ASC proliferation and adipogenic differentiation, respectively. A novel lipoinjection consisting of granular fat, PRP, and ASCs was subcutaneously transplanted into nude mice. The grafts were volumetrically and histologically evaluated 10, 30, 60, and 90 days after transplantation. The addition of PRP improved ASC proliferation. Expression of adipogenic-related genes, peroxisome proliferator-activated receptor-γ, lipoprotein lipase, and adipophilin were up-regulated in PRP-induced ASCs. Compared with other groups, granular fat grafts formed with 20% (v/v) and 30% (v/v) PRP significantly improved residual volumes. More intact adipocytes and capillary formation, but less vacuolization, were observed in the 20% (v/v) and 30% (v/v) PRP groups at 30, 60, and 90 days. However, no significant difference was observed between the 20% (v/v) and 30% (v/v) PRP groups in retaining fat grafts and improving histology. Fat grafting with 20% (v/v) PRP and ASCs constitutes an appropriate transplantation strategy for improving graft survival and provides a potential approach for soft-tissue restoration in plastic and reconstructive surgery. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Differential Effects of Dietary Fat Content and Protein Source on Bone Phenotype and Fatty Acid Oxidation in Female C57Bl/6 Mice

PubMed Central

Sawin, Emily A.; Stroup, Bridget M.; Murali, Sangita G.; O’Neill, Lucas M.; Ntambi, James M.

2016-01-01

Background Glycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide released from κ-casein during cheesemaking that promotes satiety, reduces body fat, increases bone mass and infers prebiotic and anti-inflammatory effects. The impact of adiposity and gender on bone health is unclear. Objective To determine how feeding female mice diets providing 60% Fat Kcal (high-fat) or 13% Fat Kcal (control) with either GMP or casein as the protein source impacts: body composition, ex vivo fatty acid oxidation, bone (femoral) biomechanical performance, and the relationship between body composition and bone. Methods Weanling female C57Bl/6 mice were fed high-fat (60% Fat Kcal) or control diets (13% Fat Kcal) with GMP or casein from 3 to 32 weeks of age with assessment of body weight and food intake. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Fatty acid oxidation was measured in liver, muscle, and fat tissues using 14C-palmitate. Plasma concentrations of hormones and cytokines were determined. Bone biomechanical performance was assessed by the 3-point bending test. Results Female mice fed high-fat diets showed increased fatty acid oxidation capacity in both gastrocnemius muscle and brown adipose tissue compared to mice fed the control diets with a lower fat content. Despite increased fat mass in mice fed the high-fat diets, there was little evidence of glucose impairment or inflammation. Mice fed the high-fat diets had significantly greater total body bone mineral density (BMD), femoral BMD, and femoral cross-sectional area than mice fed the control diets. Femora of mice fed the high-fat diets had increased yield load and maximum load before fracture, consistent with greater bone strength, but reduced post-yield displacement or ductility, consistent with bone brittleness. Female mice fed a high-fat GMP diet displayed increased fat oxidation capacity in subcutaneous fat relative to mice fed the high-fat casein diet. Regardless of dietary fat content, GMP increased total body bone mineral content and femur length. The prebiotic properties of GMP may mediate the beneficial effects of GMP on bone. Conclusions Female mice adapt to high-fat feeding by increasing oxidative capacity in muscle tissue and to a lesser extent brown adipose tissue. High-fat feeding in female mice leads to development of a bone phenotype where femora show increased BMD and are stronger, yet more brittle. The increased brittleness of bone was associated with increased body fat content due to high-fat feeding. In summary, high-fat feeding in female mice increases mineralization of bone, but negatively impacts bone quality resulting in brittle bones. PMID:27695036

Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Frühbeck, Gema

2011-01-01

Aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) encompass a subfamily of aquaporins that allow the movement of water and other small solutes, especially glycerol, through cell membranes. Adipose tissue constitutes a major source of glycerol via AQP7. We have recently reported that, in addition to the well-known expression of AQP7 in adipose tissue, AQP3 and AQP9 are also expressed in omental and subcutaneous fat depots. Moreover, insulin and leptin act as regulators of aquaglyceroporins through the PI3K/Akt/mTOR pathway. AQP3 and AQP7 appear to facilitate glycerol efflux from adipose tissue while reducing the glycerol influx into hepatocytes via AQP9 to prevent the excessive lipid accumulation and the subsequent aggravation of hyperglycemia in human obesity. This Extra View focuses on the control of glycerol release by aquaglyceroporins in the adipose tissue and briefly discusses the importance of glycerol as a substrate for hepatic gluconeogenesis, pancreatic insulin secretion and cardiac ATP production. PMID:21502813

Adipose-derived mesenchymal stem cells from liposuction and resected fat are feasible sources for regenerative medicine.

PubMed

Schneider, Sandra; Unger, Marina; van Griensven, Martijn; Balmayor, Elizabeth R

2017-05-19

The use of mesenchymal stem cells (MSCs) in research and in regenerative medicine has progressed. Bone marrow as a source has drawbacks because of subsequent morbidities. An easily accessible and valuable source is adipose tissue. This type of tissue contains a high number of MSCs, and obtaining higher quantities of tissue is more feasible. Fat tissue can be harvested using different methods such as liposuction and resection. First, a detailed isolation protocol with complete characterization is described. This also includes highlighting problems and pitfalls. Furthermore, some comparisons of these different harvesting methods exist. However, the later characterization of the cells is conducted poorly in most cases. We performed an in-depth characterization over five passages including an investigation of the effect of freezing and thawing. Characterization was performed using flow cytometry with CD markers, metabolic activity with Alamar Blue, growth potential in between passages, and cytoskeleton staining. Our results show that the cells isolated with distinct isolation methods (solid versus liposuction "liquid") have the same MSC potential. However, the percentage of cells positive for the markers CD73, CD90, and CD105 is initially quite low. The cells isolated from the liquid fat tissue grow faster at higher passages, and significantly more cells display MSC markers. In summary, we show a simple and efficient method to isolate adipose-derived mesenchymal stem cells from different preparations. Liposuctions and resection can be used, whereas liposuction has more growth potential at higher passages.

Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

USDA-ARS?s Scientific Manuscript database

Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

Preclinical In vivo Imaging for Fat Tissue Identification, Quantification, and Functional Characterization.

PubMed

Marzola, Pasquina; Boschi, Federico; Moneta, Francesco; Sbarbati, Andrea; Zancanaro, Carlo

2016-01-01

Localization, differentiation, and quantitative assessment of fat tissues have always collected the interest of researchers. Nowadays, these topics are even more relevant as obesity (the excess of fat tissue) is considered a real pathology requiring in some cases pharmacological and surgical approaches. Several weight loss medications, acting either on the metabolism or on the central nervous system, are currently under preclinical or clinical investigation. Animal models of obesity have been developed and are widely used in pharmaceutical research. The assessment of candidate drugs in animal models requires non-invasive methods for longitudinal assessment of efficacy, the main outcome being the amount of body fat. Fat tissues can be either quantified in the entire animal or localized and measured in selected organs/regions of the body. Fat tissues are characterized by peculiar contrast in several imaging modalities as for example Magnetic Resonance Imaging (MRI) that can distinguish between fat and water protons thank to their different magnetic resonance properties. Since fat tissues have higher carbon/hydrogen content than other soft tissues and bones, they can be easily assessed by Computed Tomography (CT) as well. Interestingly, MRI also discriminates between white and brown adipose tissue (BAT); the latter has long been regarded as a potential target for anti-obesity drugs because of its ability to enhance energy consumption through increased thermogenesis. Positron Emission Tomography (PET) performed with 18 F-FDG as glucose analog radiotracer reflects well the metabolic rate in body tissues and consequently is the technique of choice for studies of BAT metabolism. This review will focus on the main, non-invasive imaging techniques (MRI, CT, and PET) that are fundamental for the assessment, quantification and functional characterization of fat deposits in small laboratory animals. The contribution of optical techniques, which are currently regarded with increasing interest, will be also briefly described. For each technique the physical principles of signal detection will be overviewed and some relevant studies will be summarized. Far from being exhaustive, this review has the purpose to highlight some strategies that can be adopted for the in vivo identification, quantification, and functional characterization of adipose tissues mainly from the point of view of biophysics and physiology.

Gut REG3γ-Associated Lactobacillus Induces Anti-inflammatory Macrophages to Maintain Adipose Tissue Homeostasis

PubMed Central

Huang, Yugang; Qi, HouBao; Zhang, Zhiqian; Wang, Enlin; Yun, Huan; Yan, Hui; Su, Xiaomin; Liu, Yingquan; Tang, Zenzen; Gao, Yunhuan; Shang, Wencong; Zhou, Jiang; Wang, Tianze; Che, Yongzhe; Zhang, Yuan; Yang, Rongcun

2017-01-01

Gut microbiota may not only affect composition of local immune cells but also affect systemic immune cells. However, it is not completely clear how gut microbiota modulate these immune systems. Here, we found that there exist expanded macrophage pools in huREG3γtgIEC mice. REG3γ-associated Lactobacillus, which is homology to Lactobacillus Taiwanese, could enlarge macrophage pools not only in the small intestinal lamina propria but also in the spleen and adipose tissues. STAT3-mediated signal(s) was a critical factor in the Lactobacillus-mediated anti-inflammatory macrophages. We also offered evidence for critical cellular links among REG3γ-associated Lactobacillus, tissue macrophages, and obesity diseases. Anti-inflammatory macrophages in the lamina propria, which are induced by REG3γ-associated Lactobacillus, may migrate into adipose tissues and are involved in resistance against high-fat diet-mediated obesity. Thus, REG3γ-associated Lactobacillus-induced anti-inflammatory macrophages in gut tissues may play a role in adipose tissue homeostasis. PMID:28928739