Multiorgan insulin sensitivity in lean and obese subjects.

PubMed

Conte, Caterina; Fabbrini, Elisa; Kars, Marleen; Mittendorfer, Bettina; Patterson, Bruce W; Klein, Samuel

2012-06-01

To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m(2), mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m(2)) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. In obese subjects, palmitate and glucose R(a) in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose R(a) was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate R(a) (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate R(a) and glucose R(a) were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose R(d) was greater in lean than obese subjects across the entire physiological range of plasma insulin. Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.

Genetic interaction of DGAT2 and FAAH in the development of human obesity.

PubMed

Ning, Tinglu; Zou, Yaoyu; Yang, Minglan; Lu, Qianqian; Chen, Maopei; Liu, Wen; Zhao, Shaoqian; Sun, Yingkai; Shi, Juan; Ma, Qinyun; Hong, Jie; Liu, Ruixin; Wang, Jiqiu; Ning, Guang

2017-05-01

DGAT2 is the critical catalyzing enzyme for triglyceride biosynthesis, and excess triglyceride accumulation in fat tissues is a fundamental process for obesity. Mutations in DGAT2 or other genes interacting with DGAT2 associated with adiposity have not been reported in human to date. DGAT2 mutation was identified based on our in-home database-exome sequencing 227 young obese subjects (body-mass index (BMI), 35.1-61.7 kg/m 2 ) and 219 lean controls (BMI, 17.5-23.0 kg/m 2 ), further validated in 1190 lean subjects and the pedigree of the proband. The trios of the proband were further subjected to whole-exome sequencing to explore the candidate genes for obesity. The mutations in DGAT2 and FAAH were functionally evaluated in vitro. We detected two rare variants in DGAT2 with no significant difference between obese and lean individuals. One novel heterozygous nonsense variant c.382C > T (p.R128*) was identified in one obese subject but not in 219 lean subjects and another 1190 lean subjects. Notably, in vitro study showed that R128* mutation severely damaged the TG-biosynthesis ability of DGAT2, and all other R128* carriers in the pedigree were lean. Thus, we further identified a loss-of-function variant c. 944G > T (p.R315I) in FAAH in the proband inheriting from his obese father. Importantly, FAAH overexpression inhibited DGAT2 expression and TG synthesis, while R315I mutant largely eliminated this inhibitory effect. We first report loss-of-function mutations in DGAT2 and FAAH in one obese subject, which may interact with each other to affect the adiposity penetrance, providing a model of genetic interaction associated with human obesity.

Challenges in simulating the human gut for understanding the role of the microbiota in obesity.

PubMed

Aguirre, M; Venema, K

2017-02-07

There is an elevated incidence of cases of obesity worldwide. Therefore, the development of strategies to tackle this condition is of vital importance. This review focuses on the necessity of optimising in vitro systems to model human colonic fermentation in obese subjects. This may allow to increase the resolution and the physiological relevance of the information obtained from this type of studies when evaluating the potential role that the human gut microbiota plays in obesity. In light of the parameters that are currently used for the in vitro simulation of the human gut (which are mostly based on information derived from healthy subjects) and the possible difference with an obese condition, we propose to revise and improve specific standard operating procedures.

Evaluation of plasma reactive oxygen metabolites levels in obese subjects with periodontal disease.

PubMed

Suresh, Snophia; Mahendra, Jaideep; Sudhakar, Uma; Pradeep, A R; Singh, Gurdeep

2016-01-01

Obesity represents the systemic condition capable of influencing the onset and progression of periodontal disease. Obesity is associated with oxidative stress. Plasma level of reactive oxidative metabolites (ROMs) is measured as an indicator of oxidative stress in the body. The aim of this study is to assess and compare the plasma ROM levels in obese subjects with healthy and inflammatory periodontal status. Sixty subjects selected were grouped as 15 obese or overweight subjects with generalized chronic periodontitis, 15 obese or overweight subjects with generalized chronic gingivitis, 15 obese or overweight subjects with healthy periodontium, and 15 nonobese and healthy periodontium. The clinical periodontal parameters such as plaque index, gingival index, probing pocket depth, and clinical attachment level were measured. Blood samples were obtained to measure the plasma levels of ROM. In this study, obese subjects with chronic periodontitis (Group I) had mean plasma ROM levels (442.3 ± 15.65 Carratelli unit [CARR U]) showing 100% subjects with high oxidative stress. Obese subjects with chronic gingivitis (Group II) had mean plasma ROM levels (358.7 ± 20.61 CARR U) indicating 86.7% subjects with oxidative stress. Obese subjects with healthy periodontium (Group III) had 46.7% subjects with slight oxidative stress, and the mean ROM level was 320.2 ± 17.57. Nonobese subjects with healthy periodontium (Group IV) had 80% of subjects with normal oxidative stress and the mean plasma ROM level was 296.9 ± 20.35 CARR U. The intra- and inter-group comparison showed significant difference (P < 0.001). From our study, we report that obese subjects with periodontitis have more oxidative stress compared to obese subjects with healthy periodontium.

Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes.

PubMed

Gómez-Ambrosi, Javier; Pascual, Eider; Catalán, Victoria; Rodríguez, Amaia; Ramírez, Beatriz; Silva, Camilo; Gil, María J; Salvador, Javier; Frühbeck, Gema

2014-10-01

Betatrophin is a secreted protein recently involved in β-cell replication with a potential role in type 2 diabetes mellitus (T2D). The aim of the present study was to compare the circulating concentrations of betatrophin in human obesity and T2D. Serum concentrations of betatrophin were measured by ELISA in 153 subjects: 75 obese normoglycemic subjects (OB-NG), 30 obese subjects with impaired glucose tolerance (OB-IGT), and 15 obese subjects with T2D (OB-T2D) matched by sex, age, and body adiposity, in comparison with 33 lean normoglycemic individuals (LN-NG). Circulating levels of betatrophin were significantly decreased in obese individuals and further diminished in IGT and T2D participants (LN-NG, 45.1 ± 24.4 ng/mL; OB-NG, 26.9 ± 15.4 ng/mL; OB-IGT, 18.3 ± 10.7 ng/mL; OB-T2D, 13.5 ± 8.8 ng/mL; P < .001). A marked sexual dimorphism was found, with betatrophin levels being significantly higher in women than in men (males, 21.1 ± 16.0 ng/mL; females, 34.1 ± 20.1 ng/mL; P < .001). Interestingly, betatrophin levels were positively correlated with the quantitative insulin sensitivity check index (r = 0.46; P < .001) and with high-density lipoprotein-cholesterol concentrations (r = 0.51; P < .001). We conclude that serum betatrophin is decreased in human obesity, being further reduced in obesity-associated insulin resistance. Betatrophin levels are closely related to obesity-associated cardiometabolic risk factors, emerging as a potential biomarker of insulin resistance and T2D.

The l-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity

PubMed Central

Moreno-Navarrete, José María; Catalán, Victoria; Whyte, Lauren; Díaz-Arteaga, Adenis; Vázquez-Martínez, Rafael; Rotellar, Fernando; Guzmán, Rocío; Gómez-Ambrosi, Javier; Pulido, Marina R.; Russell, Wendy R.; Imbernón, Mónica; Ross, Ruth A.; Malagón, María M.; Dieguez, Carlos; Fernández-Real, José Manuel; Frühbeck, Gema; Nogueiras, Ruben

2012-01-01

GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. PMID:22179809

Intraduodenal Administration of Intact Pea Protein Effectively Reduces Food Intake in Both Lean and Obese Male Subjects

PubMed Central

Geraedts, Maartje C. P.; Troost, Freddy J.; Munsters, Marjet J. M.; Stegen, Jos H. C. H.; de Ridder, Rogier J.; Conchillo, Jose M.; Kruimel, Joanna W.; Masclee, Ad A. M.; Saris, Wim H. M.

2011-01-01

Background Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects. Methods Ten lean (BMI:23.0±0.7 kg/m2) and ten obese (BMI:33.4±1.4 kg/m2) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded. Results CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA. Conclusions Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity. PMID:21931864

Attenuated thermoregulatory responses with increased plasma osmolality in obese subjects during two seasons

NASA Astrophysics Data System (ADS)

Kanikowska, Dominika; Sato, Maki; Sugenoya, Junichi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko; Iwase, Satoshi

2013-09-01

Obese subjects may be more vulnerable to injury from heat stress, and appear to be less efficient at thermoregulation. Sweat rate, tympanic temperature and osmolality in obese subjects were investigated in Japan during two seasons. The purpose of this study was to examine the relationship between obesity, thermoregulatory response and season. Five obese (BMI, 32.0 ± 4.9 kg/m2) and five non-obese (BMI, 23.2 ± 2.9 kg/m2) men participated in this experiment at latitude 35°10' N and longitude 136°57.9'E. The average atmospheric temperature was 29.1 ± 1.0 °C in summer and 3.3 ± 1.4 °C in winter. Tympanic temperature and sweat rate were measured during leg water immersion at 42 °C for 30 min. Blood samples were analyzed for plasma osmolality. The relationship between tympanic temperature and sweat rate decreased significantly in obese compared to in non-obese subjects in both seasons, there being a lowered sweat rate for any core temperature in obese subjects. Plasma osmolality was significantly higher in obese than in non-obese subjects in both seasons. Thermal sensation increased significantly in non-obese than in obese in winter but not in summer. Our data show that thermoregulatory responses are attenuated in obese subjects compared with controls, suggesting that obese people are at increased risk of heat-related illnesses.

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence.

PubMed

Harvie, Michelle; Howell, Anthony

2017-01-19

Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.

Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans.

PubMed

Baker, Peter R; Boyle, Kristen E; Koves, Timothy R; Ilkayeva, Olga R; Muoio, Deborah M; Houmard, Joseph A; Friedman, Jacob E

2015-05-01

Investigate the effects of obesity and high-fat diet (HFD) exposure on fatty acid oxidation and TCA cycle intermediates and amino acids in skeletal muscle to better characterize energy metabolism. Plasma and skeletal muscle metabolomic profiles were measured from lean and obese males before and after a 5-day HFD in the 4 h postprandial condition. At both time points, plasma short-chain acylcarnitine species (SCAC) were higher in the obese subjects, while the amino acids glycine, histidine, methionine, and citrulline were lower in skeletal muscle of obese subjects. Skeletal muscle medium-chain acylcarnitines (MCAC) C6, C8, C10:2, C10:1, C10, and C12:1 increased in obese subjects, but decreased in lean subjects, from pre- to post-HFD. Plasma content of C10:1 was also decreased in the lean but increased in the obese subjects from pre- to post-HFD. CD36 increased from pre- to post-HFD in obese but not lean subjects. Lower skeletal muscle amino acid content and accumulation of plasma SCAC in obese subjects could reflect increased anaplerosis for TCA cycle intermediates, while accumulation of MCAC suggests limitations in β-oxidation. These measures may be important markers of or contributors to dysregulated metabolism observed in skeletal muscle of obese humans. © 2015 The Obesity Society.

Polygenic obesity in humans.

PubMed

Hinney, Anke; Hebebrand, Johannes

2008-01-01

The molecular genetic analysis of obesity has led to the identification of a limited number of confirmed major genes. While such major genes have a clear influence on the development of the phenotype, the underlying mutations are however (extremely) infrequent and thus of minor clinical importance only. The genetic predisposition to obesity must thus be polygenic; a number of such variants should be found in most obese subjects; however, these variants predisposing to obesity are also found in normal weight and even lean individuals. Therefore, a polygene can only be identified and validated by statistical analyses: the appropriate gene variant (allele) occurs more frequently in obese than in non-obese subjects. Each single polygene makes only a small contribution to the development of obesity. The 103Ile allele of the Val103Ile single nucleotide polymorphism (SNP) of the melanocortin-4 receptor gene (MC4R) was the first confirmed polygenetic variant with an influence on the body mass index (BMI); the more common Val103 allele is more frequent in obese individuals. As determined in a recent, large-scaled meta-analysis the effect size of this allele on mean BMI was approximately -0.5 kg/m(2). The first genome-wide association study (GWA) for obesity, based on approximately 100,000 SNPs analyzed in families of the Framingham study, revealed that a SNP in the proximity of the insulin-induced gene 2 (INSIG2) was associated with obesity. The positive result was replicated in independent samples; however, some other study groups detected no association. Currently, a meta-analysis is ongoing; its result will contribute to the evaluation of the importance of the INSIG2 polymorphism in body weight regulation. SNP alleles in intron 1 of the fat mass and obesity associated gene (FTO) confer the most relevant polygenic effect on obesity. In the first GWA for extreme early onset obesity we substantiated that variation in FTO strongly contributes to early onset obesity

Lower-Limb Joint Coordination Pattern in Obese Subjects

PubMed Central

Ranavolo, Alberto; Donini, Lorenzo M.; Mari, Silvia; Serrao, Mariano; Silvetti, Alessio; Iavicoli, Sergio; Cava, Edda; Asprino, Rosa; Pinto, Alessandro; Draicchio, Francesco

2013-01-01

The coordinative pattern is an important feature of locomotion that has been studied in a number of pathologies. It has been observed that adaptive changes in coordination patterns are due to both external and internal constraints. Obesity is characterized by the presence of excess mass at pelvis and lower-limb areas, causing mechanical constraints that central nervous system could manage modifying the physiological interjoint coupling relationships. Since an altered coordination pattern may induce joint diseases and falls risk, the aim of this study was to analyze whether and how coordination during walking is affected by obesity. We evaluated interjoint coordination during walking in 25 obese subjects as well as in a control group. The time-distance parameters and joint kinematics were also measured. When compared with the control group, obese people displayed a substantial similarity in joint kinematic parameters and some differences in the time-distance and in the coupling parameters. Obese subjects revealed higher values in stride-to-stride intrasubjects variability in interjoint coupling parameters, whereas the coordinative mean pattern was unaltered. The increased variability in the coupling parameters is associated with an increased risk of falls and thus should be taken into account when designing treatments aimed at restoring a normal locomotion pattern. PMID:23484078

Convergence of adipocyte hypertrophy, telomere shortening and hypoadiponectinemia in obese subjects and in patients with type 2 diabetes.

PubMed

Monickaraj, Finny; Gokulakrishnan, Kuppan; Prabu, Paramasivam; Sathishkumar, Chandrakumar; Anjana, Ranjit Mohan; Rajkumar, Janavikula Sankaran; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

2012-11-01

Although telomere shortening has been linked with type 2 diabetes and most variables of adiposity, a shortcoming of such studies is the measurement of telomere length in leukocytes. Therefore, we tested the association among adipocyte cell size, telomere length (both subcutaneous and visceral adipose tissue) and systemic levels of adiponectin in obese subjects and patients with type 2 diabetes compared to control subjects. Human subcutaneous and visceral adipose tissues were obtained from the subjects who have undergone bariatric surgery or other abdominal surgeries. The study groups comprised: i) control subjects, ii) type 2 diabetes patients, iii) obese subjects without diabetes and iv) obese subjects with diabetes. Adipocyte cell size was measured by histological staining. Adiponectin levels were measured by ELISA. Telomere length was determined by Real-time PCR and lipid peroxidation was assessed by fluorimetry. Compared to control subjects, adipocyte size (both subcutaneous and visceral) from obese, diabetic and obese-diabetic subjects was significantly larger [p<0.001]. Individuals with adipose hypertrophy also exhibited shortened telomeres and hypoadiponectinemia. Pearson correlation analysis revealed that both visceral and subcutaneous fat cell size showed a positive correlation with FBS, HbA1c, HOMA-IR, LDL, total cholesterol, triglycerides and negatively correlated with HDL and adiponectin. Regression analysis revealed that the association between shortened telomeres and hypoadiponectinemia was lost when adjusted for adipocyte cell size. Adipocyte hypertrophy appears to be strongly associated with shortened telomeres, hypoadiponectinemia and poor glycemic and lipid control. Interestingly, these molecular alterations seen in lean diabetics reflect a state of 'metabolic obesity'. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Medical implications of obesity in horses--lessons for human obesity.

PubMed

Johnson, Philip J; Wiedmeyer, Charles E; Messer, Nat T; Ganjam, Venkataseshu K

2009-01-01

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. © Diabetes Technology Society

Medical Implications of Obesity in Horses—Lessons for Human Obesity

PubMed Central

Johnson, Philip J.; Wiedmeyer, Charles E.; Messer, Nat T.; Ganjam, Venkataseshu K.

2009-01-01

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. PMID:20046661

Effect of Dark Chocolate Extracts on Phorbol 12-Myristate 13-Acetate-Induced Oxidative Burst in Leukocytes Isolated by Normo-Weight and Overweight/Obese Subjects

PubMed Central

Ioannone, Francesca; Sacchetti, Giampiero; Serafini, Mauro

2017-01-01

Oxidative and inflammatory stress represents a major risk factor for cardiovascular disease (CVD) in overweight and obese subjects. Between the different plant foods, chocolate has been shown to decrease CVD risk due to its antioxidant and anti-inflammatory properties. However, as we recently showed in epidemiological studies, meta-analyses, and human trials, dietary antioxidants resulted more effective in subjects characterized by an ongoing oxidative stress, than in healthy people. Aim of this work was to investigate the effect of different concentrations of chocolate phenolic extract (CPE) on in vitro free radical production, stimulated by phorbol 12-myristate 13-acetate (PMA), in leukocytes extracted from blood of normo-weight and overweight/obese subjects. Neutrophils from overweight/obese group had a significantly higher free radical production compared to the normo-weight group. In neutrophils, the lowest CPE concentration significantly reduced free radical production in overweight/obese group only, and higher CPE concentrations were effective in both groups. In monocytes, the CPE concentration that was significantly effective in reducing free radical production was lower in overweight/obese subjects than in normo-weight subjects. Chocolate polyphenol extracts inhibit oxidative burst in human neutrophils and monocytes with a higher efficiency in subjects characterized by an unphysiological oxidative/inflammatory stress, such as overweight and obese. Results of this study provide further evidence about a differential role of dietary antioxidant strictly related to the “stress” condition of the subjects. PMID:28649567

Effect of Dark Chocolate Extracts on Phorbol 12-Myristate 13-Acetate-Induced Oxidative Burst in Leukocytes Isolated by Normo-Weight and Overweight/Obese Subjects.

PubMed

Ioannone, Francesca; Sacchetti, Giampiero; Serafini, Mauro

2017-01-01

Oxidative and inflammatory stress represents a major risk factor for cardiovascular disease (CVD) in overweight and obese subjects. Between the different plant foods, chocolate has been shown to decrease CVD risk due to its antioxidant and anti-inflammatory properties. However, as we recently showed in epidemiological studies, meta-analyses, and human trials, dietary antioxidants resulted more effective in subjects characterized by an ongoing oxidative stress, than in healthy people. Aim of this work was to investigate the effect of different concentrations of chocolate phenolic extract (CPE) on in vitro free radical production, stimulated by phorbol 12-myristate 13-acetate (PMA), in leukocytes extracted from blood of normo-weight and overweight/obese subjects. Neutrophils from overweight/obese group had a significantly higher free radical production compared to the normo-weight group. In neutrophils, the lowest CPE concentration significantly reduced free radical production in overweight/obese group only, and higher CPE concentrations were effective in both groups. In monocytes, the CPE concentration that was significantly effective in reducing free radical production was lower in overweight/obese subjects than in normo-weight subjects. Chocolate polyphenol extracts inhibit oxidative burst in human neutrophils and monocytes with a higher efficiency in subjects characterized by an unphysiological oxidative/inflammatory stress, such as overweight and obese. Results of this study provide further evidence about a differential role of dietary antioxidant strictly related to the "stress" condition of the subjects.

Nitrogen loss in normal and obese subjects during total fast.

PubMed

Göschke, H; Stahl, M; Thölen, H

1975-07-01

Healthy volunteers of ideal weight (12 men and 12 women) were fasted for 6 days, and obese but otherwise healthy subjects (20 men, 28 women) for 6--28 days. In all groups studied a significant increase in urinary nitrogen loss from day 1 to day 3 of fasting was followed by a steady decrease. The early rise in urinary nitrogen excretion coincided with a rise in plasma glucagon levels, suggesting a relation of the latter to increased gluconeogenesis from amino acids. At equal weight greater nitrogen losses were found in men than in women, in both normal and obese subjects. In spite of much higher weight and larger energy expenditure and nitrogen loss in obese subjects however was not higher than in normal ones. Mean daily nitrogen losses varied from 14.5 g (normal and obese men early in starvation) to 3.0 g (obese women after a 4-weeks fast). Calculating the amount of calories derived from body protien (urinary nitrogen X 6.25 X 4.1)and taking total energy expenditure from tabular metabolic values, the contribution of protein to total calorie output was found to vary from 15% (normal men 6 day fast) to 5(obese women, 4th week of fasting). The clinical significance of nitrogen loss during therapeutic fasting is discussed.

Endocannabinoids Measurement in Human Saliva as Potential Biomarker of Obesity

PubMed Central

Tabarin, Antoine; Clark, Samantha; Leste-Lasserre, Thierry; Marsicano, Giovanni; Piazza, Pier Vincenzo; Cota, Daniela

2012-01-01

Background The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss. Methodology/Principal Findings Fasting plasma and salivary endocannabinoids and N-acylethanolamines were measured through liquid mass spectrometry in 12 normal weight and 12 obese, insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines were evaluated in the same cohort before and after the consumption of a meal. Changes in salivary endocannabinoids and N-acylethanolamines after body weight loss were investigated in a second group of 12 obese subjects following a 12-weeks lifestyle intervention program. The levels of mRNAs coding for enzymes regulating the metabolism of endocannabinoids, N-acylethanolamines and of cannabinoid type 1 (CB1) receptor, alongside endocannabinoids and N-acylethanolamines content, were assessed in human salivary glands. The endocannabinoids 2-arachidonoylglycerol (2-AG), N-arachidonoylethanolamide (anandamide, AEA), and the N-acylethanolamines (oleoylethanolamide, OEA and palmitoylethanolamide, PEA) were quantifiable in saliva and their levels were significantly higher in obese than in normal weight subjects. Fasting salivary AEA and OEA directly correlated with BMI, waist circumference and fasting insulin. Salivary endocannabinoids and N-acylethanolamines did not change in response to a meal. CB1 receptors, ligands and enzymes were expressed in the salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks lifestyle program significantly decreased salivary AEA levels. Conclusions

The effect of covert changes in energy density of preloads on subsequent ad libitum energy intake in lean and obese human subjects.

PubMed

Durrant, M L; Royston, J P; Wloch, R T; Garrow, J S

1982-01-01

1. Covert changes in energy intake were made by giving preloads of disguised energy density three times daily to 14 obese and 6 lean subjects. 2. The preloads contained 2.51 MJ (600 kcal)/d on days 2 and 3 and either 3.77 MJ (900 kcal)/d or 1.26 MJ (300 kcal/d) on days 4 and 5 and 1.26 MJ (300 kcal)/d or 3.77 MJ (900 kcal)/d on days 6 and 7. The order of testing was alternated for each subject. 3. Subsequent energy intake at each meal (lunch, dinner and breakfast) was measured with an automated food-dispensing machine. 4. Overall the obese subjects ate significantly less from the machine, 3.28 +/- 1.89 MJ (785 +/- 452 kcal)/d, than the lean subjects, 6.03 +/- 1.26 MJ (1442 +/- 300 kcal)/d. 5. Both groups of subjects adjusted their energy intake in the right direction to counterbalance the effect of the preloads but the lean subjects changed their intake by an average of 0.74 MJ (176 kcal)/d compared with the obese subjects who changed their intake by an average of 0.29 MJ (70 kcal)/d. 6. Although the lean subjects were better at adjusting their energy intake than the obese subjects, regulation was still imprecise relative to the 2.51 MJ (600 kcal)/d difference in energy intake that was imposed. 7. There were no significant differences in hunger or appetite between subjects or test situations.

Health-Related Quality of Life and Quality of Sexual Life in Obese Subjects

PubMed Central

Di Lazzaro, Luca; Pinto, Alessandro; Migliaccio, Silvia; Lenzi, Andrea; Donini, Lorenzo M.

2014-01-01

The increased prevalence of obesity represents, currently, one of the major public health issues, due to its consequences on physical and psychological health status as well as on the psychosocial functioning. As defined by the World Health Organization, sexual health is “a state of physical, emotional, mental, and social well-being in relation to sexuality.” The aim of the present study was to explore the relationship between sexual life in obese subjects and quality of life, psychological status, and disability. Methods. 95 obese subjects were recruited from June 2012 to February 2013 and underwent physical examination and measures for the assessment of quality of life, sexual life, psychological status, and disability. Results. In obese subjects sexual life was related to gender, age, psychological status, disability, and quality of life. Conclusion. As obesity is a multifactorial disease, and is accompanied by multiple comorbidities, it is difficult to identify a single causative factor responsible for the impairment of sexual life in obese subjects; thus, a thorough, multidimensional evaluation including sexual function assessment should be performed in obese people. PMID:24707290

Micronutrient deficiency in obese subjects undergoing low calorie diet

PubMed Central

2012-01-01

Background The prevalence of micronutrient deficiencies is higher in obese individuals compared to normal-weight people, probably because of inadequate eating habits but also due to increased demands among overweight persons, which are underestimated by dietary reference intakes (DRI) intended for the general population. We therefore evaluated the dietary micronutrient intake in obese individuals compared to a reference population and DRI recommendations. Furthermore, we determined the micronutrient status in obese subjects undergoing a standardized DRI-covering low-calorie formula diet to analyze if the DRI meet the micronutrient requirements of obese individuals. Methods In 104 subjects baseline micronutrient intake was determined by dietary record collection. A randomly assigned subgroup of subjects (n = 32) underwent a standardized DRI-covering low-calorie formula diet over a period of three months. Pre- and post-interventional intracellular micronutrient status in buccal mucosa cells (BMC) was analyzed, as well as additional micronutrient serum concentrations in 14 of the subjects. Results Prior to dietetic intervention, nutrition was calorie-rich and micronutrient-poor. Baseline deficiencies in serum concentrations were observed for 25-hydroxyvitamin-D, vitamin C, selenium, iron, as well as ß-carotene, vitamin C, and lycopene in BMC. After a three-month period of formula diet even more subjects had reduced micronutrient levels of vitamin C (serum, BMC), zinc, and lycopene. There was a significant negative correlation between lipophilic serum vitamin concentrations and body fat, as well as between iron and C-reactive protein. Conclusions The present pilot study shows that micronutrient deficiency occurring in obese individuals is not corrected by protein-rich formula diet containing vitamins and minerals according to DRI. In contrast, micronutrient levels remain low or become even lower, which might be explained by insufficient intake, increased demand

Sensory and non-sensory factors and the concept of externality in obese subjects.

PubMed

Gardner, R M; Brake, S J; Reyes, B; Maestas, D

1983-08-01

9 obese and 9 normal subjects performed a psychophysical task in which food- or non-food-related stimuli were briefly flashed tachistoscopically at a speed and intensity near the visual threshold. A signal was presented on one-half the trials and noise only on the other one-half of the trials. Using signal detection theory methodology, separate measures of sensory sensitivity (d') and response bias (beta) were calculated. No differences were noted between obese and normal subjects on measures of sensory sensitivity but significant differences on response bias. Obese subjects had consistently lower response criteria than normal ones. Analysis for subjects categorized by whether they were restrained or unrestrained eaters gave findings identical to those for obese and normal. The importance of using a methodology that separates sensory and non-sensory factors in research on obesity is discussed.

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training

PubMed Central

La Favor, Justin D.; Dubis, Gabriel S.; Yan, Huimin; White, Joseph D.; Nelson, Margaret A.M.; Anderson, Ethan J.; Hickner, Robert C.

2016-01-01

Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies. PMID:27765769

Study of the regulation by nutrients of the expression of genes involved in lipogenesis and obesity in humans and animals.

PubMed

Delzenne, N; Ferré, P; Beylot, M; Daubioul, C; Declercq, B; Diraison, F; Dugail, I; Foufelle, F; Foretz, M; Mace, K; Reimer, R; Palmer, G; Rutter, G; Tavare, J; Van Loo, J; Vidal, H

2001-08-01

Dietary digestible carbohydrates are able to modulate lipogenesis, by modifying the expression of genes coding for key lipogenic enzymes, like fatty acid synthase. The overall objective of the Nutrigene project (FAIR-CT97-3011) was to study the efficiency of various carbohydrates to modulate the lipogenic capacity and relevant gene expression in rat and human species (control and obese subjects) and to understand the underlying molecular mechanisms involved in the regulation of lipogenic genes by carbohydrates. Key cellular mediators (namely SREBP-1c and 2, AMP activated protein kinase, cholesterol content) of the regulation of lipogenic gene expression by glucose and/or insulin were identified and constitute new putative targets in the development of plurimetabolic syndrome associated with obesity. In humans, hepatic lipogenesis and triglyceride synthesis, assessed in vivo by the use of stable isotopes, was promoted by a high-carbohydrate diet in non obese subjects, and in non alcoholic steatotic patients, but was not modified in the adipose tissue of obese subjects. Non digestible/fermentable carbohydrates, such as fructans, were shown to decrease hepatic lipogenesis in non obese rats, and to lessen hepatic steatosis and body weight in obese Zucker rats. If confirmed in obese humans, this would allow the development of functional food able to counteract the metabolic disturbances linked to obesity.

Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers.

PubMed

Aslan, Mehmet; Duzenli, Ufuk; Esen, Ramazan; Soyoral, Yasemin Usul

2017-10-01

The relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. Our present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). Obese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; p<0.001). Moreover, obese subjects have lower levels of TAC than in those in healthy subjects (p<0.001). In the Pearson's correlation analysis, enzyme activity of prolidase was positively related with TOS (p<0.001, r=0.529) and OSI (p<0.001, r=0.519) as well as BMI (p<0.001, r=0.692) and inversely related with TAC (p<0.05, r=-0.405) in obese subjects. Increased serum prolidase activity and decreased antioxidant levels are likely to be a results of increased of oxidative stress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Seasonal differences in melatonin concentrations and heart rates during sleep in obese subjects in Japan

NASA Astrophysics Data System (ADS)

Sato, Maki; Kanikowska, Dominika; Iwase, Satoshi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko; Sato, Motohiko; Sugenoya, Junichi

2013-09-01

During the past several decades, obesity has been increasing globally. In Japan, obesity is defined by a BMI of 25 kg/m2 or over; 28.6 % of men and 20.6 % of women are obese. Obese people have an increased incidence of developing cardiovascular, renal, and hormonal diseases and sleep disorders. Obese people also have shortened sleep durations. We investigated seasonal differences in melatonin concentrations, heart rates, and heart rate variability during sleep in obese subjects in Japan. Five obese (BMI, 32.0 ± 4.9 kg/m2) and five non-obese (BMI, 23.2 ± 2.9 kg/m2) men participated in this study in the summer and winter. Electrocardiograms were measured continuously overnight in a climatic chamber at 26 °C with a relative humidity of 50 %. Saliva samples for melatonin were collected at 2300 hours, 0200 hours, and 0600 hours. We found that melatonin concentrations during sleep in obese subjects were significantly lower than those in non-obese subjects in the winter. Heart rate during sleep in winter was significantly higher than that in summer in both obese and non-obese subjects. Heart rate variability was not significantly different in the summer and winter in both obese and non-obese subjects. Our results show that decreased nocturnal melatonin concentrations during winter in obese men may be related to higher heart rates, and this may suggest that obese men are at an increased risk of a cardiovascular incident during sleep, especially in the winter.

Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

PubMed Central

Henegar, Corneliu; Tordjman, Joan; Achard, Vincent; Lacasa, Danièle; Cremer, Isabelle; Guerre-Millo, Michèle; Poitou, Christine; Basdevant, Arnaud; Stich, Vladimir; Viguerie, Nathalie; Langin, Dominique; Bedossa, Pierre; Zucker, Jean-Daniel; Clement, Karine

2008-01-01

Background Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT). However, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear. Results Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components. Conclusion This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration associated with the development of obesity. PMID:18208606

Comparison of soft tissue artifact and its effects on knee kinematics between non-obese and obese subjects performing a squatting activity recorded using an exoskeleton.

PubMed

Clément, Julien; de Guise, Jaques A; Fuentes, Alexandre; Hagemeister, Nicola

2018-03-01

Rigid attachment systems are one of the methods used to compensate for soft tissue artifact (STA) inherent in joint motion analyses. The goal of this study was to quantify STA of an exoskeleton design to reduce STA at the knee, and to assess the accuracy of 3D knee kinematics recorded with the exoskeleton in non-obese and obese subjects during quasi-static weight-bearing squatting activity using biplane radiography. Nine non-obese and eight obese subjects were recruited. The exoskeleton was calibrated on each subject before they performed a quasistatic squatting activity in the EOS ® imaging system. 3D models of exoskeleton markers and knee bones were reconstructed from EOS ® radiographs; they served to quantify STA and to evaluate differences between the markers and bones knee kinematics during the squatting activity. The results showed that STA observed at the femur was larger in non-obese subjects than in obese subjects in frontal rotation (p = 0.004), axial rotation (p = 0.000), medio-lateral displacement (p = 0.000) and antero-posterior displacement (p = 0.019), while STA observed at the tibia was lower in non-obese subjects than in obese subjects for the three rotations (p < 0.05) and medio-lateral displacement (p = 0.015). Differences between the markers and bones knee kinematics increased with knee flexion and were similar in both groups, except for abduction-adduction: 4.9° for non-obese subjects against 2.3° for obese subjects (p = 0.011). This study demonstrated that STA at the femur and its impact on knee abduction-adduction using a specific exoskeleton were greater among non-obese subjects than obese subjects, which is encouraging for future biomechanical studies on pathologies such as osteoarthritis. Copyright © 2018 Elsevier B.V. All rights reserved.

Circulating Adipokines in Healthy versus Unhealthy Overweight and Obese Subjects

PubMed Central

Alfadda, Assim A.

2014-01-01

It is now well established that not all obese subjects are at increased risk of cardiometabolic complications; such patients are termed the metabolically healthy obese. Despite their higher-than-normal body fat mass, they are still insulin sensitive, with a favorable inflammatory and lipid profile and no signs of hypertension. It remains unclear which factors determine an individual's metabolic health. Adipose tissue is known to secrete multiple bioactive substances, called adipokines, that can contribute to the development of obesity-associated complications. The goal of this study was to determine whether the circulating adipokine profiles differs between metabolically healthy and metabolically unhealthy overweight and obese subjects, thereby obtaining data that could help to explain the link between obesity and its related cardiometabolic complications. We defined metabolic health in terms of several metabolic and inflammatory risk factors. The serum adiponectin levels were higher in the healthy group and showed a positive correlation with HDL cholesterol levels in the unhealthy group. There were no differences between the two groups in the levels of serum leptin, chemerin and orosomucoid. Accordingly, adiponectin might play a role in protecting against obesity-associated cardiometabolic derangements. More studies are needed to clarify the role of different chemerin isoforms in this system. PMID:24550983

Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

PubMed

Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

2001-12-01

Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

How to Estimate Fat Mass in Overweight and Obese Subjects

PubMed Central

Donini, Lorenzo Maria; Poggiogalle, Eleonora; del Balzo, Valeria; Lubrano, Carla; Faliva, Milena; Opizzi, Annalisa; Perna, Simone; Pinto, Alessandro; Rondanelli, Mariangela

2013-01-01

Background. The prevalence of overweight and obesity is increasing and represents a primary health concern. Body composition evaluation is rarely performed in overweight/obese subjects, and the diagnosis is almost always achieved just considering body mass index (BMI). In fact, whereas BMI can be considered an important tool in epidemiological surveys, different papers stated the limitations of the use of BMI in single individuals. Aim. To assess the determinants of body composition in overweight and obese subjects. Methods. In 103 overweight or obese subjects (74 women, aged 41.5 ± 10 years, and 29 men, aged 43.8 ± 8 years), a multidimensional evaluation was performed including the assessment of body composition using Dual Energy X-Ray Absorptiometry (DXA), anthropometry, bioimpedance analysis (BIA), and biochemical parameters (total cholesterol, triacylglycerol, HDL- and LDL-cholesterol, free fatty acids and glycerol, glucose, insulin, C-reactive protein, plasma acylated and unacylated ghrelin, adiponectin, and leptin serum levels). Results. BMI does not represent the main predictor of FM estimated by DXA; FM from BIA and hip circumference showed a better association with FM from DXA. Moreover, models omitting BMI explained a greater part of variance. These data are confirmed by the predictive value analysis where BMI showed a performance similar to a “coin flip.” PMID:23662101

WNT5A-JNK regulation of vascular insulin resistance in human obesity.

PubMed

Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

2016-12-01

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

WNT5A-JNK regulation of vascular insulin resistance in human obesity

PubMed Central

Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

2017-01-01

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m2) and five metabolically normal non-obese (BMI 26±2 kg/m2) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. PMID:27688298

Comparison of two physical activity questionnaires in obese subjects: the NUGENOB study.

PubMed

Tehard, Bertrand; Saris, Wim H M; Astrup, Arne; Martinez, J Alfredo; Taylor, Moira A; Barbe, Pierre; Richterova, Blanka; Guy-Grand, Bernard; Sørensen, Thorkild I A; Oppert, Jean-Michel

2005-09-01

Simple instruments are needed to assess habitual physical activity (PA) in obese subjects. In a multicenter European obesity project, we tested whether PA assessments by two questionnaires were correlated and similarly associated to selected obesity-related variables. A total of 757 obese subjects (75% female; age 37.1 [7.9] yr, BMI 35.5 [4.9] kg.m(-2), mean [SD]) completed the Baecke questionnaire (assessing work, sport, and nonsport leisure activity) and the short last 7-d version of the International Physical Activity Questionnaire (IPAQ; assessing vigorous, moderate-intensity, walking activity, and sitting). We assessed percent body fat (bioimpedance), waist circumference, and fasting plasma concentrations of glucose, insulin, leptin, and FFA. Insulin sensitivity was assessed by the HOMA index for insulin resistance (HOMAIR). Using the IPAQ, only about one third of men and women were classified as insufficiently active. Total habitual PA assessments by the Baecke and IPAQ were significantly related (Spearman rho = 0.51 in total sample, P < or = 0.0001, with adjustment for age, gender, and center). Using principal component analysis, we built two uncorrelated indices corresponding to general obesity (determined by high body fat and leptin) and abdominal obesity (determined by high waist circumference and HOMAIR). PA scores from both questionnaires were negatively related to general and abdominal obesity indices, except for abdominal obesity with the IPAQ in men. Total PA assessments by the two questionnaires were found to correlate significantly, and the general pattern of associations of PA with general obesity was similar for the two questionnaires. However, the IPAQ may capture less of the relationships between PA and abdominal obesity than the Baecke, especially in men. Reporting of habitual PA in obese subjects with the IPAQ warrants further evaluation against objective assessment methods.

Obese fathers lead to an altered metabolism and obesity in their children in adulthood: review of experimental and human studies.

PubMed

Ornellas, Fernanda; Carapeto, Priscila V; Mandarim-de-Lacerda, Carlos A; Aguila, Marcia B

To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication. Studies in humans and animals have established that paternal obesity impairs their hormones, metabolism, and sperm function, which can be transmitted to their offspring. In humans, paternal obesity results in insulin resistance/type 2 diabetes and increased levels of cortisol in umbilical cord blood, which increases the risk factors for cardiovascular disease. Notably, there is an association between body fat in parents and the prevalence of obesity in their daughters. In animals, paternal obesity led to offspring alterations on glucose-insulin homeostasis, hepatic lipogenesis, hypothalamus/feeding behavior, kidney of the offspring; it also impairs the reproductive potential of male offspring with sperm oxidative stress and mitochondrial dysfunction. An explanation for these observations (human and animal) is epigenetics, considered the primary tool for the transmission of phenotypes from the father to offspring, such as DNA methylation, histone modifications, and non-coding RNA. Paternal obesity can induce programmed phenotypes in offspring through epigenetics. Therefore, it can be considered a public health problem, affecting the children's future life. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Does fitness improve the cardiovascular risk profile in obese subjects?

PubMed

Halland, H; Lønnebakken, M T; Saeed, S; Midtbø, H; Cramariuc, D; Gerdts, E

2017-06-01

Good cardiorespiratory fitness has been suggested to reduce the risk of cardiovascular disease in obesity. We explored the association of fitness with the prevalences of major cardiovascular risk factor like hypertension (HT), diabetes and metabolic syndrome (MetS) in overweight and obese subjects. Clinical data from 491 participants in the FAT associated CardiOvasculaR dysfunction (FATCOR) study were analyzed. Physical fitness was assessed by ergospirometry, and subjects with at least good level of performance for age and sex were classified as fit. HT subtypes were identified from clinic and 24-h ambulatory blood pressure in combination. Diabetes was diagnosed by oral glucose tolerance test. MetS was defined by the American Heart Association and National Heart, Lung and Blood Institute criteria. The participants were on average 48 years old (60% women), and mean body mass index (BMI) was 32 kg/m 2 . 28% of study participants were classified as fit. Fitness was not associated with lower prevalences of HT or HT subtypes, diabetes, MetS or individual MetS components (all p > 0.05). In multivariable regression analysis, being fit was characterized by lower waist circumference, BMI < 30 kg/m 2 , non-smoking and a higher muscle mass (all p < 0.05). In the FATCOR population, fitness was not associated with a lower prevalence of major cardiovascular risk factors like HT, diabetes or MetS. Given the strong association of cardiovascular risk factor burden with risk of clinical cardiovascular disease, these findings challenge the notion that fitness alone is associated with lower risk of cardiovascular disease in obesity. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Human adenovirus-36 antibody status is associated with obesity in children.

PubMed

Atkinson, Richard L; Lee, Insil; Shin, Hye-Jung; He, Jia

2010-04-01

Human adenovirus-36 (Ad-36) is thought to induce obesity by a direct effect of the viral E4orf1 gene on lipogenic enzymes in host adipocytes. Ad-36 prevalence is 30% in obese adults, but prevalence has not been reported in childhood obesity. To determine the prevalence of Ad-36 infection in obese Korean children (age 14.8 +/- 1.9; range 8.3-6.3 years); correlation of infection with BMI z-score and other obesity measures. Blood was drawn at the annual school physical exam or clinic visit; Ad-36 status was determined by serum neutralization assay; and routine serum chemistry values. A total of 30% of subjects were positive (N = 25) for Ad-36; 70% were negative (N = 59). Significantly higher BMI z-scores (1.92 vs. 1.65, p < 0.01) and waist circumferences (96.3 vs. 90.7 cm, p = 0.05) were found in infected versus uninfected children. Cardiovascular risk factors were not significantly different. Ad-36 infection is common in obese Korean children and correlates highly with obesity. Ad-36 may have played a role in the obesity and Type 2 diabetes epidemic in children.

Neck Circumference in Overweight/Obese Subjects who Visited the Binjai Supermall in Indonesia

PubMed Central

Lindarto, Dharma; Shierly; Syafril, Santi

2016-01-01

BACKGROUND: Neck circumference (NC) is a simple screening measure for identifying overweight and obesity, it reflects upper-body fat distribution and central obesity. AIM: To determine whether a single measure of NC might be used to identify overweight/obesity. MATERIAL AND METHODS: An observational, analytical, cross-sectional study was done. The subjects consisted of all consecutive subjects who visited Binjai Supermall (North Sumatera Province, Indonesia) between 23rd and 29th September 2015 and agreed to participate in the study. NC, weight, height, body mass index (BMI), and waist circumference (WC) were measured. Overweight and obesity were defined as BMIs of 23.0–24.9 and ≥ 25 kg/m2, respectively. RESULTS: In total, 1554 subjects participated. Of these, 1238 (79.7%) were overweight/obese. NC correlated significantly with weight, height, BMI, and WC. Receiver operating characteristic (ROC) analysis showed that for all men and women, the area under the curve of overweight/obesity for NC was 0.83 and 0.79, respectively. The best NC cutoff points for males and females that indicated overweight/obesity were ≥ 37 cm (sensitivity, 78.3% and specificity, 75.5%) and ≥ 33.5 cm (sensitivity, 76.6% and specificity, 66.7%), respectively. CONCLUSION: The NC cutoffs that were identified may be useful for screening for overweight/obesity and related co-morbidities. PMID:27703549

Association between Subjective Obesity Status and Smoking Behavior among Normal-Weight Women

ERIC Educational Resources Information Center

Kim, Dae-Hwan

2018-01-01

Smoking and obesity are chief causes of mortality, morbidity, and medical expenditure. However, few studies have investigated the linkage between subjective obesity status and smoking behavior. This study examines whether females in a normal body mass index range who perceive themselves as obese are more likely to smoke than those who do not…

Bioelectrical impedance analysis (BIA) for sarcopenic obesity (SO) diagnosis in young female subjects

NASA Astrophysics Data System (ADS)

González-Correa, C. H.; Caicedo-Eraso, J. C.; S, Villada-Gomez J.

2013-04-01

Sarcopenia is defined as a loss of muscle mass depending of ageing and affecting physical function (definition A). A new definition considers excluding mass reduction criterion (definition B). Obesity is pandemic and occurs at all ages. Sarcopenic obesity (SO) implies both processes. The purpose of this study was to compare the results obtained after applying these 2 definitions in 66 aged 22 ± 2.8 years overweight or obese young college women. Percentage body fat (%BF) and skeletal mass index (SMI) were estimated by BIA, muscle function by handgrip strength test (HGS) and physical performance by Harvard step test (HST). There were 9.1% and 90.9% overweight or obese subjects. Twenty nine subjects (43.9%) had decreased HGS and 22 (33.3%) had impaired physical performance. One obese subject (1.5%) met the criteria for sarcopenic obesity by definition A and 9 (13.6%) by definition B. Although a linear regression (α <0.05) showed a very weak association between these variables (r2 = 0.094, 0.037 and 0.275 respectively) it was observed a tendency for HGS, HST and SMI deterioration when %BF increases. However, other confounding factors must be investigated. Probably as the population gets more obese, the problematic of SO will be found earlier in life.

Poor oral hygiene and gingivitis are associated with obesity and overweight status in paediatric subjects.

PubMed

Franchini, Roberto; Petri, Antonella; Migliario, Mario; Rimondini, Lia

2011-11-01

The association between obesity and periodontitis has been extensively investigated in adults but not in young people. Our aim is to evaluate whether overweight/obese paediatric patients have a greater chance of being affected by gingivitis than those of normal weight. Ninety-eight subjects ranging between 10 and 17 years of age were classified as obese/overweight or normal weight on the basis of body mass index. Auxological data, blood pressure, insulin resistance, psychological profile, oral hygiene habits, plaque and gingival indices were collected. Anthropometric measurements and blood pressure were significantly higher in overweight/obese subjects than in the normal-weight subjects (p<0001). The overweight/obese subjects showed a worse attitude towards oral hygiene. Two-way anova revealed a significant effect of obesity status (p<0001) on the gingival index. Logistic and linear regression analyses identified gingivitis as dependent on insulin resistance and bad oral hygiene rather than on the overweight/obese status simply defined. Negative psychological features related to physical and academic self-concept were also risk factors for gingivitis probably because they were related to a generic poor self-awareness. The gingivitis observed in overweight and obese young subjects is probably due to a combination of metabolic and inflammatory profiles and neglected attitude towards oral hygiene. © 2011 John Wiley & Sons A/S.

Genetic & epigenetic approach to human obesity

PubMed Central

Rao, K. Rajender; Lal, Nirupama; Giridharan, N.V.

2014-01-01

Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed. PMID:25579139

Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea

PubMed Central

Perrini, Sebastio; Quaranta, Vitaliano Nicola; Falcone, Vito Antonio; Kounaki, Stella; Ciavarella, Alessandro; Ficarella, Romina; Barbaro, Maria; Nigro, Pasquale; Carratù, Pierluigi; Natalicchio, Annalisa; Laviola, Luigi; Resta, Onofrio

2017-01-01

BACKGROUND. In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. METHODS. We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. RESULTS. At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFβ, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFβ, and VEGFα, were decreased only in the therapeutic c-PAP group. CONCLUSION. CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. FUNDING. Ministero dell’Università e della Ricerca and Progetti di Rilevante Interesse Nazionale. PMID:28878129

Reduced Adipose Tissue Oxygenation in Human Obesity

PubMed Central

Pasarica, Magdalena; Sereda, Olga R.; Redman, Leanne M.; Albarado, Diana C.; Hymel, David T.; Roan, Laura E.; Rood, Jennifer C.; Burk, David H.; Smith, Steven R.

2009-01-01

OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity. CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. PMID:19074987

Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence12

PubMed Central

2016-01-01

Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects. PMID:27422504

Assessment of atrial electromechanical delay by tissue Doppler echocardiography in obese subjects.

PubMed

Yagmur, Julide; Cansel, Mehmet; Acikgoz, Nusret; Ermis, Necip; Yagmur, Murat; Atas, Halil; Tasolar, Hakan; Karakus, Yasin; Pekdemir, Hasan; Ozdemir, Ramazan

2011-04-01

Our aim was to evaluate whether atrial electromechanical delay measured by tissue Doppler imaging (TDI), which is an early predictor of atrial fibrillation (AF) development, is prolonged in obese subjects. A total of 40 obese and 40 normal-weight subjects with normal coronary angiograms were included in this study. P-wave dispersion (PWD) was calculated on the 12-lead electrocardiogram (ECG). Systolic and diastolic left ventricular (LV) functions, inter- and intra-atrial electromechanical delay were measured by TDI and conventional echocardiography. Inter- and intra-atrial electromechanical delay were significantly longer in the obese subjects compared with the controls (44.08 ± 10.06 vs. 19.35 ± 5.94 ms and 23.63 ± 6.41 vs. 5.13 ± 2.67 ms, P < 0.0001 for both, respectively). PWD was higher in obese subjects (53.40 ± 5.49 vs. 35.95 ± 5.93 ms, P < 0.0001). Left atrial (LA) diameter, LA volume index and LV diastolic parameters were significantly different between the groups. Interatrial electromechanical delay was correlated with PWD (r = 0.409, P = 0.009), high-sensitivity C-reactive protein (hsCRP) levels (r = 0.588, P < 0.0001). Interatrial electromechanical delay was positively correlated with LA diameter, LA volume index, and LV diastolic function parameters consisting of mitral early wave (E) deceleration time (DT) and isovolumetric relaxation time (IVRT; r = 0.323, P = 0.042; r = 0.387, P = 0.014; r = 0.339, P = 0.033; r = 0.325, P = 0.041; respectively) and, negatively correlated with mitral early (E) to late (A) wave ratio (E/A) (r = -0.380, P = 0.016) and myocardial early-to-late diastolic wave ratio (E(m)/A(m)) (r = -0.326, P = 0.040). This study showed that atrial electromechanical delay is prolonged in obese subjects. Prolonged atrial electromechanical delay is due to provoked low-grade inflammation as well as LA enlargement and early LV diastolic dysfunction in obese subjects.

Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence.

PubMed

Harvie, Michelle N; Howell, Tony

2016-07-01

Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects. © 2016 American Society for Nutrition.

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.

Contributions of dysglycemia, obesity and insulin resistance to impaired endothelium-dependent vasodilation in humans

PubMed Central

Han, KA; Patel, Y; Lteif, AA; Chisholm, R; Mather, KJ

2011-01-01

Background Individual effects of hyperglycemia and obesity to impair vascular health are recognized. However, the relative contributions of dysglycemia versus other obesity-related traits to vascular dysfunction have not been systematically evaluated. Methods We undertook a cross-sectional evaluation of factors contributing to vascular function in 271 consecutive subjects, categorized as non-obese normal glucose tolerant (n=115), non-obese dysglycemic (n=32), obese normal glucose tolerant (n=57), obese dysglycemic (n=38), or type 2 diabetic (n=29). Vascular function was measured invasively as leg blood flow responses to methacholine chloride, an endothelium-dependent vasodilator. Categorical and continuous analyses were used to assess the contributions of hyperglycemia to vascular dysfunction. Results Even among normoglycemic subjects, obese subjects had impaired vascular function compared to non-obese subjects (p=0.004). Vascular function was also impaired in non-obese dysglycemic subjects (p=0.04 versus non-obese normoglycemic subjects), to a level comparable to normoglycemic obese subjects. Within obese subject groups, gradations of dysglycemia including the presence of diabetes were not associated with further worsening of these vascular responses beyond the effect of obesity alone (p=NS comparing all obese groups, p<0.001 versus lean normoglycemic subjects). In univariate and multivariable modeling analyses we found that effects of glycemia were less powerful than effects of insulin resistance and obesity on vascular dysfunction. Conclusions Dysglycemia contributes to impaired vascular function in non-obese subjects, but obesity and insulin resistance are more important determinants of vascular function in obese and diabetic subjects. PMID:21309061

PCSK1 Variants and Human Obesity.

PubMed

Ramos-Molina, B; Martin, M G; Lindberg, I

2016-01-01

PCSK1, encoding prohormone convertase 1/3 (PC1/3), was one of the first genes linked to monogenic early-onset obesity. PC1/3 is a protease involved in the biosynthetic processing of a variety of neuropeptides and prohormones in endocrine tissues. PC1/3 activity is essential for the activating cleavage of many peptide hormone precursors implicated in the regulation of food ingestion, glucose homeostasis, and energy homeostasis, for example, proopiomelanocortin, proinsulin, proglucagon, and proghrelin. A large number of genome-wide association studies in a variety of different populations have now firmly established a link between three PCSK1 polymorphisms frequent in the population and increased risk of obesity. Human subjects with PC1/3 deficiency, a rare autosomal-recessive disorder caused by the presence of loss-of-function mutations in both alleles, are obese and display a complex set of endocrinopathies. Increasing numbers of genetic diagnoses of infants with persistent diarrhea has recently led to the finding of many novel PCSK1 mutations. PCSK1-deficient infants experience severe intestinal malabsorption during the first years of life, requiring controlled nutrition; these children then become hyperphagic, with associated obesity. The biochemical characterization of novel loss-of-function PCSK1 mutations has resulted in the discovery of new pathological mechanisms affecting the cell biology of the endocrine cell beyond simple loss of enzyme activity, for example, dominant-negative effects of certain mutants on wild-type PC1/3 protein, and activation of the cellular unfolded protein response by endoplasmic reticulum-retained mutants. A better understanding of these molecular and cellular pathologies may illuminate possible treatments for the complex endocrinopathy of PCSK1 deficiency, including obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic fuel utilization and subclinical atherosclerosis in overweight/obese subjects.

PubMed

Montalcini, Tiziana; Gazzaruso, Carmine; Ferro, Yvelise; Migliaccio, Valeria; Rotundo, Stefania; Castagna, Alberto; Pujia, Arturo

2013-10-01

The utilization of different macronutrients is relevant for the risk of obesity, diabetes, or the appearing of vascular complications. The Respiratory Quotient (RQ) is a parameter measuring the fuel utilizations; in fact, it can indicate the fat stores utilization or lipogenesis activation. Aim of this study was to investigate the link between the RQ and the subclinical carotid atherosclerosis presence in overweight/obese subjects. 132 subjects with body mass index at least 25, at conventional diet, underwent an Indirect Calorimetry for the measurement of the Resting Metabolic Rate as well as the RQ and an evaluation of carotid arteries with ultrasound. Biochemical analyses were also performed. The mean age was 48 ± 12 years. There was a positive relation between carotid intima-media thickness and RQ (p = 0.010), with the high value in the subgroup with high RQ (p = 0.045 vs. group with low RQ). The RQ, an index of fuel utilization, is positively associated to subclinical carotid atherosclerosis in overweight/obese individuals.

[Urinary excretion of catecholamines in obese subjects and in diabetics (author's transl)].

PubMed

Giorgino, R; Nardelli, G M; Scardapane, R

1976-03-01

95 obese subjects, 40 diabetics and 22 normal controls were investigated. The weight of all obese subjects was at least 20% higher than the ideal weight. Catecholamine excretion was determined a few days after hospitalization to minimize the influence of environmental changes. Spectrofluorimetric estimation of adrenaline and noradrenaline in the urine was carried out according to the method of von Euler and Lihajko. Statistical analysis of the results showed a significant increase in both adrenaline and noradrenaline excretion in the group of obeses subjects compared with the diabetics. The increased catecholamine excretion may represent the response of the adrenal medulla to the stress of the disease. Such an increase may be responsible for perpheral insulin resistence and hence acts as a diabetogenic factor. The results obtained emphasize the influence of catecholamines on insulin responsiveness, possibly constituting a major contribution to the diabetic state.

Prevalence and Determinants of Metabolic Health in Subjects with Obesity in Chinese Population.

PubMed

Zheng, Ruizhi; Yang, Min; Bao, Yuqian; Li, Hong; Shan, Zhongyan; Zhang, Bo; Liu, Juan; Lv, Qinguo; Wu, Ou; Zhu, Yimin; Lai, Maode

2015-10-28

The study was to investigate the prevalence of metabolic health in subjects with obesity in the Chinese population and to identify the determinants related to metabolic abnormality in obese individuals. 5013 subjects were recruited from seven provincial capitals in China. The obesity and metabolic status were classified based on body mass index (BMI) and the number of abnormalities in common components of metabolic syndrome. 27.9% of individuals with obesity were metabolically healthy. The prevalence of the metabolically healthy obese (MHO) phenotype was significantly decreased with age in women (p trend < 0.001), but not significantly in men (p trend = 0.349). Central obesity (odds ratio [OR] = 4.07, 95% confidence interval [CI] = 1.93-8.59), longer sedentary time (OR = 1.97, 95%CI = 1.27-3.06), and with a family history of obesity related diseases (hypertension, diabetes, dyslipidemia) (OR = 1.85, 95%CI = 1.26-2.71) were significantly associated with having metabolic abnormality in obese individuals. Higher levels of physical activity and more fruit/vegetable intake had decreased ORs of 0.67 (95%CI = 0.45-0.98) and 0.44 (95%CI = 0.28-0.70), respectively. 27.9% of obese participants are in metabolic health. Central obesity, physical activity, sedentary time, fruits/vegetables intake and family history of diseases are the determinants associated with metabolic status in obesity.

[Beta-endorphin and obesity. Possible pathogenetic implications].

PubMed

Giugliano, D; Saccomanno, F; Quatraro, A; Ceriello, A; Torella, R

1990-01-01

Several experimental data have documented the ability of both opiates and opioid peptides to stimulate food intake. On the other hand, the plasma beta-endorphin levels found in obese patients are higher than those observed in normal-weight controls, which may have pathogenetic implications. We have investigated the responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin in formerly obese subjects who had obtained by dieting the normalization of body weight and in lean controls. The data show that: a) the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; b) formerly obese subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin.

The anti-obesity effects of green tea in human intervention and basic molecular studies.

PubMed

Huang, J; Wang, Y; Xie, Z; Zhou, Y; Zhang, Y; Wan, X

2014-10-01

Many researchers have reported that obesity is a major risk factor for diabetes, cardiovascular diseases, several forms of cancer (such as breast, colon and prostate), pulmonary, osteoarticular and metabolic diseases in the past decades. Recently, the hypolipidemic and anti-obesity effects of green tea in animals and humans have slowly become a hot topic in nutritional and food science research. This review will up-date the information of the anti-obesity effects of green tea in human intervention and animal studies. During recent years, an increasing number of clinical trials have confirmed the beneficial effects of green tea on obesity. However, the optimal dose has not yet been established owing to the very different results from studies with a similar design, which may be caused by differences in the extent of obesity, dietary intake, physical activity intensity, the strength of subjects' compliance to test instruction, the genetic background of populations, body composition and dietary habits. Therefore, further investigations on a larger scale and with longer periods of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of metabolic risk factors and to determine differences in beneficial effects among diverse populations. Moreover, data from laboratory studies have shown that green tea has important roles in fat metabolism by reducing food intake, interrupting lipid emulsification and absorption, suppressing adipogenesis and lipid synthesis and increasing energy expenditure via thermogenesis, fat oxidation and fecal lipid excretion. However, the exact molecular mechanisms remain elusive.

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions

PubMed Central

Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A.; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy

2010-01-01

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise. PMID:20739506

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

PubMed

Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy; Musi, Nicolas

2010-11-01

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

Human subjects research handbook: Protecting human research subjects. Second edition

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

NONE

1996-01-30

This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

Levels of lipocalin-2 in crevicular fluid and tear fluid in chronic periodontitis and obesity subjects.

PubMed

Pradeep, Avani Raju; Nagpal, Kanika; Karvekar, Shruti; Patnaik, Kaushik

2016-11-01

Lipocalin-2, a 25 kDa secretory glycoprotein, was first found in the neutrophilic granules of humans and in mouse kidney cells. It has been shown to have an important role in inflammation. The aim of this study was to determine the levels of lipocalin-2 in gingival crevicular fluid and tear fluid in patients with obesity and chronic periodontitis. A total of 40 subjects in the age group 25-40 years were divided into four groups based on probing depth, gingival index, clinical attachment level, body mass index, and radiographic evidence of bone loss. The groups were: nonobese healthy group; obese healthy group; nonobese chronic periodontitis group; obese chronic periodontitis group Gingival crevicular fluid and tear fluid samples were collected on the subsequent day. There was an increase in lipocalin-2 levels from group 1 to group 4 (with the nonobese healthy group showing the least levels and obese chronic periodontitis group showing the highest levels) in both gingival crevicular fluid and tear fluid. Lipocalin-2 may be an important inflammatory marker that may help link obesity and chronic periodontitis. © 2015 Wiley Publishing Asia Pty Ltd.

Mapping and annotating obesity-related genes in pig and human genomes.

PubMed

Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

2014-01-01

Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

Preoperative gender differences in pulmonary gas exchange in morbidly obese subjects.

PubMed

Zavorsky, Gerald S; Christou, Nicolas V; Kim, Do Jun; Carli, Franco; Mayo, Nancy E

2008-12-01

Morbidly obese men may have poorer pulmonary gas exchange compared to morbidly obese women (see Zavorsky et al., Chest 131:362-367, 2007). The purpose was to compare pulmonary gas exchange in morbidly obese men and women at rest and throughout exercise. Twenty-five women (age=38+/-10 years, 164+/-7 cm, body mass index or BMI = 51+/-7 kg/m(2), peak oxygen consumption or VO(2peak)=2.0+/-0.4 l/min) and 17 men (age=43+/-9 years, 178+/-7 cm, BMI=50+/-10 kg/m(2), VO(2peak)=2.6+/-0.8 l/min) were recruited to perform a graded exercise test on a cycle ergometer with temperature-corrected arterial blood-gas samples taken at rest and every minute of exercise, including peak exercise. At rest, women were 98% predicted for pulmonary diffusion compared to 88% predicted in men. At rest, women had better pulmonary gas exchange compared to the men which was related to women having a lower waist-to-hip ratio (WHR; p<0.01). Only 20% of the subjects had an excessive alveolar-to-arterial oxygen partial pressure difference (>or=25 mmHg) at peak exercise, but 75% of the subjects showed inadequate compensatory hyperventilation at peak exercise (arterial carbon dioxide pressure >35 mmHg), and both were not different between genders. At rest, morbidly obese men have poorer pulmonary gas exchange and pulmonary diffusion compared to morbidly obese women. The better gas exchange in women is related to the lower WHR in the women. During exercise, few subjects showed disturbances in pulmonary gas exchange despite demonstrating poor compensatory hyperventilation at peak exercise.

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

PubMed

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

2016-09-01

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

Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults

USDA-ARS?s Scientific Manuscript database

Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits have shown health benefits in human and animal studies. In a double-blind, randomized, crossover study, 10 overweight/obese human subjects were fed pur...

Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects.

PubMed

Maraninchi, Marie; Padilla, Nadège; Béliard, Sophie; Berthet, Bruno; Nogueira, Juan-Patricio; Dupont-Roussel, Jeanine; Mancini, Julien; Bégu-Le Corroller, Audrey; Dubois, Noémie; Grangeot, Rachel; Mattei, Catherine; Monclar, Marion; Calabrese, Anastasia; Guérin, Carole; Desmarchelier, Charles; Nicolay, Alain; Xiao, Changting; Borel, Patrick; Lewis, Gary F; Valéro, René

Elevated apolipoprotein C-III (apoC-III) has been postulated to contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL) metabolism. Bariatric surgery is associated with improvements of several obesity-associated metabolic abnormalities, including a reduction in plasma triglycerides (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C). We investigated the specific effect of bariatric surgery on apoC-III concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile parameters evolution. A total of 132 obese subjects undergoing bariatric surgery, gastric bypass (n = 61) or sleeve gastrectomy (n = 71), were studied 1 month before surgery and 6 and 12 months after surgery. Plasma apoC-III, non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after surgery and strongly associated with reduction in plasma TG. This decrease was accompanied by a redistribution of apoC-III from TRL to HDL fractions. In multivariate analysis, plasma apoC-III was the strongest predictor of TG reduction after surgery, and the increase of HDL-C was positively associated with plasma adiponectin and negatively with body mass index. Marked reduction of apoC-III and changes in its distribution between TRL and HDL consistent with a better lipid profile are achieved in obese patients after bariatric surgery. These apoC-III beneficial modifications may have implications in dyslipidemia improvement and contribute to cardiovascular risk reduction after surgery. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

IRX3 Promotes the Browning of White Adipocytes and Its Rare Variants are Associated with Human Obesity Risk.

PubMed

Zou, Yaoyu; Lu, Peng; Shi, Juan; Liu, Wen; Yang, Minglan; Zhao, Shaoqian; Chen, Na; Chen, Maopei; Sun, Yingkai; Gao, Aibo; Chen, Qingbo; Zhang, Zhiguo; Ma, Qinyun; Ning, Tinglu; Ying, Xiayang; Jin, Jiabin; Deng, Xiaxing; Shen, Baiyong; Zhang, Yifei; Yuan, Bo; Kauderer, Sophie; Liu, Simin; Hong, Jie; Liu, Ruixin; Ning, Guang; Wang, Weiqing; Gu, Weiqiong; Wang, Jiqiu

2017-10-01

IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity. IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3's effects on UCP1 transcriptional activity. Moreover, genetic analysis of IRX3 was performed in 861 young obese subjects and 916 controls. IRX3 expression was induced in the browning process and was positively correlated with the browning markers. IRX3 knockdown remarkably inhibited UCP1 expression in induced mouse and human beige adipocytes, and also repressed the uncoupled oxygen consumption rate. Further, IRX3 directly bound to UCP1 promoter and increased its transcriptional activity. Moreover, 17 rare heterozygous missense/frameshift IRX3 variants were identified, with a significant enrichment in obese subjects (P=0.038, OR=2.27; 95% CI, 1.02-5.05). IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of obese and lean Zucker rat sera on human and rat prostate cancer cells: implications in obesity-related prostate tumor biology.

PubMed

Lamarre, Neil S; Ruggieri, Michael R; Braverman, Alan S; Gerstein, Matthew I; Mydlo, Jack H

2007-01-01

Several reports have demonstrated the effects of obesity on prostate cancer. Also several reports have linked expression of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (FGF-2) to prostate cancer aggressiveness. The objective of this study was to determine whether a difference exists between lean and obese Zucker rat sera on proliferation prostate cancer cell lines, as well as to examine the differences in FGF-2 and VEGF concentrations. Ten-week-old female obese and lean Zucker rat sera were subjected to charcoal stripping and tested for the proliferation of human LNCaP and rat AT3B-1 prostate cancer cells. An acetonitrile extract of the charcoal used to strip the sera was also tested for mitogenicity. VEGF and FGF-2 concentrations were determined by enzyme-linked immunosorbent assay. Both unstripped and charcoal-stripped obese rat sera had a greater mitogenic effect than did the lean sera on the LNCaP cell line. Charcoal stripping of both obese and lean sera reduced the mitogenic effect on the AT3B-1 cell line. The acetonitrile extract of the charcoal used to strip the sera was unable to recover this proliferative effect. The concentration of VEGF was greater in the obese serum than in the lean serum, and charcoal stripping reduced the concentrations of both FGF-2 and VEGF. The finding of greater VEGF in obese rat sera, as well as greater mitogenic responses on human prostate cancer cells in vitro, suggests this as one of the many possible mechanisms involved in obesity-related prostate cancer biology.

[Exploratory population study of overweight and obese subjects' perceptions: Searching for improved management practices].

PubMed

Crutze, C; Pétré, B; Dardenne, N; Donneau, A-F; Streel, S; Albert, A; Scheen, A; Husson, E; Guillaume, M

2017-06-01

Overweight and obesity are major public health problems of growing concern. Few studies have investigated the representations and perceptions of subjects with overweight and obesity, especially in the general population, as compared to people in a medical weight loss process. The objective of this study was to fill this gap by enabling participants to express their feelings and experience about their overweight, and to assess the extent of the body mass index (BMI) as a determinant of these perceptions. A total of 4155 persons participated in an exploratory study conducted in Wallonia (Belgium). Data were collected by means of a web-based questionnaire. This study investigated the following parameters: sociodemographic and anthropometric factors, perceived health, quality of life, diet perception, enrolment in a weight loss process and weight loss target. The influence of BMI was considered, on one hand, looking at how the above variables evolve according to BMI category, secondly, as a mediation factor in the relationship between socioeconomic level and these same variables. A large majority (87.5%) of subjects were overweight (32.2%) or obese (obese class I 29.9%, class II 14.8%, class III 10.6%). Perceived health was found to deteriorate with the BMI (P<0.0001); obese class III had a 5.9-fold risk to present bad perceived health compared to subjects with normal weight. The physical and psychological quality of life reported by the subjects decreased significantly with the BMI (P<0.0001) particularly for the physical quality of life. The percentage of poor diet perception (frustration, weight gain, aggressiveness, inefficacy and impossibility) as well as the weight loss targeted by the subjects increased with the BMI. Between overweight subjects and obese class III subjects, weight loss target increased from 13% to 34% of the initial weight. The majority of subjects judged that diet represents "aggressiveness", "weight gain" and "impossibility". A partial

Decreased Bone Mineral Density in Prader-Willi Syndrome: Comparison With Obese Subjects

PubMed Central

Butler, Merlin G.; Haber, Lawrence; Mernaugh, Ray; Carlson, Michael G.; Price, Ron; Feurer, Irene D.

2016-01-01

Bone density, anthropometric data, and markers of bone turnover were collected on 21 subjects diagnosed with Prader-Willi syndrome (PWS) and compared with 9 subjects with obesity of unknown cause. In addition, urinary N-telopeptide levels were obtained in all subjects. N-telopeptides are the peptide fragments of type I collagen, the major bone matrix material. During periods of active bone degradation or high bone turnover, high levels of N-telopeptides are excreted in the urine. However, no significant difference was detected in the urinary N-telopeptide levels when corrected for creatinine excretion (raw or transformed data) between our subjects with obesity or PWS and the observed effect size of the between-group difference was small. Although N-telopeptide levels were higher but not significantly different in the subjects with PWS compared with obese controls, the subjects with PWS had significantly decreased total bone and spine mineral density and total bone mineral content (all P < 0.001). No differences in N- telopeptide levels or bone mineral density were observed between subjects with PWS and chromosome 15q deletion or maternal disomy. Thus, decreased bone mineral density in subjects with PWS may relate to the lack of depositing bone mineral during growth when bones are becoming more dense (e.g., during adolescence), possibly because of decreased production of sex or growth hormones and/or long-standing hypotonia. It may not be caused by loss, or active degradation, of bone matrix measurable by the methods described in this study further supporting the possible need for hormone therapy during adolescence. PMID:11745993

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects.

PubMed

Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T; Molina-Carrion, Marjorie; DeFronzo, Ralph A; Sakamoto, Kei; Musi, Nicolas

2012-07-01

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of Vo(2max)). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K(m) for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser(641), Ser(645), and Ser(645,649,653,657)), and phosphorylation of these sites remained decreased after 3.5 h; Ser⁷ phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K(m) for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

Molecular genetics of human obesity: A comprehensive review.

PubMed

Singh, Rajan Kumar; Kumar, Permendra; Mahalingam, Kulandaivelu

2017-02-01

Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population.

PubMed

Rong, Rong; Tao, Ya-Xiong; Cheung, Bernard M Y; Xu, Aimin; Cheung, Grace C N; Lam, Karen S L

2006-08-01

Mutations in the melanocortin-4 receptor gene (MC4R) are the most common monogenic form of human obesity. However, the contribution of MC4R mutations to obesity in Chinese has not been investigated. We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequences of the novel variants identified. We screened for MC4R mutations in 227 obese [body mass index (BMI) 35.29 +/- 5.75 kg/m2] and 100 lean (BMI 21.57 +/- 0.29 kg/m2) southern Chinese subjects using PCR-direct sequencing. In vitro functional studies, including cell surface expression, ligand binding, and cyclic adenosine monophosphate (cAMP) accumulation, were performed to examine the functional properties of three novel missense mutations. Apart from two previously reported polymorphisms, V103I and -176 A > C, three novel missense heterozygous variants (Y35C, C40R and M218T) were identified. The polymorphisms -176 A > C and Y35C were detected in both obese and normal subjects with similar frequency. C40R was identified only in an obese subject. Pedigree analysis revealed M218T carriers in both lean and obese subjects. The prevalence of V103I carriers in normal-weight controls was significantly higher than that in obese subjects (5.3%vs. 1.3%, P < 0.05). In vitro functional studies showed that all three novel missense variants have normal functions. Two known polymorphisms and three novel variants of the MC4R were identified. No overt functional defects were observed for the three novel MC4R variants, suggesting that they might not be the cause of obesity in variant carriers.

Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.

PubMed

Wofford, M R; Anderson, D C; Brown, C A; Jones, D W; Miller, M E; Hall, J E

2001-07-01

The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and nine lean patients with a BMI < or =25 kg/m2 (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the alpha-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02) and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/-1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

The CIDEA gene V115F polymorphism is associated with obesity in Swedish subjects.

PubMed

Dahlman, Ingrid; Kaaman, Maria; Jiao, Hong; Kere, Juha; Laakso, Markku; Arner, Peter

2005-10-01

The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesity in two independent Swedish samples; the first comprised 981 women and the second 582 men. Both samples display a large variation in BMI. The only detected coding polymorphism encodes an exon 4 V115F amino acid substitution, which is associated with BMI in both sexes (P = 0.021 for women, P = 0.023 for men, and P = 0.0015 for joint analysis). These results support a role for CIDEA alleles in human obesity. CIDEA-deficient mice display higher metabolic rate, and the gene cross-talks with tumor necrosis factor-alpha (TNF-alpha) in fat cells. We hypothesize that CIDEA alleles regulate human obesity through impact on basal metabolic rate and adipocyte TNF-alpha signaling.

Association Between Subjective Obesity Status and Smoking Behavior Among Normal-Weight Women.

PubMed

Kim, Dae-Hwan

2018-06-01

Smoking and obesity are chief causes of mortality, morbidity, and medical expenditure. However, few studies have investigated the linkage between subjective obesity status and smoking behavior. This study examines whether females in a normal body mass index range who perceive themselves as obese are more likely to smoke than those who do not perceive themselves as obese. Stratifying by age-group, I employed the propensity score matching analysis to control for selection bias. Although body mass index is lower for younger females aged 20 to 39, they are more likely than elder females to consider themselves as obese. Based on a logistic regression, my findings show that younger females who perceive themselves as obese are 21.2% more likely to smoke than females who do not perceive themselves as obese. The positive relationship between perceived obesity status and smoking behavior is also found in the propensity score matching analysis. However, the disparity in smoking prevalence is not detected between elder females who perceive themselves as obese and those who do not. Public education that fosters accurate perception of body shape is imperative in inducing healthy lifestyles and improving social welfare.

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

PubMed Central

Pierce, Joseph R.; Maples, Jill M.

2015-01-01

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

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects

PubMed Central

Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T.; Molina-Carrion, Marjorie; DeFronzo, Ralph A.; Sakamoto, Kei

2012-01-01

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇o2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS Km for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50–70% (Ser641, Ser645, and Ser645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased Km for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects. PMID:22510711

Subjective Well-Being in Obese Individuals: The Multiple Roles of Exercise

ERIC Educational Resources Information Center

Berger, Bonnie G.

2004-01-01

This paper focuses on the tangled web of obesity and exercise as it relates to subjective well-being. Many overweight individuals have low levels of subjective well-being as a reflection of "anti-fat" biases and sociocultural considerations. Since exercise helps balance the energy intake-output equation and is associated with mood benefits,…

Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects.

PubMed

Haufe, Sven; Engeli, Stefan; Kast, Petra; Böhnke, Jana; Utz, Wolfgang; Haas, Verena; Hermsdorf, Mario; Mähler, Anja; Wiesner, Susanne; Birkenfeld, Andreas L; Sell, Henrike; Otto, Christoph; Mehling, Heidrun; Luft, Friedrich C; Eckel, Juergen; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens

2011-05-01

Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. Copyright © 2011 American Association for the Study of Liver Diseases.

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Thanos, Panayotis K.; Logan, Jean; Alexoff, David; Ding, Yu-Shin; Wong, Christopher; Ma, Yeming; Pradhan, Kith

2009-01-01

Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI>40 kg/m2) and compared it to that in twelve non-obese controls. PET was used with [11C]raclopride to assess D2 receptors and with [18F] FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food. PMID:18598772

Prevalence of diabetes, obesity, and metabolic syndrome in subjects with and without schizophrenia (CURES-104).

PubMed

Subashini, R; Deepa, M; Padmavati, R; Thara, R; Mohan, V

2011-01-01

There are some reports that diabetes and metabolic syndrome (MS) are more prevalent among schizophrenia patients. However, there are very few studies in India which have estimated the prevalence of diabetes and MS in schizophrenia patients. The aim of this study was to determine the prevalence of diabetes, obesity, and MS in subjects with and without schizophrenia. This case control study comprised of "cases" i.e. subjects with schizophrenia recruited from a schizophrenia centre at Chennai and "controls" i.e. healthy age- and gender-matched subjects without psychiatric illness selected from an ongoing epidemiological study in Chennai in a 1:4 ratio of cases: Controls. Fasting plasma glucose and serum lipids were estimated for all subjects. Anthropometric measures including height, weight, and waist circumference were assessed. Diabetes and impaired fasting glucose (IFG) were defined using American Diabetes Association criteria. One-way ANOVA or student's "t" test was used to compare continuous variables and Chi-square test to compare proportion between two groups. The study group comprised of 655 subjects, 131 with schizophrenia and a control group of 524 subjects without schizophrenia. The prevalence of the diabetes, IFG, abdominal obesity and MS were significantly higher among subjects with schizophrenia compared to those without schizophrenia-diabetes (15.3% vs. 7.3%, P=0.003), IFG (31.3% vs. 8.6%, P<0.001), abdominal obesity (59.2% vs. 44.7%, P<0.001), and MS (34.4% vs. 24%, P=0.014). In subjects with schizophrenia, the prevalence of diabetes, IFG, abdominal obesity, and MS is significantly higher than in those without schizophrenia.

Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

PubMed

Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

2018-04-01

Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity.

PubMed

Knop, Filip K; Aaboe, K; Vilsbøll, T; Vølund, A; Holst, J J; Krarup, T; Madsbad, S

2012-06-01

People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses. Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m(2)]; (ii) Eight obese subjects with NGT [BMI: 33 (35-38) kg/m(2)]; (iii) Eight lean patients with T2DM [BMI: 24 (22-25) kg/m(2)]; and (iv) Eight lean healthy subjects [BMI: 23 (20-25) kg/m(2)]. The incretin effect was significantly (p < 0.05) reduced in patients with T2DM {obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p < 0.05). Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects. Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin-resistant state have NGT. © 2011 Blackwell Publishing Ltd.

The Neuropathology of Obesity: Insights from Human Disease

PubMed Central

Lee, Edward B.; Mattson, Mark P.

2013-01-01

Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand’s syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer’s disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans

PubMed Central

Hulver, Matthew W.; Berggren, Jason R.; Carper, Michael J.; Miyazaki, Makoto; Ntambi, James M.; Hoffman, Eric P.; Thyfault, John P.; Stevens, Robert; Dohm, G. Lynis; Houmard, Joseph A.; Muoio, Deborah M.

2014-01-01

Summary Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. PMID:16213227

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

PubMed

Hulver, Matthew W; Berggren, Jason R; Carper, Michael J; Miyazaki, Makoto; Ntambi, James M; Hoffman, Eric P; Thyfault, John P; Stevens, Robert; Dohm, G Lynis; Houmard, Joseph A; Muoio, Deborah M

2005-10-01

Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

Obesity genetics in mouse and human: back and forth, and back again

PubMed Central

Yazdi, Fereshteh T.; Clee, Susanne M.

2015-01-01

Obesity is a major public health concern. This condition results from a constant and complex interplay between predisposing genes and environmental stimuli. Current attempts to manage obesity have been moderately effective and a better understanding of the etiology of obesity is required for the development of more successful and personalized prevention and treatment options. To that effect, mouse models have been an essential tool in expanding our understanding of obesity, due to the availability of their complete genome sequence, genetically identified and defined strains, various tools for genetic manipulation and the accessibility of target tissues for obesity that are not easily attainable from humans. Our knowledge of monogenic obesity in humans greatly benefited from the mouse obesity genetics field. Genes underlying highly penetrant forms of monogenic obesity are part of the leptin-melanocortin pathway in the hypothalamus. Recently, hypothesis-generating genome-wide association studies for polygenic obesity traits in humans have led to the identification of 119 common gene variants with modest effect, most of them having an unknown function. These discoveries have led to novel animal models and have illuminated new biologic pathways. Integrated mouse-human genetic approaches have firmly established new obesity candidate genes. Innovative strategies recently developed by scientists are described in this review to accelerate the identification of causal genes and deepen our understanding of obesity etiology. An exhaustive dissection of the molecular roots of obesity may ultimately help to tackle the growing obesity epidemic worldwide. PMID:25825681

Approach to testing growth hormone (GH) secretion in obese subjects.

PubMed

Popovic, Vera

2013-05-01

Identification of adults with GH deficiency (GHD) is challenging because clinical features of adult GHD are not distinctive and because clinical suspicion must be confirmed by biochemical tests. Adults are selected for testing for adult GHD if they have a high pretest probability of GHD, ie, if they have hypothalamic-pituitary disease, if they have received cranial irradiation or central nervous system tumor treatment, or if they survived traumatic brain injury or subarachnoid hemorrhage. Testing should only be carried out if a decision has already been made that if deficiency is found it will be treated. There are many pharmacological GH stimulation tests for the diagnosis of GHD; however, none fulfill the requirements for an ideal test having high discriminatory power; being reproducible, safe, convenient, and economical; and not being dependent on confounding factors such as age, gender, nutritional status, and in particular obesity. In obesity, GH secretion is reduced, GH clearance is enhanced, and stimulated GH secretion is reduced, causing a false-positive result. This functional hyposomatotropism in obesity is fully reversed by weight loss. In conclusion, GH stimulation tests should be avoided in obese subjects with very low pretest probability.

Obesity and Aging in Humans and Nonhuman Primates: A Mini-Review.

PubMed

Vaughan, Kelli L; Mattison, Julie A

2016-01-01

The prevalence of obesity in the US is increasing exponentially across gender, age and ethnic groups. Obesity and a long-term hypercaloric diet result in what appears to be accelerated aging, often leading to a multi-systemic deterioration known as the metabolic syndrome. Due to their physiological similarity to humans as well as comparable rates of spontaneous obesity and diabetes mellitus, nonhuman primates provide a useful translational model for the human condition. They allow for an in vivo study of disease progression, interaction of comorbidities, and novel interventions. However, defining obesity in aged humans and nonhuman primates is difficult as the physiological changes that occur with aging are not accounted for using our current systems (BMI - body mass index and BCS - body condition score). Nonetheless, nonhuman primate studies have greatly contributed to our understanding of obesity and metabolic dysfunction and should continue to play a large role in translational research. Here, methods for defining obesity and metabolic syndrome in humans and nonhuman primates are described along with the prevalence and effects of these conditions. © 2016 S. Karger AG, Basel.

Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

PubMed Central

Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

2018-01-01

Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

Fat content in individual muscle fibers of lean and obese subjects.

PubMed

Malenfant, P; Joanisse, D R; Thériault, R; Goodpaster, B H; Kelley, D E; Simoneau, J A

2001-09-01

To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity. Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals. Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and 14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable proportions of men and women. Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined. The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean, P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%; P<0.05). The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

No association of apolipoprotein B gene polymorphism and blood lipids in obese Egyptian subjects.

PubMed

Bogari, Neda M; Abdel-Latif, Azza M; Hassan, Maha A; Ramadan, Abeer; Fawzy, Ahmed

2015-03-18

Several environmental and genetic factors are associated with high levels of lipids in obese patients. Apolipoprotein B (ApoB) is the major protein component of low-density lipoproteins (LDL), very-low density lipoproteins (VLDL) and chylomicrons and plays a central role in lipid metabolism. Several apoB restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels and obesity. To date, no data are available on the relationship between XbaI polymorphism and lipid levels in Egyptian populations. Following clinical profiling, 178 obese (body mass index [BMI] >25 kg/m(2)) and 178 age-matched non-obese (BMI ≤ 25 kg/m(2)) subjects were included in this case-control study. All samples were analysed for total cholesterol, triglycerides and HDL-cholesterol. Genetic analysis of apoB XbaI (X) was performed using Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). The aim of this study was to assess the association of apoB XbaI gene polymorphism (X) and lipid profiles in obese and non-obese Egyptian populations. Obese subjects demonstrated significantly higher values of waist-to-hip ratio, blood pressure, and total lipid. However, in our sample we did not find significant differences in apoB XbaI gene polymorphism (X) genotype or allele frequencies. Moreover, none of the studied lipid parameters showed any association with the gene polymorphism. This study reveals no significant association of apoB XbaI gene polymorphism (X) with obesity or lipid profiles in an Egyptian population.

Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.

PubMed

Hendricks, Audrey E; Bochukova, Elena G; Marenne, Gaëlle; Keogh, Julia M; Atanassova, Neli; Bounds, Rebecca; Wheeler, Eleanor; Mistry, Vanisha; Henning, Elana; Körner, Antje; Muddyman, Dawn; McCarthy, Shane; Hinney, Anke; Hebebrand, Johannes; Scott, Robert A; Langenberg, Claudia; Wareham, Nick J; Surendran, Praveen; Howson, Joanna M; Butterworth, Adam S; Danesh, John; Nordestgaard, Børge G; Nielsen, Sune F; Afzal, Shoaib; Papadia, Sofia; Ashford, Sofie; Garg, Sumedha; Millhauser, Glenn L; Palomino, Rafael I; Kwasniewska, Alexandra; Tachmazidou, Ioanna; O'Rahilly, Stephen; Zeggini, Eleftheria; Barroso, Inês; Farooqi, I Sadaf

2017-06-29

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10 -3 ), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.

Food and drug reward: overlapping circuits in human obesity and addiction.

PubMed

Volkow, N D; Wang, G J; Fowler, J S; Tomasi, D; Baler, R

2012-01-01

Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects-partly mediated by dopamine increases in the limbic system-that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioural inhibition), stress reactivity, and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that shed light on the role of dopamine in drug addiction and in obesity, and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.

Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit

PubMed Central

Tran, Lee; Hanavan, Paul D.; Campbell, Latoya E.; De Filippis, Elena; Lake, Douglas F.; Coletta, Dawn K.; Roust, Lori R.; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

2016-01-01

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish

Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit.

PubMed

Tran, Lee; Hanavan, Paul D; Campbell, Latoya E; De Filippis, Elena; Lake, Douglas F; Coletta, Dawn K; Roust, Lori R; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

2016-01-01

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = - 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish

Effects of bariatric surgery on disability pension in Swedish obese subjects.

PubMed

Gripeteg, L; Lindroos, A K; Peltonen, M; Sjöström, L; Narbro, K

2012-03-01

Prospective controlled data on the long-term effects of bariatric surgery on disability pension are not available. This study prospectively compare disability pension in surgically and conventionally treated obese men and women. The Swedish obese subjects study started in 1987 and involved 2010 obese patients who had bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. Outcomes of this report were: (i) incidence of disability pension from study inclusion to 31 December 2006 in all subjects, and, (ii) number of disability pension days over 10 years in a subgroup of individuals (N=2901) followed for at least 10 years where partial pensions were recalculated to full number of days per year. Objective information on granted disability pension was obtained from the Swedish Social Insurance Agency and disability pension follow-up rate was 99.9%. In men, the unadjusted incidence of disability pension did not differ between the surgery and control groups (N=156 in both groups). When adjusting for baseline confounders in men, a reduced risk of disability pension was suggested in the surgery group (hazard ratio 0.79, 95% confidence interval 0.62-1.00; P=0.05). Furthermore, the adjusted average number of disability pension days was lower in the surgery group, 609 versus 734 days (P=0.01). In women, bariatric surgery was not associated with significant effects on incidence or number of days of disability pension. Bariatric surgery may be associated with favourable effects on disability pension for up to 19 years in men whereas neither favourable nor unfavourable effects could be detected in women.

Contribution of daily and seasonal biorhythms to obesity in humans

NASA Astrophysics Data System (ADS)

Kanikowska, Dominika; Sato, Maki; Witowski, Janusz

2015-04-01

While the significance of obesity as a serious health problem is well recognized, little is known about whether and how biometerological factors and biorhythms causally contribute to obesity. Obesity is often associated with altered seasonal and daily rhythmicity in food intake, metabolism and adipose tissue function. Environmental stimuli affect both seasonal and daily rhythms, and the latter are under additional control of internal molecular oscillators, or body clocks. Modifications of clock genes in animals and changes to normal daily rhythms in humans (as in shift work and sleep deprivation) result in metabolic dysregulation that favours weight gain. Here, we briefly review the potential links between biorhythms and obesity in humans.

Hepatic iron content is independently associated with serum hepcidin levels in subjects with obesity.

PubMed

Moreno-Navarrete, José María; Moreno, María; Puig, Josep; Blasco, Gerard; Ortega, Francisco; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel

2017-10-01

Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed. Serum hepcidin, ferritin and hepatic iron content (HIC) were significantly increased in participants with obesity. Age- and gender-adjusted serum hepcidin was positively correlated with BMI, hsCRP, ferritin and HIC. In addition, age- and gender-adjusted serum hepcidin was positively correlated with ferritin and HIC in both non-obese and obese participants. In multivariate regression analysis, hepatic iron content (p < 0.01) and serum ferritin (p < 0.001) contributed independently to circulating hepcidin concentration variation after controlling for age, gender, BMI and hsCRP. Diet intervention-induced weight loss led to decreased serum hepcidin (p = 0.01), serum ferritin concentration (p = 0.01) and HIC (p = 0.002). Of note, the percent change of serum hepcidin strongly correlated with the percent change of serum ferritin (r = 0.69, p = 0.01) and HIC (r = 0.61, p = 0.03) even after controlling for age and gender. Serum hepcidin is a reliable marker of the hepatic iron content in subjects with obesity. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Increasing plasma free fatty acids in healthy subjects induces aortic distensibility changes seen in obesity.

PubMed

Rider, Oliver J; Holloway, Cameron J; Emmanuel, Yaso; Bloch, Edward; Clarke, Kieran; Neubauer, Stefan

2012-05-01

Elevated free fatty acid (FFA) levels are known to impair aortic elastic function. In obesity, FFA levels are elevated and aortic distensibility (AD) reduced in a pattern that predominantly affects the distal aorta. Despite this, the role of FFAs in obesity-related aortic stiffness remains unclear. Using vascular MRI, we aimed to determine if (1) FFA level correlated with AD in obesity; and (2) whether elevating FFA acutely and subacutely in normal-weight subjects reproduced the distal pattern of AD change in obesity. To do this, regional AD was recorded in 35 normal-weight and 70 obese subjects and then correlated with FFA levels. When compared with normal weight, obesity was associated with reduced AD in a pattern predominantly affecting the distal aorta (ascending aorta by -22%, proximal descending aorta by -25%, and abdominal aorta by -35%; P<0.001). After controlling for age, blood pressure, and body mass index, FFA levels remained negatively correlated with abdominal AD (r=-0.43, P<0.01). In 2 further normal-weight groups, AD was recorded before and after elevation of FFA levels with intralipid infusion (by +535%, n=9) and a 5-day high-fat, low-carbohydrate diet (by +48%, n=14). Both intralipid infusion and a low-carbohydrate diet resulted in reduced abdominal AD (infusion -22%, diet -28%; both P<0.05), reproducing the distal pattern AD reduction seen in obesity. These findings suggest that elevated FFA impair AD in obesity and provide a potential therapeutic target to improve aortic elastic function in obesity.

A global evolutionary and metabolic analysis of human obesity gene risk variants.

PubMed

Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

2017-09-05

It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

Lack of Support for the Association Between GAD2 Polymorphisms andSevere Human Obesity

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

Swarbrick, Michael M.; Waldenmaier, Bjorn; Pennacchio, Len A.

Demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention and treatment of these conditions. Unequivocal proof of such an association, however, requires adherence to established methodological guidelines, which include independent replication of initial positive findings. Recently, single nucleotide polymorphisms (SNPs) within GAD2 were found to be associated with class III obesity (BMI > 40 kg/m2) in 188 families (612 individuals) segregating the condition and a case-control study of 575 cases and 646 lean controls. Functional data supporting a pathophysiological role for one of the SNPs (-243A>G) weremore » also presented. In the present study, we attempted to replicate this association in larger groups of subjects, and to extend the functional studies of the -243A>G SNP. In 2,327 subjects comprising 692 German nuclear families with severe, early-onset obesity, we found no evidence for a relationship between the three GAD2 SNPs and obesity, whether SNPs were studied individually or as haplotypes. In two independent case-control studies (a total of 680 class III obesity cases and 1,186 lean controls), there was no significant relationship between the -243A>G SNP and obesity (odds ratio (OR) = 0.99, 95% CI 0.83 - 1.18,in the pooled sample). These negative findings were reinforced by a meta-analysis for the association between the 243G allele and class III obesity, which yielded an OR of 1.11 (95% CI 0.90 - 1.36) in a total sample of 1,252 class III obese cases and 1,800 lean controls. Finally,we were unable to confirm or extend the functional data pertaining to the -243A>G variant. Potential confounding variables in association studies involving common variants and complex diseases (low power to detect modest genetic effects, over-interpretation of marginal data, population stratification and biological plausibility) are also discussed in the context of

Ondansetron attenuates depression co-morbid with obesity in obese mice subjected to chronic unpredictable mild stress; an approach using behavioral battery tests.

PubMed

Kurhe, Yeshwant; Radhakrishnan, Mahesh; Gupta, Deepali

2014-09-01

The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with ondansetron was started on day 15. After day 28 behavioral assays and biochemical estimations were performed. Behavioral paradigms viz. sucrose preference test, locomotor score, forced swim test (FST) and elevated plus maze (EPM), whereas biochemical parameters like plasma glucose, total cholesterol, triglycerides and total proteins were estimated. Results examines that in behavioral assays, ondansetron significantly (P < 0.05) increased sucrose consumption, reduced immobility time in FST, increased the percent entries and time in open arm in EPM. In biochemical assessments elevated plasma glucose, total cholesterol, triglycerides and total proteins were significantly (P < 0.05) reversed by ondansetron treatment in HFD obese animals subjected to CUMS. The study indicates that the obese mice subjected to CUMS exhibited severe depressive-like symptoms and ondansetron significantly reversed the behavioral and biochemical alterations. In the present study the plasma glucose level indicates that, it could be "altered glucose level" playing an important role in depression co-morbid with obesity. Ondansetron through allosteric modulation of serotonergic system elevates the serotonin level and thereby regulates the insulin secretion and hence, reversing the "altered glucose level", could be the possible antidepressive-like mechanism against depression co-morbid with obesity.

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

PubMed

Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

1996-08-01

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast.

PubMed

Bak, Ann Mosegaard; Møller, Andreas Buch; Vendelbo, Mikkel Holm; Nielsen, Thomas Svava; Viggers, Rikke; Rungby, Jørgen; Pedersen, Steen Bønløkke; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

2016-07-01

Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein. Copyright © 2016 the American Physiological Society.

Disability affects the 6-minute walking distance in obese subjects (BMI>40 kg/m(2)).

PubMed

Donini, Lorenzo Maria; Poggiogalle, Eleonora; Mosca, Veronica; Pinto, Alessandro; Brunani, Amelia; Capodaglio, Paolo

2013-01-01

In obese subjects, the relative reduction of the skeletal muscle strength, the reduced cardio-pulmonary capacity and tolerance to effort, the higher metabolic costs and, therefore, the increased inefficiency of gait together with the increased prevalence of co-morbid conditions might interfere with walking. Performance tests, such as the six-minute walking test (6MWT), can unveil the limitations in cardio-respiratory and motor functions underlying the obesity-related disability. Therefore the aims of the present study were: to explore the determinants of the 6-minute walking distance (6MWD) and to investigate the predictors of interruption of the walk test in obese subjects. Obese patients [body mass index (BMI)>40 kg/m(2)] were recruited from January 2009 to December 2011. Anthropometry, body composition, specific questionnaire for Obesity-related Disabilities (TSD-OC test), fitness status and 6MWT data were evaluated. The correlation between the 6MWD and the potential independent variables (anthropometric parameters, body composition, muscle strength, flexibility and disability) were analysed. The variables which were singularly correlated with the response variable were included in a multivariated regression model. Finally, the correlation between nutritional and functional parameters and test interruption was investigated. 354 subjects (87 males, mean age 48.5 ± 14 years, 267 females, mean age 49.8 ± 15 years) were enrolled in the study. Age, weight, height, BMI, fat mass and fat free mass indexes, handgrip strength and disability were significantly correlated with the 6MWD and considered in the multivariate analysis. The determination coefficient of the regression analysis ranged from 0.21 to 0.47 for the different models. Body weight, BMI, waist circumference, TSD-OC test score and flexibility were found to be predictors of the 6MWT interruption. The present study demonstrated the impact of disability in obese subjects, together with age, anthropometric

Disability Affects the 6-Minute Walking Distance in Obese Subjects (BMI>40 kg/m2)

PubMed Central

Donini, Lorenzo Maria; Poggiogalle, Eleonora; Mosca, Veronica; Pinto, Alessandro; Brunani, Amelia; Capodaglio, Paolo

2013-01-01

Introduction In obese subjects, the relative reduction of the skeletal muscle strength, the reduced cardio-pulmonary capacity and tolerance to effort, the higher metabolic costs and, therefore, the increased inefficiency of gait together with the increased prevalence of co-morbid conditions might interfere with walking. Performance tests, such as the six-minute walking test (6MWT), can unveil the limitations in cardio-respiratory and motor functions underlying the obesity-related disability. Therefore the aims of the present study were: to explore the determinants of the 6-minute walking distance (6MWD) and to investigate the predictors of interruption of the walk test in obese subjects. Methods Obese patients [body mass index (BMI)>40 kg/m2] were recruited from January 2009 to December 2011. Anthropometry, body composition, specific questionnaire for Obesity-related Disabilities (TSD-OC test), fitness status and 6MWT data were evaluated. The correlation between the 6MWD and the potential independent variables (anthropometric parameters, body composition, muscle strength, flexibility and disability) were analysed. The variables which were singularly correlated with the response variable were included in a multivariated regression model. Finally, the correlation between nutritional and functional parameters and test interruption was investigated. Results 354 subjects (87 males, mean age 48.5±14 years, 267 females, mean age 49.8±15 years) were enrolled in the study. Age, weight, height, BMI, fat mass and fat free mass indexes, handgrip strength and disability were significantly correlated with the 6MWD and considered in the multivariate analysis. The determination coefficient of the regression analysis ranged from 0.21 to 0.47 for the different models. Body weight, BMI, waist circumference, TSD-OC test score and flexibility were found to be predictors of the 6MWT interruption. Discussion The present study demonstrated the impact of disability in obese subjects

The human obesity epidemic, the mismatch paradigm, and our modern "captive" environment.

PubMed

Power, Michael L

2012-01-01

In the distant past obesity in humans was rare and likely caused by metabolic dysregulation due to genetic or disease-related pathology. External factors precluded the ability of most people to overeat or under exert. Socio-cultural obesity came about due to the rareness of obesity and its difficulty to achieve. What is rare becomes valuable and what is difficult to achieve becomes a badge of prestige. The modern human obesity epidemic would appear to represent a third class of obesity: environmental obesity. Much like the captive environments which humans construct for the captive/companion animals in our care, the modern human environment has greatly decreased the challenges of life that would restrict food intake and enforce exertion. And like us, our captive/companion animal populations are also experiencing obesity epidemics. A further concern is that maternal obesity alters maternal signaling to offspring, in utero through the placenta and after birth through breast milk, in ways that perpetuate an enhanced vulnerability to obesity. Molecules such as leptin, produced by adipose tissue and placenta, have significant developmental effects on brain areas associated with feeding behavior. Leptin and other cytokines and growth factors are found in breast milk. These molecules have positive effects on gut maturation; their effects on metabolism and brain development are unclear. Placenta and brain also are hotspots for epigenetic regulation, and epigenetic changes may play significant roles in the later vulnerability to obesity and to the development of a diverse array of diseases, including heart disease, hypertension, and noninsulin-dependent diabetes. Copyright © 2012 Wiley Periodicals, Inc.

Obesity-related genetic variants, human pigmentation, and risk of melanoma

PubMed Central

Li, Xin; Liang, Liming; Zhang, Mingfeng; Song, Fengju; Nan, Hongmei; Wang, Li-E; Wei, Qingyi; Lee, Jeffrey E.; Amos, Christopher I.; Qureshi, Abrar A.; Han, Jiali

2013-01-01

Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles=0.12, P-value=4 10−5). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R-square quality metric >0.8 using the 1000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity. PMID:23539184

Food and drug reward: overlapping circuits in human obesity and addiction

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

Volkow N. D.; Wang G.; Volkow, N.D.

Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects - partly mediated by dopamine increases in the limbic system - that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have startedmore » to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioral inhibition), stress reactivity and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that investigate the role of dopamine in drug addiction and in obesity and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.« less

[Effect of a hypocaloric diet in the oxidative stress in obese subjects without prescription of exercise and antioxidants].

PubMed

Gutiérrez, Liliana; García, José R; Rincón, María de Jesús; Ceballos, Guillermo M; Olivares, Ivonne M

2015-07-06

Obesity is characterized by a generalized increase of adipose tissue, high production of adipocytokines and presence of oxidative systemic stress. The objective of this study was to evaluate the changes generated in the oxidative stress and anthropometric parameters in obese subjects by the prescription of a hypocaloric diet in combination with moderate aerobic exercise and supplementation with antioxidants. Oxidative damage was determined in the plasma from 30 normal weight and 30 obese subjects. Three groups of treatment were established: Hypocaloric diet (HD), HD plus moderate aerobic exercise (HDE) and HDE plus antioxidants (DHEA). Biomarkers of oxidative stress (thiobarbituric acid reactive substances [TBARS], carbonyl groups, dityrosine) and anthropometric parameters were determined. Higher values of biomarkers of oxidative damage were observed in obese (TBARS 13.74 ± 1.2 μM; carbonyl groups 0.89 ± 0.04 nmol of osazone/mg of protein; dityrosine 478.9 ± 27.4 RFU/mg of protein) in comparison to normal weight subjects (TBARS 7.08 ± 0.8 μM; carbonyl groups 0.65 ± 0.04 nmol of osazone/mg of protein; dityrosine 126.3 ± 12.6 RFU/mg of protein), thus showing the presence of an oxidative damage. The prescription of HD decreased the oxidative damage and anthropometric parameters in the obese subjects. We did not observe additional benefit effects on these determinations with HDE or HDEA treatments. We demonstrated that an HD decreases the oxidative damage in obese subjects. Oxidative stress is an important factor in the development of comorbidity in obesity. Therefore, the prescription of a HD could be a key issue in the treatment of the disease. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Core body temperature in obesity.

PubMed

Heikens, Marc J; Gorbach, Alexander M; Eden, Henry S; Savastano, David M; Chen, Kong Y; Skarulis, Monica C; Yanovski, Jack A

2011-05-01

A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. In study 1, nonobese [body mass index (BMI; in kg/m(2)) <30] and obese (BMI ≥30) adults swallowed wireless core temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500.

Obese subjects show sex-specific differences in right ventricular hypertrophy.

PubMed

Rider, Oliver J; Lewis, Andrew J M; Lewandowski, Adam J; Ntusi, Ntobeko; Nethononda, Richard; Petersen, Steffen E; Francis, Jane M; Pitcher, Alex; Banerjee, Rajarshi; Leeson, Paul; Neubauer, Stefan

2015-01-01

As right ventricular (RV) remodeling in obesity remains underinvestigated, and the impact of left ventricular (LV) diastolic dysfunction on RV hypertrophy is unknown, we aimed to investigate whether (1) sex-specific patterns of RV remodeling exist in obesity and (2) LV diastolic dysfunction in obesity is related to RV hypertrophy. Seven hundred thirty-nine subjects (women, n=345; men, n=394) without identifiable cardiovascular risk factors (body mass index [BMI], 15.3-59.2 kg/m2) underwent cardiovascular magnetic resonance (1.5 T) to measure RV mass (g), RV end-diastolic volume (mL), RV mass/volume ratio, and LV diastolic peak filling rate (mL/s). All subjects were normotensive (average, 119±11/73±8 mm Hg), normoglycaemic (4.8±0.5 mmol/L), and normocholesterolaemic (4.8±0.9 mmol/L) at the time of scanning. Across both sexes, there was a moderately strong positive correlation between BMI and RV mass (men, +0.8 g per BMI point increase; women, +1.0 g per BMI point increase; both P<0.001). Whereas women exhibited RV cavity dilatation (RV end-diastolic volume, +1.0 mL per BMI point increase; P<0.001), BMI was not correlated with RV end-diastolic volume in men (R=0.04; P=0.51). Concentric RV remodeling was present in both sexes, with RV mass/volume ratio being positively correlated to BMI (men, R=0.41; women, R=0.51; both P<0.001). Irrespective of sex, the LV peak filling rate was negatively correlated with both RV mass (men, R=-0.43; women, R=-0.44; both P<0.001) and RV mass/volume ratio (men, R=-0.37; women, R=-0.35; both P<0.001). A sex difference in RV remodeling exists in obesity. Whereas men exhibit concentric RV remodeling, women exhibit a mixed pattern of eccentric and concentric remodeling. Regardless of sex, reduced LV diastolic function is associated with concentric RV remodeling. © 2014 American Heart Association, Inc.

Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity

PubMed Central

Díaz-Ruiz, Alberto; Guzmán-Ruiz, Rocío; Moreno, Natalia R.; García-Rios, Antonio; Delgado-Casado, Nieves; Membrives, Antonio; Túnez, Isaac; El Bekay, Rajaa; Fernández-Real, José M.; Tovar, Sulay; Diéguez, Carlos; Tinahones, Francisco J.; Vázquez-Martínez, Rafael; López-Miranda, José

2015-01-01

Abstract Aims: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. However, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, metabolically unhealthy obese (MUHO) phenotype. Results: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifically, the glutathione redox cycle and other antioxidant defense systems as well as the protein-folding machinery were dysregulated and endoplasmic reticulum stress was increased in adipocytes from IR subjects. Moreover, proteasome activity was also compromised in adipocytes of MUHO individuals, which was associated with enhanced accumulation of oxidized and ubiquitinated proteins in these cells. Proteasome activity was also impaired in adipocytes of diet-induced obese mice and in 3T3-L1 adipocytes exposed to palmitate. In line with these data, proteasome inhibition significantly impaired insulin signaling in 3T3-L1 adipocytes. Innovation: This study provides the first evidence of the occurrence of protein homeostasis deregulation in adipocytes in human obesity, which, together with oxidative damage, interferes with insulin signaling in these cells. Conclusion: Our results suggest that proteasomal dysfunction and impaired proteostasis in adipocytes, resulting from protein oxidation and/or misfolding, constitute major pathogenic mechanisms in the development of IR in obesity. Antioxid. Redox Signal. 23, 597–612. PMID:25714483

The Epigenomic Analysis of Human Obesity.

PubMed

Bell, Christopher G

2017-09-01

Analysis of the epigenome-the chemical modifications and packaging of the genome that can influence or indicate its activity-enables molecular insight into cell type-specific machinery. It can, therefore, reveal the pathophysiological mechanisms at work in disease. Detected changes can also represent physiological responses to adverse environmental exposures, thus enabling the epigenetic mark of DNA methylation to act as an epidemiological biomarker, even in surrogate tissue. This makes epigenomic analysis an attractive prospect to further understand the pathobiology and epidemiological aspects of obesity. Furthermore, integrating epigenomic data with known obesity-associated common genetic variation can aid in deciphering their molecular mechanisms. This review primarily examines epidemiological or population-based studies of epigenetic modifications in relation to adiposity traits, as opposed to animal or cell models. It discusses recent work exploring the epigenome with respect to human obesity, which to date has predominately consisted of array-based studies of DNA methylation in peripheral blood. It is of note that highly replicated BMI DNA methylation associations are not causal, but strongly driven by coassociations for more precisely measured intertwined outcomes and factors, such as hyperlipidemia, hyperglycemia, and inflammation. Finally, the potential for the future exploration of the epigenome in obesity and related disorders is considered. © 2017 The Obesity Society.

Association of obesity with hypertension and dyslipidemia in type 2 diabetes mellitus subjects.

PubMed

Anari, Razieh; Amani, Reza; Latifi, Seyed Mahmoud; Veissi, Masoud; Shahbazian, Hajieh

Obesity and diabetes are contributed to cardiovascular disease risk. The current study was performed to evaluate the association of central and general obesity and cardio-metabolic risk factors, including dyslipidemia and hypertension in T2DM patients. This was a cross-sectional study in T2DM adults. Body mass index (BMI) was used to identify general obesity and waist circumference (WC) was measured to define abdominal obesity (based on ATP III). Biochemical analyses, and anthropometric and blood pressure measurements were done for all participants. Participants with central obesity showed significantly higher systolic (132.5mmHg vs. 125.4mmHg, p=0.024) and diastolic blood pressures (84.9mmHg vs. 80mmHg, p=0.007) than participants without obesity. Dyslipidemia was more prevalent in all participants either by BMI (98.3% vs. 97%, 95% CI: 0.18-17.53) or by WC (97.2% vs. 98%, 95% CI: 0.07-7.19). Abdominal adiposity in diabetic subjects showed significant reverse association with high level of physical activity (OR=0.22, 95% CI: 0.06-0.85). Hypertriglyceridemia rate was increased with both central (OR=2.11; p=0.040) and general obesity (OR=2.68; p=0.021). After adjustment for energy intake and age, females had higher risk of general (OR=4.57, 95% CI=1.88-11.11) and central obesity (OR=7.93, 95% CI=3.48-18.08). Females were more susceptible to obesity. Hypertension was associated with both obesity measures. Dyslipidemia, except for hypertriglyceridemia, was correlated to neither abdominal nor general obesity. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Effects of living at two ambient temperatures on 24-h blood pressure and neuroendocrine function among obese and non-obese humans: a pilot study

NASA Astrophysics Data System (ADS)

Kanikowska, Dominika; Sato, Maki; Iwase, Satoshi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko; Sugenoya, Junichi

2013-05-01

The effects of environmental temperature on blood pressure and hormones in obese subjects in Japan were compared in two seasons: summer vs winter. Five obese (BMI, 32 ± 5 kg/m2) and five non-obese (BMI, 23 ±3 kg/m2) men participated in this experiment at latitude 35°10' N and longitude 136°57.9' E. The average environmental temperature was 29 ± 1 °C in summer and 3 ± 1 °C in winter. Blood samples were analyzed for leptin, ghrelin, catecholamines, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), total cholesterol, triglycerides, insulin and glucose. Blood pressure was measured over the course of 24 h in summer and winter. A Japanese version of the Profile of Mood States (POMS) questionnaire was also administered each season. Systolic and diastolic blood pressures in obese men were significantly higher in winter (lower environmental temperatures) than in summer (higher environmental temperatures). Noradrenaline and dopamine concentrations were also significantly higher at lower environmental temperatures in obese subjects, but ghrelin, TSH, fT3, fT4, insulin and glucose were not significantly different in summer and winter between obese and non-obese subjects. Leptin, total cholesterol and triglyceride concentrations were significantly higher in winter in obese than non-obese men. Results from the POMS questionnaire showed a significant rise in Confusion at lower environmental temperatures (winter) in obese subjects. In this pilot study, increased blood pressure may have been due to increased secretion of noradrenaline in obese men in winter, and the results suggest that blood pressure control in obese men is particularly important in winter.

Gender-related differences concerning anger expression and interpersonal relationships in a sample of overweight/obese subjects.

PubMed

Iliceto, P; Pompili, M; Candilera, G; Natali, M A; Stefani, H; Lester, D; Serafini, G; Girardi, P

2012-01-01

Obesity and overweight are relevant public health issues. They are frequently associated with increased disability, enhanced morbidity and mortality and are often comorbid with several psychological/psychiatric conditions. The aim of the present study was to explore gender-related differences concerning anger expression and interpersonal relationships in a sample of overweight/obese subjects. The convenience sample consisted of 40 overweight/obese subjects (18 women, 22 men) who were administered self-report questionnaires to assess eating disorders (EDI-2), anger levels (STAXI) and self/other perception as a measure of interpersonal relationships (9AP). Women had higher scores on the EDI-2 subscales of Bulimia (7.22 vs. 2.20: z=7.61; p<.001), Body Dissatisfaction (15.56 vs. 12.14: z=1.88; p=.03), Interoceptive Awareness (9.89 vs. 5.28: z=4.06; p<.001), Ineffectiveness (11.00 vs 5.22: z=4.91; p <.001) and Perfectionism (6.33 vs. 3.26: z=4.13; p<.001) compared to norms. The overweight/obese men departed from the norms on fewer subscales. Both women and men tended to turn feelings of anger in toward themselves, suppressing their anger. Also, women obtained lower scores for Self Empathy (29.06 vs. 40.15: z = - 2.30; p = .01) and Other Empathy (16.44 vs. 27.10: z =- 2.00; p= .02) whereas overweight/ obese men obtained lower scores for Other Empathy (20.77 vs. 28.47: z=-2.00; p=.02). Overweight/obese subjects have a tendency to turn feelings of anger inward on to themselves together with impaired interpersonal relationships, especially in women. An adequate clinical assessment in all obese individuals trying to identify the contribution of psychological factors to the perceived distress is critical.

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects

PubMed Central

Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; DeFronzo, Ralph A; Dubé, John J; Musi, Nicolas

2013-01-01

Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IκBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IκBα protein (an indication of decreased IκB kinase–nuclear factor κB signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs. PMID:23529132

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

PubMed

Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; Defronzo, Ralph A; Dubé, John J; Musi, Nicolas

2013-06-01

Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

Metabolic and Inflammatory Changes with Orlistat and Sibutramine Treatment in Obese Malaysian Subjects.

PubMed

Al-Tahami, Belqes Abdullah Mohammad; Al-Safi Ismail, Ab Aziz; Sanip, Zulkefli; Yusoff, Zurkurnai; Shihabudin, Tg Muzaffar Tm; Singh, Taran Singh Pall; Rasool, Aida Hanum Ghulam

2017-01-01

Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity

PubMed Central

Farb, Melissa G.; Tiwari, Stephanie; Karki, Shakun; Ngo, Doan TM; Carmine, Brian; Hess, Donald T.; Zuriaga, Maria A.; Walsh, Kenneth; Fetterman, Jessica L.; Hamburg, Naomi M.; Vita, Joseph A.; Apovian, Caroline M.; Gokce, Noyan

2013-01-01

Objective The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. Design and Methods In 20 obese subjects (age 37±12 yrs, BMI 47±8 kg/m2) we collected subcutaneous and visceral fat during bariatric surgery and characterized adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat. Results Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (p<0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway were upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by 2-fold (p=0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with Nω-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability. Conclusions Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity. PMID:23640904

Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome

PubMed Central

Moreno-Indias, Isabel; Coín-Aragüez, Leticia; Lhamyani, Said; Alcaide Torres, Juan; Fernández-Veledo, Sonia; Vendrell, Joan; Camargo, Antonio; El Bekay, Rajaa; Tinahones, Francisco José

2017-01-01

Background/Objectives Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS). Methods This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated. Results Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox

Core body temperature in obesity123

PubMed Central

Heikens, Marc J; Gorbach, Alexander M; Eden, Henry S; Savastano, David M; Chen, Kong Y; Skarulis, Monica C

2011-01-01

Background: A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. Objective: We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. Design: In study 1, nonobese [body mass index (BMI; in kg/m2) <30] and obese (BMI ≥30) adults swallowed wireless core temperature–sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18–25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Results: Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). Conclusions: Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature–regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500. PMID:21367952

Treatment of obesity hypoventilation syndrome and serum leptin.

PubMed

Yee, Brendon J; Cheung, Jane; Phipps, Paul; Banerjee, Dev; Piper, Amanda J; Grunstein, Ronald R

2006-01-01

Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels. The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations. We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study. The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred. Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

Indirect calorimetry in obese female subjects: Factors influencing the resting metabolic rate

PubMed Central

Hagedorn, Theresa; Poggiogalle, Eleonora; Savina, Claudia; Coletti, Cecilia; Paolini, Maddalena; Scavone, Luciano; Neri, Barbara; Donini, Lorenzo Maria

2012-01-01

AIM: To evaluate selected factors influencing resting energy expenditure (REE) in obese female subjects. METHODS: Seventy seven 61 obese Caucasian women [mean age of 52.93 ± 13.45 years, and mean body mass index (BMI) of 41.78 ± 11.54 kg/m2] were enrolled; measurements of resting metabolic rate (RMR) by a ventilated, open-circuit system, indirect calorimeter were performed after an overnight fast. Body composition as well as medications, physical parameters, blood samples, disease pattern, and smoking were considered. RESULTS: RMR was significantly associated with body weight (r = 0.732, P < 0.001), body height (r = 0.401, P = 0.008), BMI (r = 0.504, P < 0.001), waist circumference (r = 0.602, P < 0.001), mid-upper arm circumference (r = 0.417, P = 0.006), mid-upper arm muscle circumference (r = 0.344, P = 0.028), total body water (r = 0.339, P = 0.035), body temperature (r = 0.409, P = 0.007), smoking (P = 0.031), serum T4 levels (r = 0.331, P = 0.036), obstructive sleep apnoea syndrome (OSAS; P = 0.023), impaired glucose tolerance (IGT; P = 0.017) and impaired glycaemic status, including hyperinsulinism, IGT and diabetes mellitus (P = 0.003). CONCLUSION: Future research should be prompted to optimize the procedure of indirect calorimetry to achieve clinical benefits in obese subjects. PMID:24520534

Indirect calorimetry in obese female subjects: Factors influencing the resting metabolic rate.

PubMed

Hagedorn, Theresa; Poggiogalle, Eleonora; Savina, Claudia; Coletti, Cecilia; Paolini, Maddalena; Scavone, Luciano; Neri, Barbara; Donini, Lorenzo Maria

2012-06-20

To evaluate selected factors influencing resting energy expenditure (REE) in obese female subjects. Seventy seven 61 obese Caucasian women [mean age of 52.93 ± 13.45 years, and mean body mass index (BMI) of 41.78 ± 11.54 kg/m(2)] were enrolled; measurements of resting metabolic rate (RMR) by a ventilated, open-circuit system, indirect calorimeter were performed after an overnight fast. Body composition as well as medications, physical parameters, blood samples, disease pattern, and smoking were considered. RMR was significantly associated with body weight (r = 0.732, P < 0.001), body height (r = 0.401, P = 0.008), BMI (r = 0.504, P < 0.001), waist circumference (r = 0.602, P < 0.001), mid-upper arm circumference (r = 0.417, P = 0.006), mid-upper arm muscle circumference (r = 0.344, P = 0.028), total body water (r = 0.339, P = 0.035), body temperature (r = 0.409, P = 0.007), smoking (P = 0.031), serum T4 levels (r = 0.331, P = 0.036), obstructive sleep apnoea syndrome (OSAS; P = 0.023), impaired glucose tolerance (IGT; P = 0.017) and impaired glycaemic status, including hyperinsulinism, IGT and diabetes mellitus (P = 0.003). Future research should be prompted to optimize the procedure of indirect calorimetry to achieve clinical benefits in obese subjects.

DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise

PubMed Central

Abubaker, Jehad; Tiss, Ali; Abu-Farha, Mohamed; Al-Ghimlas, Fahad; Al-Khairi, Irina; Baturcam, Engin; Cherian, Preethi; Elkum, Naser; Hammad, Maha; John, Jeena; Kavalakatt, Sina; Khadir, Abdelkrim; Warsame, Samia; Dermime, Said; Behbehani, Kazem; Dehbi, Mohammed

2013-01-01

Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT2-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity. PMID:23894433

Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation.

PubMed

Fornari, R; Francomano, D; Greco, E A; Marocco, C; Lubrano, C; Wannenes, F; Papa, V; Bimonte, V M; Donini, L M; Lenzi, A; Aversa, A; Migliaccio, S

2015-03-01

Several chronic metabolic alterations are present in obese subjects. While it is well known about the detrimental effect of abdominal adipose tissue on chronic metabolic clinical condition, less is known on the role of lean mass in obese subjects. Thus, the aim of our study was to evaluate the potential correlation of muscle mass, metabolic condition and inflammation status in obese individuals. The study included 426 obese subjects (86 men and 340 female; mean age 44.8 ± 14 years; BMI: 34.9 ± 6.1 kg/m(2)). Exclusion criteria were chronic medical conditions or use of medications affecting bone metabolism, alterations of hormonal and nutritional status, vitamin D supplementation, recent weight loss and prior bariatric surgery. Patients underwent measurements of bone mineral density (lumbar and hip) and body composition (lean mass, total and trunk fat mass) by dual X-ray absorptiometry and were evaluated for hormonal and metabolic profile and inflammatory markers. Higher lean body mass (LM%) was inversely correlated with homeostasis model assessment of insulin resistance (p < 0.0091; r(2) 0.03938) and associated with lower fibrinogen levels (p < 0.0001; r(2) 0.1263). Interestingly, in obese subjects, LM% was associated with higher levels of vitamin D (p < 0.0001, r(2) 0.1140), osteocalcin (p < 0.0001, r(2) 0.2401) and insulin-like growth factor-1 (IGF-1) (p < 0.0002, r(2) 0.1367). Our results show for the first time that in obese patients, higher amounts of lean mass are directly linked to a lower inflammatory profile and to better insulin sensitivity, but also to the presence of higher level of vitamin D and IGF-1. Moreover, these data suggest that higher levels of lean mass in obese people correlate with a better metabolic profile and, thus, strongly suggest the need to develop programs to facilitate an increase in physical activity in obese people.

Laboratory animals as surrogate models of human obesity

PubMed Central

Nilsson, Cecilia; Raun, Kirsten; Yan, Fei-fei; Larsen, Marianne O; Tang-Christensen, Mads

2012-01-01

Obesity and obesity-related metabolic diseases represent a growing socioeconomic problem throughout the world. Great emphasis has been put on establishing treatments for this condition, including pharmacological intervention. However, there are many obstacles and pitfalls in the development process from pre-clinical research to the pharmacy counter, and there is no certainty that what has been observed pre-clinically will translate into an improvement in human health. Hence, it is important to test potential new drugs in a valid translational model early in their development. In the current mini-review, a number of monogenetic and polygenic models of obesity will be discussed in view of their translational character. PMID:22301857

Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects

PubMed Central

Shabana; Ullah Shahid, Saleem; Wah Li, Ka; Acharya, Jayshree; Cooper, Jackie A; Hasnain, Shahida; Humphries, Stephen E

2016-01-01

The aim of the current study was to analyze the effect of six type II diabetes GWAS loci rs3923113 (GRB14), rs16861329 (ST6GAL1), rs1802295 (VPS26A), rs7178572 (HMG20A), rs2028299 (AP3S2) and rs4812829 (HNF4A), and an FTO polymorphism (rs9939609) on obesity. The probable mechanism of action of these SNPs was analyzed by studying their association with various biochemical and anthropometric parameters. A total of 475 subjects (obese=250, controls=225) were genotyped by TaqMan assay and their lipid profile was determined. Allele/genotype frequencies and an unweighted/weighted gene score were calculated. The effect of the gene score on anthropometric and biochemical parameters was analyzed. The minor allele frequencies of all variants were comparable to that reported in the original studies and were associated with obesity in these Pakistani subjects. Subjects with 9 risk alleles differ from those with <3 and overall there is no significant effect (P-value for trend 0.26). None of the SNPs were associated with any of the serum lipid traits. We are the first to report the association of these T2D SNPs with obesity. In the Pakistani population the reported effect of six SNPs for obesity is similar to that reported for T2D and having a combination of risk alleles on obesity can be considerable. The mechanism of this effect is unclear, but appears not to be mediated by changing serum lipid chemistry. PMID:26395551

Protecting human subjects in research.

PubMed

Orticio, Lily P

2009-01-01

The quest for advancing scientific knowledge through human experimentations using vulnerable groups is traced back to ancient history, when Herophilus performed vivisections on prisoners. The violation of the rights of human subjects through the 20th century led to the formulation of the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964. In the United States, the most infamous was the Tuskegee public health study that resulted in the enactment of the National Research Act that authorized the creation of the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research in 1974. In spite of existing federal regulations, the system of protecting human subjects is still flawed. Transparency of conflict ofinterest, clarity, and strict adherence to institutional guidelines are critical in safeguarding the rights and safety of human subjects and the integrity of research. Education on ethics and emerging complex ethical issues, global awareness, and governmental cooperation and sanctions are important steps in addressing the inadequacies in protecting the most vulnerable populations in experimentations worldwide. Investigators must always remember that the primary safeguards of protecting human life rest in their hands.

Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns

USDA-ARS?s Scientific Manuscript database

Recently, in a randomized, double-blind cross-over study, we reported that consumption of grape powder by obese human subjects increased the production of the pro-inflammatory cytokines interleukin-1' and interleukin-6 by ex vivo-derived peripheral blood monocytes after exposure to bacterial lipopol...

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects.

PubMed

Siddiq, A; Gueorguiev, M; Samson, C; Hercberg, S; Heude, B; Levy-Marchal, C; Jouret, B; Weill, J; Meyre, D; Walley, A; Froguel, P

2007-03-01

Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 non-obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/non-diabetic control subjects (n=1,163). Significant association was found for a 5' variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (co-dominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with obesity and its contribution to obesity should be investigated further.

Musculoskeletal findings in obese subjects before and after weight loss following bariatric surgery.

PubMed

Hooper, M M; Stellato, T A; Hallowell, P T; Seitz, B A; Moskowitz, R W

2007-01-01

To determine the point prevalence of painful musculoskeletal (MSK) conditions in obese subjects before and after weight loss following bariatric surgery. Longitudinal, interventional, unblended. Forty-eight obese subjects (47 women, one man, mean age 44+/-9 years; mean body mass index (BMI) 51+/-8 kg/m(2)) recruited from an academic medical center bariatric surgery program. Comorbid medical conditions; MSK findings; BMI; Western Ontario McMaster Osteoarthritis Index (WOMAC) for pain, stiffness and function; and SF-36 for quality of life. Consecutive subjects were recruited from the University Hospitals of Cleveland Bariatric Surgery Program. Musculoskeletal signs and symptoms and non-MSK comorbid conditions were documented at baseline and at follow-up. SUBJECTS completed the SF-36 and the WOMAC questionnaires. Analyses were carried out for each MSK site, fibromyalgia syndrome (FMS) and for the cumulative effect on the spine, upper and lower extremities. The impact of change in comorbid medical conditions, BMI, physical and mental health domains of the SF-36 on the WOMAC pain subscale score was evaluated. SF-36 outcomes were compared to normal published controls. Forty-eight subjects were available for baseline and a follow-up assessment 6-12 months after gastric bypass surgery. They lost an average of 41+/-15 kg and the mean BMI decreased from 51+/-8 to 36+/-7 kg/m(2). Baseline comorbid medical conditions were present in 96% before surgery and 23% after weight loss. There was an increased prevalence of painful MSK conditions at baseline compared to general population frequencies. Musculoskeletal complaints had been present in 100% of obese subjects before, and 23% after weight loss. The greatest improvements occurred in the cervical and lumbar spine, the foot and in FMS (decreased by 90, 83, 83 and 92%, respectively). Seventy-nine percent had upper extremity MSK conditions before and 40% after weight loss. Before surgery, 100% had lower extremity MSK conditions and

Overt and subtle discrimination, subjective well-being and physical health-related quality of life in an obese sample.

PubMed

Magallares, Alejandro; Benito de Valle, Pilar; Irles, Jose Antonio; Jauregui-Lobera, Ignacio

2014-10-27

Obesity represents a serious health issue affecting millions of people in Western industrialized countries. The severity of the medical problems it causes is paralleled by the fact that obesity has become a social stigma that affects the psychological health-related quality of life of individuals with weight problems. Our study, with 111 obese patients of a Spanish hospital, focused specifically on how overt and subtle discrimination is related to subjective well-being (affect balance and life satisfaction) and physical health-related quality of life. It was shown that overt (r = -.28, p < .01 with affect balance; r = -.26, p < .01 with life satisfaction) and subtle discrimination (r = -.28, p < .01 with affect balance; r = -.27, p < .01 with life satisfaction) were negatively linked with subjective well-being, and that there was a negative correlation between overt discrimination and physical health-related quality of life (r = -.26, p < .01). Additionally, it was found that overt discrimination was a mediator variable in the relationship between physical health-related quality of life and subjective well-being using the Baron and Kenny procedure. Finally, it is discussed the relationship between discrimination, subjective well-being and physical health-related quality of life in obese people.

Relationship between neck circumference, insulin resistance and arterial stiffness in overweight and obese subjects.

PubMed

Fantin, Francesco; Comellato, Gabriele; Rossi, Andrea P; Grison, Elisa; Zoico, Elena; Mazzali, Gloria; Zamboni, Mauro

2017-09-01

Background Only a few studies have investigated the relationship between neck circumference and cardiometabolic risk. The aim of this study was to assess the relationships between neck circumference, waist circumference, metabolic variables and arterial stiffness in a group of overweight and obese subjects evaluating a possible independent role of neck circumference in determining arterial stiffness. Methods and results We studied 95 subjects (53 women) with an age range of 20-77 years and body mass index range from 25.69 to 47.04 kg/m 2 . In each subject we evaluated body mass index, waist, hip and neck circumference, systolic and diastolic blood pressure, insulin, fasting glucose, cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWVcf) and carotid-radial pulse wave velocity (PWVcr). Both PWVcf and PWVcr were higher in subjects with high values of neck circumference compared with subjects with normal values of neck circumference. Subjects with high values of neck circumference and abdominal obesity presented higher values of mean arterial pressure, PWVcr and homeostasis model assessment (HOMA) index and lower values of high-density lipoprotein than subjects with only abdominal obesity. Two models of stepwise multiple regression were performed in order to evaluate the combined effect of independent variables on arterial stiffness. In the first model PWVcf was considered a dependent variable, and age, gender, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, waist circumference, neck circumference, HOMA index and the use of anti-hypertensive medications were considered independent variables. Age, systolic blood pressure, triglycerides and waist circumference were significant predictors of PWVcf, explaining 65% of its variance. In the second model, in which PWVcr was considered a dependent variable, neck circumference

Oxidative stress and inflammation in lean and obese subjects with polycystic ovary syndrome.

PubMed

Blair, Sarah A; Kyaw-Tun, Tommy; Young, Ian S; Phelan, Niamh A; Gibney, James; McEneny, Jane

2013-01-01

To determine whether polycystic ovary syndrome (PCOS) independently influences oxidative stress and inflammation or if the culprit is the comorbidities of obesity and/or insulin resistance common to this condition. Thirty women with PCOS were matched for age, body mass index and insulin resistance with 30 control subjects. Oxidative stress was examined by measuring the total oxidant status (TOS) and total antioxidant capacity (TAC) by spectrophotometric assay. The inflammatory biomarkers, C-reactive protein, plasminogen activator inhibitor-1, myeloperoxidase, neopterin, and serum amyloid A were measured by ELISA methodologies. Oxidative status was increased in the PCOS subjects relative to their weight-matched controls (TOS: obese PCOS patients vs. obese controls, 42.42 +/- 4.49 vs. 32.57 +/- 1.97, p<0.05; lean PCOS patients vs. lean controls, 33.69 +/- 1.59 vs. 28.69 +/- 1.18 micromol H2O2 Equiv/L, p < 0.05). Furthermore, antioxidant capacity was lower in the lean PCOS group relative to their weight-matched controls (TAC: lean PCOS patients vs. lean controls, 1.10 +/- 0.09 vs. 1.49 +/- 0.03 nmol Trolox Equiv/L, p < 0.05). These results suggest that PCOS independently influenced oxidative stress. Overall, the presence of PCOS may increase cardiovascular risk.

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness.

PubMed

Stuart, Charles A; Lee, Michelle L; South, Mark A; Howell, Mary E A; Cartwright, Brian M; Ramsey, Michael W; Stone, Michael H

2017-03-01

Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not

Role of the DGAT gene C79T single-nucleotide polymorphism in French obese subjects.

PubMed

Coudreau, Sylvie Kipfer; Tounian, Patrick; Bonhomme, Geneviève; Froguel, Philippe; Girardet, Jean-Philippe; Guy-Grand, Bernard; Basdevant, Arnaud; Clément, Karine

2003-10-01

Acyl-coenzyme A, diacylglycerol acyltransferase (DGAT), is a key enzyme involved in adipose-cell triglyceride storage. A 79-bp T-to-C single-nucleotide polymorphism (SNP) on the 3' region of the DGAT transcriptional site has been reported to increase promoter activity and is associated with higher BMI in Turkish women. To validate the possible role of this genetic variant in obesity, as well as the variant's possible cellular-functional significance, we performed an association study between the T79C change and several obesity-related phenotypes in 1357 obese French adults and children. The prevalence of the T79C SNP was similar between obese adults and children when each group was compared with the controls. (CC genotype carrier frequencies were 0.25 to 0.29 in the obese groups and 0.21 in controls; p > 0.05.) In each of the obese adult and child groups studied, the T79C variant was not found to be associated with any of the obesity-related phenotypes tested. Although the T79C SNP of the DGAT gene was studied in several groups of white subjects, the association between this SNP and obesity-related phenotypes, previously described, was not confirmed in our population.

Hunter-gatherer energetics and human obesity.

PubMed

Pontzer, Herman; Raichlen, David A; Wood, Brian M; Mabulla, Audax Z P; Racette, Susan B; Marlowe, Frank W

2012-01-01

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg(-1) m(-1)) and resting (kcal kg(-1) s(-1)) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences.

Contribution of Common PCSK1 Genetic Variants to Obesity in 8,359 Subjects from Multi-Ethnic American Population

PubMed Central

Choquet, Hélène; Kasberger, Jay; Hamidovic, Ajna; Jorgenson, Eric

2013-01-01

Common PCSK1 variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common PCSK1 variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI (P = 0.006) and obesity (P = 0.018) but also increased the obesity incidence during the 20 years of follow-up (HR = 1.53 [1.07–2.19], P = 0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI (P = 0.028) and obesity (P = 0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR = 1.23 [1.05–1.45], P = 9.5×10−3). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI (P = 4.2×10−3) and obesity (P = 3.4×10−3) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group (P = 0.756 and P = 0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full PCSK1 locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results

Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population.

PubMed

Choquet, Hélène; Kasberger, Jay; Hamidovic, Ajna; Jorgenson, Eric

2013-01-01

Common PCSK1 variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common PCSK1 variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI (P = 0.006) and obesity (P = 0.018) but also increased the obesity incidence during the 20 years of follow-up (HR = 1.53 [1.07-2.19], P = 0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI (P = 0.028) and obesity (P = 0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR = 1.23 [1.05-1.45], P = 9.5×10(-3)). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI (P = 4.2×10(-3)) and obesity (P = 3.4×10(-3)) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group (P = 0.756 and P = 0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full PCSK1 locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results

Minireview: Epigenetics of obesity and diabetes in humans.

PubMed

Slomko, Howard; Heo, Hye J; Einstein, Francine H

2012-03-01

Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation.

Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

PubMed Central

Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

2015-01-01

Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

Code of Federal Regulations, 2012 CFR

2012-04-01

... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG ADMINISTRATION... of obesity in humans. (a) Investigation by the Food and Drug Administration has revealed that a large... laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in...

21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

Code of Federal Regulations, 2014 CFR

2014-04-01

... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG ADMINISTRATION... of obesity in humans. (a) Investigation by the Food and Drug Administration has revealed that a large... laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in...

21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

Code of Federal Regulations, 2011 CFR

2011-04-01

... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG ADMINISTRATION... of obesity in humans. (a) Investigation by the Food and Drug Administration has revealed that a large... laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in...

21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

Code of Federal Regulations, 2010 CFR

2010-04-01

... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG ADMINISTRATION... of obesity in humans. (a) Investigation by the Food and Drug Administration has revealed that a large... laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in...

21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

Code of Federal Regulations, 2013 CFR

2013-04-01

... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG ADMINISTRATION... of obesity in humans. (a) Investigation by the Food and Drug Administration has revealed that a large... laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in...

[Ethics and laws related to human subject research].

PubMed

Chiu, Hui-Ju; Lee, Ya-Ling; Chang, Su-Fen

2011-10-01

Advances in medical technology rely on human subject research to test the effects on real patients of unproven new drugs, equipment and techniques. Illegal human subject research happens occasionally and has led to subject injury and medical disputes. Familiarity with the laws and established ethics related to human subject research can minimize both injury and disputes. History is a mirror that permits reflection today on past experience. Discussing the Nuremberg Code, the Declaration of Helsinki and Belmont Report, this article describes the laws, ethics, history and news related to human subject research as well as the current definition and characteristics of human subject research. Increasing numbers of nurses serve as research nurses and participate in human subject research. The authors hope this article can increase research nurse knowledge regarding laws and ethics in order to protect human research subjects adequately.

Effects of diet-induced moderate weight reduction on intrahepatic and intramyocellular triglycerides and glucose metabolism in obese subjects.

PubMed

Sato, Fumihiko; Tamura, Yoshifumi; Watada, Hirotaka; Kumashiro, Naoki; Igarashi, Yasuhiro; Uchino, Hiroshi; Maehara, Tadayuki; Kyogoku, Shinsuke; Sunayama, Satoshi; Sato, Hiroyuki; Hirose, Takahisa; Tanaka, Yasushi; Kawamori, Ryuzo

2007-08-01

Although moderate weight reduction is recommended as primary therapy of metabolic syndrome, little information is known regarding metabolic changes associated with moderate weight reduction in nondiabetic obese subjects. The aim of this study was to determine the effects of a moderate weight reduction program on intracellular lipid and glucose metabolism in muscle and liver. Data for 13 nondiabetic obese subjects were evaluated. Subjects were put on a 3-month mildly hypocaloric diet therapy (approximately 35 kcal/kg of ideal body weight). Intrahepatic lipid (IHL) and intramyocellular lipid were measured by using (1)H magnetic resonance spectroscopy. Peripheral insulin sensitivity and splanchnic glucose uptake were evaluated by euglycemic-hyperinsulinemic clamp with oral glucose load. Diet therapy for 3 months resulted in 6% reduction in body weight (from 99.9 +/- 7.3 to 93.8 +/- 6.6 kg, P < 0.0001). This change was accompanied by reduction of plasma glucose and insulin excursions during 75-g oral glucose tolerance tests, decrease in diastolic blood pressure, glycated hemoglobin, serum low-density lipoprotein cholesterol, and triglyceride. These changes were also accompanied by a decrease in IHL (from 12.9 to 8.2%, P < 0.01) and increase in splanchnic glucose uptake (from 13.5 to 35.0%, P < 0.03). On the other hand, the diet program did not affect intramyocellular lipid or glucose infusion rate during euglycemic hyperinsulinemic clamp. Our results suggest that moderate weight reduction in obese subjects decreased IHL and augmented splanchnic glucose uptake. This mechanism is at least in part involved in improvement of glucose metabolism by moderate weight reduction in obese subjects.

Epigenetics and human obesity.

PubMed

van Dijk, S J; Molloy, P L; Varinli, H; Morrison, J L; Muhlhausler, B S

2015-01-01

Recent technological advances in epigenome profiling have led to an increasing number of studies investigating the role of the epigenome in obesity. There is also evidence that environmental exposures during early life can induce persistent alterations in the epigenome, which may lead to an increased risk of obesity later in life. This paper provides a systematic review of studies investigating the association between obesity and either global, site-specific or genome-wide methylation of DNA. Studies on the impact of pre- and postnatal interventions on methylation and obesity are also reviewed. We discuss outstanding questions, and introduce EpiSCOPE, a multidisciplinary research program aimed at increasing the understanding of epigenetic changes in emergence of obesity. An electronic search for relevant articles, published between September 2008 and September 2013 was performed. From the 319 articles identified, 46 studies were included and reviewed. The studies provided no consistent evidence for a relationship between global methylation and obesity. The studies did identify multiple obesity-associated differentially methylated sites, mainly in blood cells. Extensive, but small, alterations in methylation at specific sites were observed in weight loss intervention studies, and several associations between methylation marks at birth and later life obesity were found. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Eventually this may help in predicting an individual's obesity risk at a young age and opens possibilities for introducing targeted prevention strategies. It has also become clear that several epigenetic marks are modifiable, by changing the exposure in utero, but also by lifestyle changes in adult life, which implies that there is the potential for interventions to be introduced in postnatal life to modify

Food insecurity as a driver of obesity in humans: The insurance hypothesis

PubMed Central

Nettle, Daniel; Andrews, Clare; Bateson, Melissa

2016-01-01

Short abstract Common sense says that obesity is the consequence of too much food. Adaptive reasoning says something rather different: individuals should store fat when access to food is insecure, to buffer themselves against future shortfall. Applied to humans, this principle suggests that food insecurity should be a risk factor for overweight and obesity. We provide a meta-analysis of the extensive epidemiological literature, finding that food insecurity robustly predicts high body weight, but only amongst women in high-income countries. We discuss the relevance of food insecurity to understanding the global obesity problem. Long abstract Integrative explanations of why obesity is more prevalent in some sectors of the human population than others are lacking. Here, we outline and evaluate one candidate explanation, the insurance hypothesis (IH). The IH is rooted in adaptive evolutionary thinking: the function of storing fat is to provide a buffer against shortfall in the food supply. Thus, individuals should store more fat when they receive cues that access to food is uncertain. Applied to humans, this implies that an important proximate driver of obesity should be food insecurity rather than food abundance per se. We integrate several distinct lines of theory and evidence that bear on this hypothesis. We present a theoretical model that shows it is optimal to store more fat when food access is uncertain, and we review the experimental literature from non-human animals showing that fat reserves increase when access to food is restricted. We provide a meta-analysis of 125 epidemiological studies of the association between perceived food insecurity and high body weight in humans. There is a robust positive association, but it is restricted to adult women in high-income countries. We explore why this could be in light of the IH and our theoretical model. We conclude that whilst the IH alone cannot explain the distribution of obesity in the human population, it may

Are there healthy obese?

PubMed

Griera Borrás, José Luis; Contreras Gilbert, José

2014-01-01

It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness

PubMed Central

Stuart, Charles A.; Lee, Michelle L.; South, Mark A.; Howell, Mary E.A.; Cartwright, Brian M.; Ramsey, Michael W.; Stone, Michael H.

2016-01-01

Only half of pre-diabetic, subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pre-training characteristics favoring a positive response to exercise training. Thirty non-diabetic, subjects who are obese volunteered for eight weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and GLUT4 expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pre-training baseline. PMID:27379957

Altered inflammation, paraoxonase-1 activity and HDL physicochemical properties in obese humans with and without Prader-Willi syndrome

PubMed Central

Ferretti, Gianna; Bacchetti, Tiziana; Masciangelo, Simona; Grugni, Graziano; Bicchiega, Virginia

2012-01-01

SUMMARY Prader-Willi syndrome (PWS) represents the most common form of genetic obesity. Several studies confirm that obesity is associated with inflammation, oxidative stress and impairment of antioxidant systems; however, no data are available concerning PWS subjects. We compared levels of plasma lipids and C-reactive protein (CRP) in 30 subjects of ‘normal’ weight (18.5–25 kg/m2), 15 PWS obese (>30 kg/m2) subjects and 13 body mass index (BMI)-matched obese subjects not affected by PWS. In all subjects, we evaluated the levels of lipid hydroperoxides and the activity of paraoxonase-1 (PON1), an enzyme involved in the antioxidant and anti-inflammatory properties exerted by high-density lipoproteins (HDLs). Furthermore, using the fluorescent molecule of Laurdan, we investigated the physicochemical properties of HDLs isolated from normal weight and obese individuals. Altogether, our results demonstrated, for the first time, higher levels of lipid hydroperoxides and a lower PON1 activity in plasma of obese individuals with PWS with respect to normal-weight controls. These alterations are related to CRP levels, with a lower PON1:CRP ratio in PWS compared with non-PWS obese subjects. The study of Laurdan fluorescence parameters showed significant modifications of physicochemical properties in HDLs from PWS individuals. Whatever the cause of obesity, the increase of adiposity is associated with inflammation, oxidative stress and alterations in HDL compositional and functional properties. PMID:22822045

Plasma galanin concentrations in obese, normal weight and anorectic women.

PubMed

Invitti, C; Brunani, A; Pasqualinotto, L; Dubini, A; Bendinelli, P; Maroni, P; Cavagnini, F

1995-05-01

Galanin is believed to play a role in the control of eating behavior. No information is available on its concentrations in the biological fluids in human obesity, and this study aimed to clarify this. We measured plasma galanin and serum insulin levels in 30 obese, 35 normal weight and 11 anorectic women. Mean galanin values were quite similar in obese and control subjects (76.8 +/- 3.20 vs 76.1 +/- 2.33 pg/ml) and only slightly reduced in anorectic patients (67.9 +/- 2.30 pg/ml). Insulin levels were significantly increased and decreased in obese and anorectic patients, respectively, compared to controls. Insulin correlated positively with BMI in the whole group of subjects studied (r = 0.72, P < 0.0001) and in the obese subgroup (r = 0.56, P < 0.02). No correlations could be detected between WH ratio, insulin and galanin concentrations and between galanin and BMI. In conclusion, plasma galanin concentrations appear to be comparable in obese, normal weight and anorectic subjects. This does not exclude a role of galanin in the regulation of eating behavior since variations of the peptide in discrete brain areas may not be detectable in general circulation and peripheral sources of the peptide may contribute to its plasma levels. Also, our data suggest that galanin does not play a major role in the regulation of insulin secretion in humans.

Hunter-Gatherer Energetics and Human Obesity

PubMed Central

Pontzer, Herman; Raichlen, David A.; Wood, Brian M.; Mabulla, Audax Z. P.; Racette, Susan B.; Marlowe, Frank W.

2012-01-01

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg−1 m−1) and resting (kcal kg−1 s−1) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences. PMID:22848382

Obesity induction in hamster that mimics the human clinical condition.

PubMed

Jordania da Silva, Vivian; Dias, Sílvia Regina Costa; Maioli, Tatiani Uceli; Serafim, Luciana Ribeiro; Furtado, Luis Fernando Viana; Quintão Silva, Maria da Gloria; Faria, Ana Maria Caetano de; Rabelo, Élida Mara Leite

2017-08-05

Although obesity is well established in hamsters, studies using diets with high levels of simple carbohydrate associated with lipids are necessary to assess the impact of this type of food in the body. In this study a high sugar and butter diet (HSB) and high temperature were employed towards this end. Obesity was successfully induced at a temperature of 30.3°C to 30.9°C after 38 days feeding the animals an HSB diet. It was shown that although diet is important for the induction of obesity, temperature is also essential because at a temperature slightly below the one required, obesity was not induced, even when the animals were fed for a longer period (150 days).The obese clinical condition was accompanied by biochemical and hematological changes, as increased cholesterol and triglyceride levels and increased leukocyte numbers, similar to alterations observed in obese humans. Furthermore, it was demonstrated that increasing the intake of simple carbohydrates associated with lipids provided evidence of inflammation in obese animals.

Obesity induction in hamster that mimics the human clinical condition

PubMed Central

Jordania da Silva, Vivian; Dias, Sílvia Regina Costa; Maioli, Tatiani Uceli; Serafim, Luciana Ribeiro; Furtado, Luis Fernando Viana; Quintão Silva, Maria da Gloria; de Faria, Ana Maria Caetano; Rabelo, Élida Mara Leite

2017-01-01

Although obesity is well established in hamsters, studies using diets with high levels of simple carbohydrate associated with lipids are necessary to assess the impact of this type of food in the body. In this study a high sugar and butter diet (HSB) and high temperature were employed towards this end. Obesity was successfully induced at a temperature of 30.3°C to 30.9°C after 38 days feeding the animals an HSB diet. It was shown that although diet is important for the induction of obesity, temperature is also essential because at a temperature slightly below the one required, obesity was not induced, even when the animals were fed for a longer period (150 days).The obese clinical condition was accompanied by biochemical and hematological changes, as increased cholesterol and triglyceride levels and increased leukocyte numbers, similar to alterations observed in obese humans. Furthermore, it was demonstrated that increasing the intake of simple carbohydrates associated with lipids provided evidence of inflammation in obese animals. PMID:28367889

Changes in gallbladder bile composition and crystal detection time in morbidly obese subjects after bariatric surgery.

PubMed

Gustafsson, Ulf; Benthin, Lisbet; Granström, Lars; Groen, Albert K; Sahlin, Staffan; Einarsson, Curt

2005-06-01

The aim of the present study was to elucidate the mechanisms of development of cholesterol crystals and gallstones during weight reduction in obese subjects. Twenty-five morbidly obese, gallstone-free subjects underwent vertical-banded gastroplasty. Gallbladder bile was collected at the time of the operation via needle aspiration and 1.1-7.3 months after the operation via ultrasound-guided transhepatic puncture of the gallbladder. The mean weight loss was 17 kg. Two patients developed gallstones and 10 patients displayed cholesterol crystals in their bile. In patients with a follow-up time of less than 2 months (n = 13), cholesterol saturation increased from 90% to 114% but tended to decrease in the patients with a follow-up time of more than 2 months. The extraction of the concanavalin-A-binding fraction from gallbladder bile obtained after weight reduction in 7 patients prolonged crystallization detection time from 6 to 10 days. The hexosamine concentration, a marker for mucin, was increased by about 100% in bile obtained in 6 of 7 patients after weight reduction. In conclusion, the results indicate that crystallization-promoting compounds (mucin) are of great importance in the development of cholesterol crystals and gallstones in obese subjects during weight reduction, probably because of defective gallbladder emptying.

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

Fatty Liver Index Associates with Relative Sarcopenia and GH/ IGF- 1 Status in Obese Subjects

PubMed Central

Gnessi, Lucio; Mariani, Stefania; Lenzi, Andrea; Donini, Lorenzo Maria

2016-01-01

Introduction Recently the association between hepatic steatosis and sarcopenia has been described. GH/IGF-1 axis has been postulated to play a role in linking fatty liver and low muscle mass. The aim of our study was to explore the association between fatty liver index, sarcopenic obesity, insulin sensitivity, and GH/IGF-1 status. Methods 427 subjects [age: 45.65±13.94 years, BMI: 36.92±6.43 kg/m2] were enrolled. Participants were divided into three groups: fatty liver index (FLI) <20, 20≥FLI<60, and FLI≥60. Body composition was assessed by DXA. The truncal fat mass (TrFM) to appendicular skeletal muscle (ASM) ratio was used as an indicator of sarcopenic obesity. ISI-Matsuda index was used. Results BMI, fat mass, and the TrFM/ASM ratio were higher in subjects with FLI≥60. GH, IGF-1 and ISI-Matsuda were lower in the high FLI group (all p<0.05). A significantly positive correlation between FLI and TrFM/ ASM ratio (r = 0.221, p<0.001) was found, whereas FLI levels were negatively correlated with ISI- Matsuda (r = -0.335, p<0.001), GH (r = -0.200, p = 0.006), and IGF- 1 levels (r = -0.157, p = 0.028). Stepwise linear regression analysis showed that GH levels were significantly negatively correlated with FLI, while the TrFM/ ASM ratio was positively associated with FLI, after adjustment for age, BMI, total fat mass, truncal fat mass, fat- free mass, and ISI- Matsuda. Conclusions Impairment of GH/IGF-1 axis seems to be associated to the risk of the development of sarcopenic obesity and ectopic fat deposition in the liver. Metabolic and hormonal derangements as determinants of ectopic fat deposition and body composition deserve to be evaluated in obese subjects. PMID:26741958

Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human.

PubMed

Tremblay-Franco, Marie; Zerbinati, Chiara; Pacelli, Antonio; Palmaccio, Giuseppina; Lubrano, Carla; Ducheix, Simon; Guillou, Hervé; Iuliano, Luigi

2015-07-01

Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human. In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids. 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection. We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis. Our data provide the first evidence that obesity and metabolic syndrome are associated with

Minireview: Epigenetics of Obesity and Diabetes in Humans

PubMed Central

Slomko, Howard; Heo, Hye J.

2012-01-01

Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation. PMID:22253427

Screening for type 2 diabetes mellitus in overweight and obese subjects made easy by the FINDRISC score.

PubMed

Meijnikman, A S; De Block, C E M; Verrijken, A; Mertens, I; Corthouts, B; Van Gaal, L F

2016-08-01

To evaluate the use of the FINDRISC score in an overweight and obese population to predict glucose status. In 651 overweight/obese subjects (M/F: 193/458, age 43±13 y, BMI 38.2±6.1kg/m(2)) glucose status was tested using OGTT and HbA1c. Furthermore, the FINDRISC questionnaire and CT visceral fat (VAT) and subcutaneous fat (SAT) were examined. Exactly 50.4% were found to have prediabetes and 11.1% were newly diagnosed with type 2 diabetes (T2DM) (M/F=22.2/8.8%). Subjects without T2DM had a FINDRISC score of 11±3, those with pre-DM 13±4, and subjects with de novo T2DM 15±5. The aROC of the FINDRISC for detecting T2DM was 0.76 (95% CI 0.72-0.82), with 13 as cutoff point. The FINDRISC score correlated with VAT (r=0.34, p<0.001) and VAT/SAT ratio (r=0.39, p<0.001). The aROC of the FINDRISC to detect excess VAT was 0.79 (95%CI 0.72-0.84). In a large group of overweight and obese subjects, 50.4% were found to have pre-DM and 11.1% were newly diagnosed with T2DM. The FINDRISC score increased with worsening of glucose tolerance status and proved to be an independent predictor of T2DM status, as did HOMA-B, HOMA-S and VAT. The FINDRISC can also function as a good tool to predict visceral obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Peptide YY: a potential therapy for obesity.

PubMed

Renshaw, D; Batterham, R L

2005-03-01

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.

Leptin reverses declines in satiation in weight-reduced obese humans123

PubMed Central

Kissileff, Harry R; Thornton, John C; Torres, Migdalia I; Pavlovich, Katherine; Mayer, Laurel S; Kalari, Vamsi; Leibel, Rudolph L

2012-01-01

Background: Individuals who are weight-reduced or leptin deficient have a lower energy expenditure coupled with higher hunger and disinhibition and/or delayed satiation compared with never-weight-reduced control subjects. Because exogenous leptin inhibits feeding in congenitally leptin-deficient humans, reduced leptin signaling may reduce the expression of feeding inhibition in humans. Objective: The objective was to test the hypothesis that reduced leptin signaling may reduce the expression of feeding inhibition (ie, blunt satiation) in humans by examining the effects of leptin repletion on feeding behavior after weight loss. Design: Ten obese humans (4 men, 6 women) were studied as inpatients while they received a weight-maintaining liquid-formula diet. Satiation was studied by measuring intake and ratings of appetite-related dispositions 3 h after ingestion of 300 kcal of the liquid-formula diet. The subjects were studied at each of 3 time periods: 1) while they maintained their usual weight (Wtinitial) and then after weight reduction and stabilization at 10% below initial weight and while they received 5 wk of either 2) twice-daily injections of placebo (Wt-10%placebo) or 3) “replacement doses” of leptin (Wt-10%leptin) in a single-blind crossover design with a 2-wk washout period between treatments. Energy expenditure was also measured at each study period. Results: Both energy expenditure and visual analog scale ratings that reflect satiation were significantly lower at Wt-10%placebo than at Wtinitial and Wt-10%leptin. Conclusion: The results are consistent with the hypothesis that the absence of leptin signaling after weight loss may blunt the expression of feeding inhibition in humans. PMID:22237063

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...

A PYY Q62P variant linked to human obesity

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

Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy

2005-06-27

Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysismore » of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.« less

Mechanical external work and recovery at preferred walking speed in obese subjects.

PubMed

Malatesta, Davide; Vismara, Luca; Menegoni, Francesco; Galli, Manuela; Romei, Marianna; Capodaglio, Paolo

2009-02-01

The aim of this study was to compare the mechanical external work (per kg) and pendular energy transduction at preferred walking speed (PWS) in obese versus normal body mass subjects to investigate whether obese adults adopt energy conserving gait mechanics. The mechanical external work (Wext) and the fraction of mechanical energy recovered by the pendular mechanism (Rstep) were computed using kinematic data acquired by an optoelectronic system and were compared in 30 obese (OG; body mass index [BMI] = 39.6 +/- 0.6 kg m(-2); 29.5 +/- 1.3 yr) and 19 normal body mass adults (NG; BMI = 21.4 +/- 0.5 kg m(-2); 31.2 +/- 1.2 yr) walking at PWS. PWS was significantly lower in OG (1.18 +/- 0.02 m s(-1)) than in NG (1.33 +/- 0.02 m s(-1); P Obese adults do not appear to alter their gait to improve pendular energy transduction and may select slower PWS to reduce mechanical and metabolic work.

Lipid Partitioning, Incomplete Fatty Acid Oxidation, and Insulin Signal Transduction in Primary Human Muscle Cells: Effects of Severe Obesity, Fatty Acid Incubation, and Fatty Acid Translocase/CD36 Overexpression

PubMed Central

Bell, Jill A.; Reed, Melissa A.; Consitt, Leslie A.; Martin, Ola J.; Haynie, Kimberly R.; Hulver, Matthew W.; Muoio, Deborah M.; Dohm, G. Lynis

2010-01-01

Context: Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance. Objective: To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes. Design, Setting, and Patients: Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women. To emulate the obesity phenotype in our cell culture system, we incubated cells from lean individuals with excess FA or overexpressed FAT/CD36 using recombinant adenoviral technology. Results: Complete oxidation of FA was significantly reduced, whereas total lipid accumulation, FA esterification into lipid intermediates, and incomplete oxidation were up-regulated in the muscle cells of severely obese subjects. Insulin signal transduction was reduced in the muscle cells from severely obese subjects compared to lean controls. Incubation of muscle cells from lean subjects with lipids reduced insulin signal transduction and increased lipid storage and incomplete FA oxidation. CD36 overexpression increased FA transport capacity, but did not impair complete FA oxidation and insulin signal transduction in muscle cells from lean subjects. Conclusions: Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter. PMID:20427507

Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

PubMed Central

Lackey, Denise E.; Lynch, Christopher J.; Olson, Kristine C.; Mostaedi, Rouzbeh; Ali, Mohamed; Smith, William H.; Karpe, Fredrik; Humphreys, Sandy; Bedinger, Daniel H.; Dunn, Tamara N.; Thomas, Anthony P.; Oort, Pieter J.; Kieffer, Dorothy A.; Amin, Rajesh; Bettaieb, Ahmed; Haj, Fawaz G.; Permana, Paska; Anthony, Tracy G.

2013-01-01

Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35–50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals. PMID:23512805

SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus.

PubMed

Hassing, H Carlijne; Surendran, R Preethi; Derudas, Bruno; Verrijken, An; Francque, Sven M; Mooij, Hans L; Bernelot Moens, Sophie J; Hart, Leen M 't; Nijpels, Giel; Dekker, Jacqueline M; Williams, Kevin Jon; Stroes, Erik S G; Van Gaal, Luc F; Staels, Bart; Nieuwdorp, Max; Dallinga-Thie, Geesje M

2014-05-01

Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM. Copyright © 2013 The Obesity Society.

Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.

PubMed

Butler, Merlin G; McGuire, Austen; Manzardo, Ann M

2015-04-01

Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form. We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions. By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution

Neprilysin, obesity and the metabolic syndrome

PubMed Central

Standeven, Kristina F.; Hess, Katharina; Carter, Angela M.; Rice, Gillian I.; Cordell, Paul A.; Balmforth, Anthony J.; Lu, Bao; Scott, D. Julian; Turner, Anthony J.; Hooper, Nigel M.; Grant, Peter J.

2010-01-01

Objective Neprilysin (NEP), a zinc metallo-endopeptidase, has a role in blood pressure control and lipid metabolism. The present study tested the hypothesis that NEP is associated with insulin resistance and features of the metabolic syndrome (MetS) in a study of 318 healthy human subjects and in murine obesity and investigated NEP production by adipocytes in-vitro. Methods and Results In 318 white European males, plasma NEP was elevated in the MetS and increased progressively with increasing MetS components. Plasma NEP activity correlated with insulin, homeostasis model assessment and body mass index in all subjects (p<0.01). Quantitative RT-PCR and Western blotting showed that in human pre-adipocytes NEP expression is upregulated 25-30 fold during differentiation into adipocytes. Microarray analysis of mRNA from differentiated human adipocytes confirmed high NEP expression comparable to adiponectin and plasminogen activator inhibitor-1. In a murine model of diet-induced insulin resistance, plasma NEP levels were significantly higher in high fat diet (HFD)-fed compared with normal chow diet (NCD)-fed animals (1642±529 and 820±487 pg/μl, respectively; p<0.01). Tissue NEP was increased in mesenteric fat in HFD compared with NCD-fed mice (p<0.05). NEP knock out mice did not display any changes in insulin resistance, glucose tolerance or body and epididymal fat pad weight compared to wild type mice. Conclusions In humans, NEP activity correlated with body mass index and measures of insulin resistance with increasing levels in subjects with multiple cardiovascular risk factors. NEP protein production in human adipocytes increased during cell differentiation and plasma and adipose tissue levels of NEP were increased in obese insulin resistant mice. Our results indicate that NEP associates with cardio-metabolic risk in the presence of insulin resistance and increases in obesity. PMID:21042321

Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

PubMed

Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

2017-07-01

Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (P<.05) in AO-HPIR than that in AO-LPIR and controls. Postprandial triglycerides AUC was higher (P<.05), whereas high-density lipoprotein cholesterol AUC was lower (P<.05), in AO-HPIR than those in AO-LPIR and controls. Postprandial AUCs for total cholesterol and apolipoprotein B were similar in abdominally obese subjects with different degrees of postprandial insulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in taste sensitivity between obese and non-obese children and adolescents.

PubMed

Overberg, Johanna; Hummel, Thomas; Krude, Heiko; Wiegand, Susanna

2012-12-01

Taste sensitivity varies between individuals. Several studies describe differences between obese and non-obese subjects concerning their taste perception. However, data are partly contradictory and insufficient. Therefore, in this study taste sensitivity of obese and non-obese children/adolescents was analysed. In a cross-sectional study gustatory sensitivity of n=99 obese subjects (body mass index (BMI) >97th percentile) and n=94 normal weight subjects (BMI <90th percentile), 6-18 years of age, was compared. Sensitivity for the taste qualities sweet, sour, salty, umami and bitter was analysed by means of impregnated 'taste strips' in different concentrations. A total score was determined for all taste qualities combined as well as for each separately. Furthermore, the possible influence of sex, age and ethnicity on taste perception was analysed. An intensity rating for sweet was performed on a 5-point rating scale. Obese subjects showed-compared to the control group-a significantly lower ability to identify the correct taste qualities regarding the total score (p<0.001). Regarding individual taste qualities there was a significantly lower detection rate for salty, umami and bitter by obese subjects. Furthermore, the determinants age and sex had a significant influence on taste perception: older age and female sex was associated with better ability to identify taste qualities. Concerning the sweet intensity rating obese children gave significantly lower intensity ratings to three of the four concentrations. Obese and non-obese children and adolescents differ in their taste perception. Obese subjects could identify taste qualities less precisely than children and adolescents of normal weight.

The role of gut microbiota in human obesity: recent findings and future perspectives.

PubMed

Tagliabue, A; Elli, M

2013-03-01

In recent years, gut microbiota have gained a growing interest as an environmental factor that may affect the predisposition toward adiposity. In this review, we describe and discuss the research that has focused on the involvement of gut microbiota in human obesity. We also summarize the current knowledge concerning the health effects of the composition of gut microbiota, acquired using the most recent methodological approaches, and the potential influence of gut microbiota on adiposity, as revealed by animal studies. Original research studies that were published in English or French until December 2011 were selected through a computer-assisted literature search. The studies conducted to date show that there are differences in the gut microbiota between obese and normal-weight experimental animals. There is also evidence that a high-fat diet may induce changes in gut microbiota in animal models regardless of the presence of obesity. In humans, obesity has been associated with reduced bacterial diversity and an altered representation of bacterial species, but the identified differences are not homogeneous among the studies. The question remains as to whether changes in the intestinal microbial community are one of the environmental causes of overweight and obesity or if they are a consequence of obesity, specifically of the unbalanced diet that often accompanies the development of excess weight gain. In the future, larger studies on the potential role of intestinal microbiota in human obesity should be conducted at the species level using standardized analytical techniques and taking all of the possible confounding variables into account. Copyright © 2012 Elsevier B.V. All rights reserved.

Three-dimensional surface imaging system for assessing human obesity

NASA Astrophysics Data System (ADS)

Xu, Bugao; Yu, Wurong; Yao, Ming; Pepper, M. Reese; Freeland-Graves, Jeanne H.

2009-10-01

The increasing prevalence of obesity suggests a need to develop a convenient, reliable, and economical tool for assessment of this condition. Three-dimensional (3-D) body surface imaging has emerged as an exciting technology for the estimation of body composition. We present a new 3-D body imaging system, which is designed for enhanced portability, affordability, and functionality. In this system, stereo vision technology is used to satisfy the requirement for a simple hardware setup and fast image acquisition. The portability of the system is created via a two-stand configuration, and the accuracy of body volume measurements is improved by customizing stereo matching and surface reconstruction algorithms that target specific problems in 3-D body imaging. Body measurement functions dedicated to body composition assessment also are developed. The overall performance of the system is evaluated in human subjects by comparison to other conventional anthropometric methods, as well as air displacement plethysmography, for body fat assessment.

SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus

PubMed Central

Hassing, H. Carlijne; Surendran, R. Preethi; Derudas, Bruno; Verrijken, An; Francque, Sven M.; Mooij, Hans L.; Bernelot Moens, Sophie J.; ’t Hart, Leen M.; Nijpels, Giel; Dekker, Jacqueline M.; Williams, Kevin Jon; Stroes, Erik S. G.; Van Gaal, Luc F.; Staels, Bart; Nieuwdorp, Max; Dallinga-Thie, Geesje M.

2014-01-01

Objective Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodelling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here we sought to investigate the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM. Design and Methods Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Results Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; p=0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (p<0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P<0.05) and retinyl esters (RE) levels (P<0.001). Conclusions These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM. PMID:24339435

45 CFR 63.31 - Protection of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Protection of human subjects. 63.31 Section 63.31 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED... Protection of human subjects. All grants made pursuant to this part are subject to the specific provisions of...

45 CFR 63.31 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Protection of human subjects. 63.31 Section 63.31 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED... Protection of human subjects. All grants made pursuant to this part are subject to the specific provisions of...

45 CFR 63.31 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Protection of human subjects. 63.31 Section 63.31 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED... Protection of human subjects. All grants made pursuant to this part are subject to the specific provisions of...

45 CFR 63.31 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Protection of human subjects. 63.31 Section 63.31 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED... Protection of human subjects. All grants made pursuant to this part are subject to the specific provisions of...

45 CFR 63.31 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Protection of human subjects. 63.31 Section 63.31 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED... Protection of human subjects. All grants made pursuant to this part are subject to the specific provisions of...

34 CFR 76.681 - Protection of human subjects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Protection of human subjects. 76.681 Section 76.681 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must... of human subjects. If a State or a subgrantee uses a human subject in a research project, the State...

34 CFR 76.681 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Protection of human subjects. 76.681 Section 76.681 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must... of human subjects. If a State or a subgrantee uses a human subject in a research project, the State...

34 CFR 76.681 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Protection of human subjects. 76.681 Section 76.681 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must... of human subjects. If a State or a subgrantee uses a human subject in a research project, the State...

34 CFR 76.681 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false Protection of human subjects. 76.681 Section 76.681 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must... of human subjects. If a State or a subgrantee uses a human subject in a research project, the State...

34 CFR 76.681 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Protection of human subjects. 76.681 Section 76.681 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must... of human subjects. If a State or a subgrantee uses a human subject in a research project, the State...

Food insecurity as a driver of obesity in humans: The insurance hypothesis.

PubMed

Nettle, Daniel; Andrews, Clare; Bateson, Melissa

2017-01-01

Integrative explanations of why obesity is more prevalent in some sectors of the human population than others are lacking. Here, we outline and evaluate one candidate explanation, the insurance hypothesis (IH). The IH is rooted in adaptive evolutionary thinking: The function of storing fat is to provide a buffer against shortfall in the food supply. Thus, individuals should store more fat when they receive cues that access to food is uncertain. Applied to humans, this implies that an important proximate driver of obesity should be food insecurity rather than food abundance per se. We integrate several distinct lines of theory and evidence that bear on this hypothesis. We present a theoretical model that shows it is optimal to store more fat when food access is uncertain, and we review the experimental literature from non-human animals showing that fat reserves increase when access to food is restricted. We provide a meta-analysis of 125 epidemiological studies of the association between perceived food insecurity and high body weight in humans. There is a robust positive association, but it is restricted to adult women in high-income countries. We explore why this could be in light of the IH and our theoretical model. We conclude that although the IH alone cannot explain the distribution of obesity in the human population, it may represent a very important component of a pluralistic explanation. We also discuss insights it may offer into the developmental origins of obesity, dieting-induced weight gain, and anorexia nervosa.

Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

PubMed

Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

2017-09-01

Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

Brain iron overload, insulin resistance, and cognitive performance in obese subjects: a preliminary MRI case-control study.

PubMed

Blasco, Gerard; Puig, Josep; Daunis-I-Estadella, Josep; Molina, Xavier; Xifra, Gemma; Fernández-Aranda, Fernando; Pedraza, Salvador; Ricart, Wifredo; Portero-Otín, Manuel; Fernández-Real, José Manuel

2014-11-01

The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects. We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 ± 7.7 years; BMI 43.7 ± 4.48 kg/m2) and 20 healthy nonobese volunteers (10 women; age 48.8 ± 9.5 years; BMI 24.3 ± 3.54 kg/m2) in whom iron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance. A significant increase in iron load was detected at the caudate nucleus (P < 0.001), lenticular nucleus (P = 0.004), hypothalamus (P = 0.002), hippocampus (P < 0.001), and liver (P < 0.001) in obese subjects. There was a positive correlation between HIC and BIO at caudate (r = 0.517, P < 0.001), hypothalamus (r = 0.396, P = 0.009), and hippocampus (r = 0.347, P < 0.023). The area under the curve of insulin was independently associated with BIO at the caudate (P = 0.001), hippocampus (P = 0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P = 0.006), and lenticular nucleus (P = 0.012) were independently associated with worse cognitive performance. Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction. © 2014 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.

Association of overweight and obesity with interest in healthy eating, subjective health and perceived risk of chronic diseases in three European countries.

PubMed

Pieniak, Zuzanna; Pérez-Cueto, Federico; Verbeke, Wim

2009-12-01

This paper analyses cultural differences in consumers' interest in healthy eating, subjective health and perceived risk of (chronic) diseases, and identifies the association between nutritional status (obesity and overweight) and the above mentioned variables as well as people's socio-demographic characteristics and health conditions that may influence food choice. Cross-sectional data were collected through a consumer survey (n=2400) in 2008 with samples representative for age and region in France, Poland and Spain. Body-mass-index (BMI) was inversely associated with education and positively associated with age. Women were less likely to be overweight than men. Subjective health was negatively associated with the likelihood of being obese. The likelihood of being obese decreased with higher perceived risk of suffering from stress and from cancer, whilst the likelihood of being overweight decreased with higher perceived risk of suffering from stress. Despite a tendency of lower interest in healthy eating among obese consumers, interest in healthy eating was not significantly associated with the likelihood of being obese or overweight after Holm-Bonferroni correction. The findings of this study suggest that health consequences and disease risks of excessive weight should be better communicated to European populations. Furthermore, factors associated with obesity such as subjective health and perceived risk of chronic diseases should be considered both at individual counselling and at public health policy levels.

A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian subjects but not in patients with coronary heart disease.

PubMed

Sustar, A; Nikolac Perkovic, M; Nedic Erjavec, G; Svob Strac, D; Pivac, N

2016-08-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with an important role in the regulation of body weight, body mass index (BMI) and obesity. Increased BMI that leads to obesity is a substantial risk factor for coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265) has been associated with CHD, obesity and BMI. The aim of the study was to determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in patients with CHD and healthy control subjects. The study included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control subjects. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more

Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds.

PubMed

Cirera, S; Jensen, M S; Elbrønd, V S; Moesgaard, S G; Christoffersen, B Ø; Kadarmideen, H N; Skovgaard, K; Bruun, C V; Karlskov-Mortensen, P; Jørgensen, C B; Fredholm, M

2014-02-01

Obesity has reached epidemic proportions globally and has become the cause of several major health risks worldwide. Presently, more than 100 loci have been related to obesity and metabolic traits in humans by genome-wide association studies. The complex genetic architecture behind obesity has triggered a need for the development of better animal models than rodents. The pig has emerged as a very promising biomedical model to study human obesity traits. In this study, we have characterized the expression patterns of six obesity-related genes, leptin (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), fat mass and obesity associated (FTO), neuronal growth regulator 1 (NEGR)1 and adiponectin (ADIPOQ), in seven obesity-relevant tissues (liver; muscle; pancreas; hypothalamus; and retroperitoneal, subcutaneous and mesenteric adipose tissues) in two pig breeds (production pigs and Göttingen minipigs) that deviate phenotypically and genetically from each other with respect to obesity traits. We observe significant differential expression for LEP, LEPR and ADIPOQ in muscle and in all three adipose tissues. Interestingly, in pancreas, LEP expression is only detected in the fat minipigs. FTO shows significant differential expression in all tissues analyzed, and NEGR1 shows significant differential expression in muscle, pancreas, hypothalamus and subcutaneous adipose tissue. The MC4R transcript can be detected only in hypothalamus. In general, the expression profiles of the investigated genes are in accordance with those observed in human studies. Our study shows that both the differences between the investigated breeds and the phenotypic state with respect to obesity/leanness play a large role for differential expression of the obesity-related genes. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Factors associated with early atherosclerosis and arterial calcifications in young subjects with a benign phenotype of obesity.

PubMed

Gilardini, Luisa; Pasqualinotto, Lucia; Di Matteo, Silvia; Caffetto, Katherine; Croci, Marina; Girola, Andrea; Invitti, Cecilia

2011-08-01

We assessed (i) the association between early arterial disease and factors linked to adiposity, dietary habits, and family in a young cohort of 151 obese children and adolescents with less than or equal to one cardiovascular (CV) risk factor, (ii) whether in subjects with carotid calcifications there was an imbalance of calcium-phosphorus homeostasis. Measurement included: carotid ultrasound, oral glucose tolerance test, anthropometry, body composition, dietary history, white blood cells count, lipids, uric acid, adiponectin, insulin, C-reactive protein, plasminogen activator inhibitor 1 (PAI-1), 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium and phosphorus. Obese children with carotid artery intima media thickness (cIMT) values >75° percentile (0.55 mm), compared to those with lower cIMT, were more obese, more often pubertal and had higher prevalence of family history of CV disease (CVD) (P < 0.05), higher plasma PAI-1 and uric acid (P < 0.001) and lower adiponectin (P < 0.05) and high-density lipoprotein (HDL) cholesterol levels (P < 0.05). After adjustment for sex, age, puberty, obesity, and insulin levels, only PAI-I remained significantly different between the two groups (10.9 (7.2-29.8) vs. 6.2 (4.3-10.6) ng/ml, P < 0.001). Dietary intake did not affect cIMT values. Eight percent of subjects showed nonatherosclerotic carotid calcifications with patchy pattern. These children had a worse lipid profile (P < 0.05) and higher plasma PTH levels (48.6 ± 21.5 vs 38.5 ± 16.9 pg/ml, P < 0.05) that were inversely associated with 25-hydroxyvitamin D levels (r = 0.245, P < 0.01). Present results suggest that (i) several adiposity-related factors may play a role in promoting the development of early arterial diseases in young subjects with a benign phenotype of obesity, (ii) a PTH rise resulting from a subclinical imbalance in calcium-phosphorus homeostasis may affect the biological process of vascular calcifications.

[Role of probiotics in obesity management].

PubMed

Prados-Bo, Andreu; Gómez-Martínez, Sonia; Nova, Esther; Marcos, Ascensión

2015-02-07

Obesity is a major public health issue as it is related to several chronic disorders, including type-2 diabetes, high blood pressure, dyslipemia, cardiovascular diseases and cancer, among others. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, it has been observed in germ-free mice that transplantation of the microbiota of either obese or lean mice influences body weight, suggesting that the gut ecosystem is a relevant target for weight management. Certain strains of probiotics may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. Taken together, our knowledge about the influence of gut microbiota on obesity is progressing. Therefore, modulation of its composition through probiotics may provide new opportunities to manage overweight and obesity. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Economic Growth, Climate Change, and Obesity.

PubMed

Minos, Dimitrios; Butzlaff, Iris; Demmler, Kathrin Maria; Rischke, Ramona

2016-12-01

Human and planetary health as well as economic growth are firmly interlinked and subject to complex interaction effects. In this paper, we provide an overview of interlinkages between economic growth, climate change, and obesity focusing on recent advances in the literature. In addition to empirical findings, we discuss different theoretical frameworks used to conceptualize these complex links and highlight policy options and challenges. We conclude that policies addressing both climate change and obesity simultaneously are particularly promising and often suitable for ensuring sustainable development.

48 CFR 1552.223-70 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Protection of human... 1552.223-70 Protection of human subjects. As prescribed in 1523.303-70, insert the following contract clause when the contract involves human test subjects. Protection of Human Subjects (APR 1984) (a) The...

48 CFR 1552.223-70 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Protection of human... 1552.223-70 Protection of human subjects. As prescribed in 1523.303-70, insert the following contract clause when the contract involves human test subjects. Protection of Human Subjects (APR 1984) (a) The...

48 CFR 1552.223-70 - Protection of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Protection of human... 1552.223-70 Protection of human subjects. As prescribed in 1523.303-70, insert the following contract clause when the contract involves human test subjects. Protection of Human Subjects (APR 1984) (a) The...

48 CFR 1552.223-70 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Protection of human... 1552.223-70 Protection of human subjects. As prescribed in 1523.303-70, insert the following contract clause when the contract involves human test subjects. Protection of Human Subjects (APR 1984) (a) The...

48 CFR 1552.223-70 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Protection of human... 1552.223-70 Protection of human subjects. As prescribed in 1523.303-70, insert the following contract clause when the contract involves human test subjects. Protection of Human Subjects (APR 1984) (a) The...

Metabolic thrift and the genetic basis of human obesity

PubMed Central

O’Rourke, Robert W.

2014-01-01

Evolution has molded metabolic thrift within humans, a genetic heritage that, when thrust into our modern “obesogenic” environment, creates the current obesity crisis. Modern genetic analysis has identified genetic and epigenetic contributors to obesity, an understanding of which will guide the development of environmental, pharmacologic, and genetic therapeutic interventions. “The voyage was so long, food and water ran out. One hundred of the paddlers died; forty men remained. The voyagers finally reached Fitinui, then Aotona.”-From “The Story of Aka”, in The Native Culture in the Marquesas by E. S. Craighill Handy PMID:24368636

Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

PubMed

Kras, Katon A; Hoffman, Nyssa; Roust, Lori R; Patel, Shivam H; Carroll, Chad C; Katsanos, Christos S

2017-12-01

Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals. To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults. Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions. Eligible participants were healthy lean (body mass index, <25 kg/m2; age, 37 ± 3 years; n = 10) and obese (body mass index >30 kg/m2; age 35 ± 3 years; n = 11) subjects. Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions. Mitochondrial respiration and ATP production. AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P < 0.05), but not obese, subjects. Furthermore, AA infusion increased the uncoupled (i.e., non-ADP-stimulated) respiration of SS mitochondria in the lean subjects only (P < 0.05). AA infusion had no effect on any of these parameters in IMF mitochondria in either lean or obese subjects (P > 0.05). Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals. Copyright © 2017 Endocrine Society

Maintenance of weight loss or stability in subjects with obesity: a retrospective longitudinal analysis of a real-world population.

PubMed

DerSarkissian, Maral; Bhak, Rachel H; Huang, Joanna; Buchs, Sarah; Vekeman, Francis; Smolarz, B Gabriel; Brett, Jason; Ganguly, Rahul; Duh, Mei Sheng

2017-06-01

Characterize patterns of weight change among subjects with obesity. A retrospective observational longitudinal study of subjects with obesity was conducted using the General Electric Centricity electronic medical record database. Subjects who were ≥18 years old with BMI ≥30 kg/m 2 (first defining index BMI), had no medical conditions associated with unintentional weight loss, and had ≥4 BMI measurements/year for ≥2.5 years were included and categorized into groups (stable weight: within <5% of index BMI; modest weight loss: ≥5 to <10% of index BMI lost; moderate weight loss: ≥10 to <15% of index BMI lost; and high weight loss: ≥15% of index BMI lost) based on weight change during 6 months following index. No interventions were considered. Patterns of weight change were then assessed for 2 years. A total of 177,743 subjects were included: 85.1% of subjects were in the stable weight, 9.3% in the modest, 2.3% in the moderate, and 3.3% in the high weight loss groups. The proportion of subjects who maintained or continued to lose weight decreased over the 2 year observation period; 11% of those with high weight loss continued to lose weight and 19% maintained their weight loss. This group had the lowest percentage of subjects who regained ≥50% of lost weight and the lowest proportion of subjects with weight cycling (defined as not continuously losing, gaining, or maintaining weight throughout the 2 year observation period relative to its beginning). This trend persisted in subgroups with class II-III obesity, pre-diabetes, and type 2 diabetes. Weight cycling and regain were commonly observed. Subjects losing the most weight during the initial period were more likely to continue losing weight.

Human chorionic gonadotropin (HCG) treatment of obesity.

PubMed

Shetty, K R; Kalkhoff, R K

1977-02-01

After a nine-day control period, six hospitalized obese women were placed on 500 calorie diets and were given 125 IU of human chorionic gonadotropin (HCG) intramuscularly daily for 30 days. Another five obese women received injections of diluent only and consumed identical diets for the same period. Mean weight loss in the HCG-treated group was nearly identical to that achieved by women given the placebo. Reduction of triceps skinfold thickness or circumferential body measurements of the chest, waist, hips, and thighs were not different. Patters of change of a variety of plasma and urine substrates, electrolytes, and hormones were similar in the two groups and consistent with semistarvation and weight loss. These results indicate that HCG has no effects on chemical and hormonal parameters measured and offers no advantage over calorie restriction in promoting weight loss.

Dicarbonyl stress in clinical obesity.

PubMed

Masania, Jinit; Malczewska-Malec, Malgorzata; Razny, Urszula; Goralska, Joanna; Zdzienicka, Anna; Kiec-Wilk, Beata; Gruca, Anna; Stancel-Mozwillo, Julita; Dembinska-Kiec, Aldona; Rabbani, Naila; Thornalley, Paul J

2016-08-01

The glyoxalase system in the cytoplasm of cells provides the primary defence against glycation by methylglyoxal catalysing its metabolism to D-lactate. Methylglyoxal is the precursor of the major quantitative advanced glycation endproducts in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. Glyoxalase 1 of the glyoxalase system was linked to anthropometric measurements of obesity in human subjects and to body weight in strains of mice. Recent conference reports described increased weight gain on high fat diet-fed mouse with lifelong deficiency of glyoxalase 1 deficiency, compared to wild-type controls, and decreased weight gain in glyoxalase 1-overexpressing transgenic mice, suggesting a functional role of glyoxalase 1 and dicarbonyl stress in obesity. Increased methylglyoxal, dicarbonyl stress, in white adipose tissue and liver may be a mediator of obesity and insulin resistance and thereby a risk factor for development of type 2 diabetes and non-alcoholic fatty liver disease. Increased methylglyoxal formation from glyceroneogenesis on adipose tissue and liver and decreased glyoxalase 1 activity in obesity likely drives dicarbonyl stress in white adipose tissue increasing the dicarbonyl proteome and related dysfunction. The clinical significance will likely emerge from on-going clinical evaluation of inducers of glyoxalase 1 expression in overweight and obese subjects. Increased transcapillary escape rate of albumin and increased total body interstitial fluid volume in obesity likely makes levels of glycation of plasma protein unreliable indicators of glycation status in obesity as there is a shift of albumin dwell time from plasma to interstitial fluid, which decreases overall glycation for a given glycemic exposure.

Pharmacokinetics of ceftaroline in normal body weight and obese (classes I, II, and III) healthy adult subjects.

PubMed

Justo, Julie Ann; Mayer, Stockton M; Pai, Manjunath P; Soriano, Melinda M; Danziger, Larry H; Novak, Richard M; Rodvold, Keith A

2015-07-01

The pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m(2) and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m(2) compared to those <30 kg/m(2). A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 μg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Three-point Dixon method enables whole-body water and fat imaging of obese subjects.

PubMed

Berglund, Johan; Johansson, Lars; Ahlström, Håkan; Kullberg, Joel

2010-06-01

Dixon imaging techniques derive chemical shift-separated water and fat images, enabling the quantification of fat content and forming an alternative to fat suppression. Whole-body Dixon imaging is of interest in studies of obesity and the metabolic syndrome, and possibly in oncology. A three-point Dixon method is proposed where two solutions are found analytically in each voxel. The true solution is identified by a multiseed three-dimensional region-growing scheme with a dynamic path, allowing confident regions to be solved before unconfident regions, such as background noise. 2 pi-Phase unwrapping is not required. Whole-body datasets (256 x 184 x 252 voxels) were collected from 39 subjects (body mass index 19.8-45.4 kg/m(2)), in a mean scan time of 5 min 15 sec. Water and fat images were reconstructed offline, using the proposed method and two reference methods. The resulting images were subjectively graded on a four-grade scale by two radiologists, blinded to the method used. The proposed method was found superior to the reference methods. It exclusively received the two highest grades, implying that only mild reconstruction failures were found. The computation time for a whole-body dataset was 1 min 51.5 sec +/- 3.0 sec. It was concluded that whole-body water and fat imaging is feasible even for obese subjects, using the proposed method. (c) 2010 Wiley-Liss, Inc.

Disability, Physical Inactivity, and Impaired Health-Related Quality of Life Are Not Different in Metabolically Healthy vs. Unhealthy Obese Subjects

PubMed Central

Donini, Lorenzo M.; Merola, Gianluca; Poggiogalle, Eleonora; Lubrano, Carla; Gnessi, Lucio; Mariani, Stefania; Migliaccio, Silvia; Lenzi, Andrea

2016-01-01

Background: Obesity represents a major health hazard, affecting morbidity, psychological status, physical functionality, quality of life, and mortality. The aim of the present study was to explore the differences between metabolically healthy (MHO) and metabolically unhealthy (MUO) obese subjects with regard to physical activity, disability, and health-related quality of life (HR-QoL). Methods: All subjects underwent a multidimensional evaluation, encompassing the assessment of body composition, metabolic biomarkers and inflammation, physical activity level (IPAQ questionnaire), disability (TSD-OC test), and HR-QoL (SF-36 questionnaire). MHO and MUO were defined based on the absence or the presence of the metabolic syndrome, respectively. Results: 253 subjects were included (54 men and 199 women; age: 51.7 ± 12.8 vs. 50.3 ± 11.7 years, p = 0.46; BMI: 38.1 ± 5.7 vs. 38.9 ± 6.7 kg/m2, p = 0.37). No significant difference was observed in body composition. There was no difference between MHO and MUO considering inflammation (hs-CRP: 6517.1 ± 11,409.9 vs. 5294.1 ± 5612.2 g/L; p = 0.37), physical inactivity (IPAQ score below 3000 METs-min/week in 77.6% of MHO vs. 80% of MUO subjects; p = 0.36), obesity-related disability (TSD-OC score > 33%, indicating a high level of obesity-related disability, in 20.2% of MHO vs. 26.5% of MUO subjects; p = 0.28), and the HR-QoL (SF-36 total score: 60 ± 20.8 vs. 62.8 ± 18.2, p = 0.27). Discussion and Conclusion: The metabolic comorbidity and the impairment of functional ability and psycho-social functioning may have a different timing in the natural history of obesity. Alterations in the physical activity level and mobility disabilities may precede the onset of metabolic abnormalities. (Trial registration 2369 prot 166/12—registered 23 February 2012; Amendment 223/14—registered 13 February 2014). PMID:27897994

Disability, Physical Inactivity, and Impaired Health-Related Quality of Life Are Not Different in Metabolically Healthy vs. Unhealthy Obese Subjects.

PubMed

Donini, Lorenzo M; Merola, Gianluca; Poggiogalle, Eleonora; Lubrano, Carla; Gnessi, Lucio; Mariani, Stefania; Migliaccio, Silvia; Lenzi, Andrea

2016-11-25

Obesity represents a major health hazard, affecting morbidity, psychological status, physical functionality, quality of life, and mortality. The aim of the present study was to explore the differences between metabolically healthy (MHO) and metabolically unhealthy (MUO) obese subjects with regard to physical activity, disability, and health-related quality of life (HR-QoL). All subjects underwent a multidimensional evaluation, encompassing the assessment of body composition, metabolic biomarkers and inflammation, physical activity level (IPAQ questionnaire), disability (TSD-OC test), and HR-QoL (SF-36 questionnaire). MHO and MUO were defined based on the absence or the presence of the metabolic syndrome, respectively. 253 subjects were included (54 men and 199 women; age: 51.7 ± 12.8 vs. 50.3 ± 11.7 years, p = 0.46; BMI: 38.1 ± 5.7 vs. 38.9 ± 6.7 kg/m², p = 0.37). No significant difference was observed in body composition. There was no difference between MHO and MUO considering inflammation (hs-CRP: 6517.1 ± 11,409.9 vs. 5294.1 ± 5612.2 g/L; p = 0.37), physical inactivity (IPAQ score below 3000 METs-min/week in 77.6% of MHO vs. 80% of MUO subjects; p = 0.36), obesity-related disability (TSD-OC score > 33%, indicating a high level of obesity-related disability, in 20.2% of MHO vs. 26.5% of MUO subjects; p = 0.28), and the HR-QoL (SF-36 total score: 60 ± 20.8 vs. 62.8 ± 18.2, p = 0.27). The metabolic comorbidity and the impairment of functional ability and psycho-social functioning may have a different timing in the natural history of obesity. Alterations in the physical activity level and mobility disabilities may precede the onset of metabolic abnormalities. (Trial registration 2369 prot 166/12-registered 23 February 2012; Amendment 223/14-registered 13 February 2014).

Employment discrimination against obese women in obesity clinic's patients perspective.

PubMed

Obara-Gołębiowska, Małgorzata

2016-01-01

The workplace is one of many areas of life where obese people are unfairly treated. According to the literature obese women are particularly susceptible to discrimination in employment. There is a lack of polish researches of this subject. The main objective of this study was to analyze personal, subjective experiences related to weight bias and discrimination against obese people in the workplace of obese Polish women. The study was carried out in a hospital clinic for obesity management. A total of 420 women with BMI>30, aged 21 to 72, participated in group interviews focused on the weight bias and discrimination against obese people in the workplace. In the group of clinically obese women, 5.3% of subjects had experienced employment discrimination and 10.5% had been victims of verbal and social abuse in the workplace. The most common psycho-physical consequences of the weight stigma were emotional problems, lack of motivation and overeating in response to stress. Weight-based discrimination in the workplace poses a problem in Poland. The weight stigma and occupational discrimination lead to psycho-physical discomfort which exacerbates overeating and obesity.

Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects

PubMed Central

Stelmach-Mardas, Marta; Mardas, Marcin; Warchoł, Wojciech; Jamka, Małgorzata; Walkowiak, Jarosław

2014-01-01

The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat. PMID:25311271

Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects.

PubMed

Stelmach-Mardas, Marta; Mardas, Marcin; Warchoł, Wojciech; Jamka, Małgorzata; Walkowiak, Jarosław

2014-10-14

The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat.

Nutritional ecology of obesity: from humans to companion animals.

PubMed

Raubenheimer, David; Machovsky-Capuska, Gabriel E; Gosby, Alison K; Simpson, Stephen

2015-01-01

We apply nutritional geometry, a framework for modelling the interactive effects of nutrients on animals, to help understand the role of modern environments in the obesity pandemic. Evidence suggests that humans regulate the intake of protein energy (PE) more strongly than non-protein energy (nPE), and consequently will over- and under-ingest nPE on diets with low or high PE, respectively. This pattern of macronutrient regulation has led to the protein leverage hypothesis, which proposes that the rise in obesity has been caused partly by a shift towards diets with reduced PE:nPE ratios relative to the set point for protein regulation. We discuss potential causes of this mismatch, including environmentally induced reductions in the protein density of the human diet and factors that might increase the regulatory set point for protein and hence exacerbate protein leverage. Economics--the high price of protein compared with fats and carbohydrates--is one factor that might contribute to the reduction of dietary protein concentrations. The possibility that rising atmospheric CO₂ levels could also play a role through reducing the PE:nPE ratios in plants and animals in the human food chain is discussed. Factors that reduce protein efficiency, for example by increasing the use of ingested amino acids in energy metabolism (hepatic gluconeogenesis), are highlighted as potential drivers of increased set points for protein regulation. We recommend that a similar approach is taken to understand the rise of obesity in other species, and identify some key gaps in the understanding of nutrient regulation in companion animals.

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.

Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans

PubMed Central

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

2017-01-01

Background 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. Objectives 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. Methods 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. Results 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. PMID:29236751

Urinary cortisol and psychopathology in obese binge eating subjects.

PubMed

Lavagnino, Luca; Amianto, Federico; Parasiliti Caprino, Mirko; Maccario, Mauro; Arvat, Emanuela; Ghigo, Ezio; Abbate Daga, Giovanni; Fassino, Secondo

2014-12-01

Investigations on the relationship between obesity, binge eating and the function of hypothalamic-pituitary-adrenal (HPA) axis have led to inconsistent results. General psychopathology affects HPA axis function. The present study aims to examine correlations between binge eating, general psychopathology and HPA axis function in obese binge eaters. Twenty-four hour urinary free cortisol (UFC/24 h) was measured in 71 obese binge eating women. The patients were administered psychometric tests investigating binge eating, psychopathology and clinical variables. The relationship between binge eating, psychopathology and urinary cortisol was investigated, controlling for age and BMI. We found an inverse correlation between UFC/24 h and binge eating, depression, obsessive-compusive symptoms, somatization and sensitivity. In a regression model a significant inverse correlation between urinary cortisol and psychopathology was confirmed. Urinary cortisol levels in obese patients with binge eating disorder show an inverse correlation with several dimensions of psychopathology which are considered to be typical of a cluster of psychiatric disorders characterized by low HPA axis function, and are very common in obese binge eating patients. If these results are confirmed, UFC/24 h might be considered a biomarker of psychopathology in obese binge eaters. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up.

PubMed

Aksungar, F B; Sarıkaya, M; Coskun, A; Serteser, M; Unsal, I

2017-01-01

Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance. Single-arm Interventional Human Study. 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years). Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month. While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence

PubMed Central

Harvie, Michelle; Howell, Anthony

2017-01-01

Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation. PMID:28106818

Clinical implications of gait analysis in the rehabilitation of adult patients with "Prader-Willi" Syndrome: a cross-sectional comparative study ("Prader-Willi" Syndrome vs matched obese patients and healthy subjects).

PubMed

Vismara, Luca; Romei, Marianna; Galli, Manuela; Montesano, Angelo; Baccalaro, Gabriele; Crivellini, Marcello; Grugni, Graziano

2007-05-10

Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). PWS is a complex multisystem disorder, representing the most common form of genetic obesity. The aim of this study was the analysis of the gait pattern of adult subjects with PWS by using three-Dimensional Gait Analysis. The results were compared with those obtained in a group of obese patients and in a group of healthy subjects. Cross-sectional, comparative study: 19 patients with PWS (11 males and 8 females, age: 18-40 years, BMI: 29.3-50.3 kg/m2); 14 obese matched patients (5 males and 9 females, age: 18-40 years, BMI: 34.3-45.2 kg/m2); 20 healthy subjects (10 males and 10 females, age: 21-41 years, BMI: 19.3-25.4 kg/m2). Kinematic and kinetic parameters during walking were assessed by an optoelectronic system and two force platforms. PWS adult patients walked slower, had a shorter stride length, a lower cadence and a longer stance phase compared with both matched obese, and healthy subjects. Obese matched patients showed spatio-temporal parameters significantly different from healthy subjects.Furthermore, Range Of Motion (ROM) at knee and ankle, and plantaflexor activity of PWS patients were significantly different between obese and healthy subjects. Obese subjects revealed kinematic and kinetic data similar to healthy subjects. PWS subjects had a gait pattern significantly different from obese patients. Despite that, both groups had a similar BMI. We suggest that PWS gait abnormalities may be related to abnormalities in the development of motor skills in childhood, due to precocious obesity. A tailored rehabilitation program in early childhood of PWS patients could prevent gait pattern changes.

Clinical implications of gait analysis in the rehabilitation of adult patients with "Prader-Willi" Syndrome: a cross-sectional comparative study ("Prader-Willi" Syndrome vs matched obese patients and healthy subjects)

PubMed Central

Vismara, Luca; Romei, Marianna; Galli, Manuela; Montesano, Angelo; Baccalaro, Gabriele; Crivellini, Marcello; Grugni, Graziano

2007-01-01

Background Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). PWS is a complex multisystem disorder, representing the most common form of genetic obesity. The aim of this study was the analysis of the gait pattern of adult subjects with PWS by using three-Dimensional Gait Analysis. The results were compared with those obtained in a group of obese patients and in a group of healthy subjects. Methods Cross-sectional, comparative study: 19 patients with PWS (11 males and 8 females, age: 18–40 years, BMI: 29.3–50.3 kg/m2); 14 obese matched patients (5 males and 9 females, age: 18–40 years, BMI: 34.3–45.2 kg/m2); 20 healthy subjects (10 males and 10 females, age: 21–41 years, BMI: 19.3–25.4 kg/m2). Kinematic and kinetic parameters during walking were assessed by an optoelectronic system and two force platforms. Results PWS adult patients walked slower, had a shorter stride length, a lower cadence and a longer stance phase compared with both matched obese, and healthy subjects. Obese matched patients showed spatio-temporal parameters significantly different from healthy subjects. Furthermore, Range Of Motion (ROM) at knee and ankle, and plantaflexor activity of PWS patients were significantly different between obese and healthy subjects. Obese subjects revealed kinematic and kinetic data similar to healthy subjects. Conclusion PWS subjects had a gait pattern significantly different from obese patients. Despite that, both groups had a similar BMI. We suggest that PWS gait abnormalities may be related to abnormalities in the development of motor skills in childhood, due to precocious obesity. A tailored rehabilitation program in early childhood of PWS patients could prevent gait pattern changes. PMID:17493259

Interaction of dietary fat intake with APOA2, APOA5 and LEPR polymorphisms and its relationship with obesity and dyslipidemia in young subjects.

PubMed

Domínguez-Reyes, Teresa; Astudillo-López, Constanza C; Salgado-Goytia, Lorenzo; Muñoz-Valle, José F; Salgado-Bernabé, Aralia B; Guzmán-Guzmán, Iris P; Castro-Alarcón, Natividad; Moreno-Godínez, Ma E; Parra-Rojas, Isela

2015-09-13

Diet is an important environmental factor that interacts with genes to modulate the likelihood of developing disorders in lipid metabolism and the relationship between diet and genes in the presence of other chronic diseases such as obesity. The objective of this study was to analyze the interaction of a high fat diet with the APOA2 (rs3813627 and rs5082), APOA5 (rs662799 and rs3135506) and LEPR (rs8179183 and rs1137101) polymorphisms and its relationship with obesity and dyslipidemia in young subjects. The study included 200 young subjects aged 18 to 25 years (100 normal-weight and 100 obese subjects). Dietary fat intake was measured using the frequency food consumption questionnaire. Genotyping of polymorphisms was performed by PCR-RFLP. Individuals carrying the APOA5 56 G/G genotype with a high saturated fatty acid consumption (OR = 2.7, p = 0.006) and/or total fat (OR = 2.4, p = 0.018), associated with an increased risk of obesity. We also found that A/G + G/G genotypes of the 668 A/G polymorphism in the LEPR gene with an intake ≥ 12 g/d of saturated fatty acids, have 2.9 times higher risk of obesity (p = 0.002), 3.8 times higher risk of hypercholesterolemia (p = 0.002) and 2.4 times higher risk of hypertriglyceridemia (p = 0.02), than those with an intake <12 g/d of saturated fatty acids. Similarly, LEPR 668 A/G + G/G carriers with a high fat total intake had 3.0 times higher risk of obesity (p = 0.002) and 4.1 times higher risk of hypercholesterolemia (p = 0.001). Our results suggest that dietary fat intake modifies the effect of APOA5 and LEPR polymorphisms on serum triglycerides, cholesterol levels and obesity in young subjects.

An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2.

PubMed

Kim, Jaemin; Lee, Taeheon; Kim, Tae-Hun; Lee, Kyung-Tai; Kim, Heebal

2012-12-19

Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa), may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity. We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05) and type 2 diabetes (P = 0.00578). Through the estimation of variance of genetic component (heritability) for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479) between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15) was most important in explaining the phenotypic variance for obesity. Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B.

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.

PubMed

Wang, Gene-Jack; Yang, Julia; Volkow, Nora D; Telang, Frank; Ma, Yeming; Zhu, Wei; Wong, Christopher T; Tomasi, Dardo; Thanos, Panayotis K; Fowler, Joanna S

2006-10-17

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively.

Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome.

PubMed

Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel; Lykkegaard, Kirsten; Tang-Christensen, Mads; Hansen, Harald S; Levin, Barry E; Larsen, Philip Just; Knudsen, Lotte Bjerre; Fosgerau, Keld; Vrang, Niels

2010-09-01

The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia, hyperinsulinemia, and dyslipidemia, and showed a worsening of glucose tolerance over time. In line with the hyperlipidemic profile, a severe hepatic fat infiltration was observed in DIO rats at 6 months of age. The effects of liraglutide and sibutramine were tested in 6-month-old DIO rats. Both compounds effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents.

Very low calorie diet without aspartame in obese subjects: improved metabolic control after 4 weeks treatment.

PubMed

Norén, Erik; Forssell, Henrik

2014-07-28

Very low calorie diet (VLCD) is routinely used in programs for treatment of obesity and before bariatric surgery in order to reduce risk of postoperative complications. Aspartame, an artificial sweetener, is commonly used in VLCD and is well approved as a food additive without any adverse effects. The development of a new fructose containing VLCD formula without aspartame raises questions as to effects on glucose and lipid control. As part of an ongoing study of a novel bariatric surgery procedure, twenty-five obese subjects with mean body mass index (BMI) 39.8 kg/m2 and mean age of 48.8 years enrolled in a single center observational study. Seven subjects presented with type 2 diabetes mellitus. The subjects underwent four weeks dietary treatment with VLCD Slanka (Slanka). Blood samples including fasting plasma glucose, HbA1c, cholesterol and triglycerides were performed at start and after four weeks of diet. Blood pressure and weight were noted. All subjects completed the diet without any adverse events. Mean weight reduction was 8.2 kg with 95% confidence interval 7.1-9.2 kg (p = 0.001). Excess weight (i.e. proportion of weight exceeding BMI 25) loss decreased by median 19.5% (inter quartile range (IQR) 16,8-24,2). Median fasting plasma glucose was at inclusion 5,6 mmol/l (IQR 5,3-6,8) and after diet 4.8 mmol/l (IQR 4,6-5,2) (p = 0.001). Median HbA1c changed from 39 mmol/mol (IQR 37-44) to 37 mmol/mol (IQR 35-43) (p = 0.001). There was also significant reduction in cholesterol and triglyceride levels as well as in systolic blood pressure. Changes in other monitored blood chemistry values were without clinical importance. Four weeks treatment with fructose containing VLCD of obese subjects preparing for bariatric surgery gave a substantial weight reduction without any significant negative metabolic effects.

Very low calorie diet without aspartame in obese subjects: improved metabolic control after 4 weeks treatment

PubMed Central

2014-01-01

Background Very low calorie diet (VLCD) is routinely used in programs for treatment of obesity and before bariatric surgery in order to reduce risk of postoperative complications. Aspartame, an artificial sweetener, is commonly used in VLCD and is well approved as a food additive without any adverse effects. The development of a new fructose containing VLCD formula without aspartame raises questions as to effects on glucose and lipid control. Methods As part of an ongoing study of a novel bariatric surgery procedure, twenty-five obese subjects with mean body mass index (BMI) 39.8 kg/m2 and mean age of 48.8 years enrolled in a single center observational study. Seven subjects presented with type 2 diabetes mellitus. The subjects underwent four weeks dietary treatment with VLCD Slanka (Slanka®). Blood samples including fasting plasma glucose, HbA1c, cholesterol and triglycerides were performed at start and after four weeks of diet. Blood pressure and weight were noted. Results All subjects completed the diet without any adverse events. Mean weight reduction was 8.2 kg with 95% confidence interval 7.1–9.2 kg (p = 0.001). Excess weight (i.e. proportion of weight exceeding BMI 25) loss decreased by median 19.5% (inter quartile range (IQR) 16,8-24,2). Median fasting plasma glucose was at inclusion 5,6 mmol/l (IQR 5,3-6,8) and after diet 4.8 mmol/l (IQR 4,6-5,2) (p = 0.001). Median HbA1c changed from 39 mmol/mol (IQR 37–44) to 37 mmol/mol (IQR 35–43) (p = 0.001). There was also significant reduction in cholesterol and triglyceride levels as well as in systolic blood pressure. Changes in other monitored blood chemistry values were without clinical importance. Conclusion Four weeks treatment with fructose containing VLCD of obese subjects preparing for bariatric surgery gave a substantial weight reduction without any significant negative metabolic effects. PMID:25069603

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

Diaphragm activity in obesity

PubMed Central

Lourenço, Ruy V.

1969-01-01

Diaphragm activity during carbon dioxide breathing and total chest compliance during diaphragm relaxation were measured in eight obese subjects: four with normal blood gases and four with hypercapnia and hypoxemia. Whereas there were no significant differences in the values of total chest compliance between the two groups, there were marked differences in diaphragm activity. The increase in integrated electrical activity in the diaphragm, per millimeter increment in carbon dioxide tension in the arterial blood, averaged 66 units (range: 48-90) in the obese-normal subjects and 17 units (range: 12-22) in the obese-hypoventilation subjects. These results suggest that an incapacity to increase the activity in the respiratory muscles, to levels necessary to overcome the load caused by obesity, plays a major role in the genesis of respiratory failure in obese subjects. PMID:5822573

A 3D surface imaging system for assessing human obesity

NASA Astrophysics Data System (ADS)

Xu, B.; Yu, W.; Yao, M.; Yao, X.; Li, Q.; Pepper, M. R.; Freeland-Graves, J. H.

2009-08-01

The increasing prevalence of obesity suggests a need to develop a convenient, reliable and economical tool for assessment of this condition. Three-dimensional (3D) body surface imaging has emerged as an exciting technology for estimation of body composition. This paper presents a new 3D body imaging system, which was designed for enhanced portability, affordability, and functionality. In this system, stereo vision technology was used to satisfy the requirements for a simple hardware setup and fast image acquisitions. The portability of the system was created via a two-stand configuration, and the accuracy of body volume measurements was improved by customizing stereo matching and surface reconstruction algorithms that target specific problems in 3D body imaging. Body measurement functions dedicated to body composition assessment also were developed. The overall performance of the system was evaluated in human subjects by comparison to other conventional anthropometric methods, as well as air displacement plethysmography, for body fat assessment.

Effect of Aerobic Exercise Training on Ventilatory Efficiency and Respiratory Drive in Obese Subjects.

PubMed

Chlif, Mehdi; Chaouachi, Anis; Ahmaidi, Said

2017-07-01

Obese patients show a decline in exercise capacity and diverse degrees of dyspnea in association with mechanical abnormalities, increased ventilatory requirements secondary to the increased metabolic load, and a greater work of breathing. Consequently, obese patients may be particularly predisposed to the development of respiratory muscle fatigue during exercise. The aim of this study was to assess inspiratory muscle performance during incremental exercise in 19 obese male subjects (body mass index 41 ± 6 kg/m 2 ) after aerobic exercise training using the noninvasive, inspiratory muscle tension-time index (T T0.1 ). Measurements performed included anthropometric parameters, lung function assessed by spirometry, rate of perceived breathlessness with the modified Borg dyspnea scale (0-10), breathing pattern, maximal exercise capacity, and inspiratory muscle performance with a breath-by-breath automated exercise metabolic system during an incremental exercise test. T T0.1 was calculated using the equation, T T0.1 = P 0.1 /P Imax × T I /T tot (where P 0.1 represents mouth occlusion pressure, P Imax is maximal inspiratory pressure, and T I /T tot is the duty cycle). At rest, there was no statistically significant difference for spirometric parameters and cardiorespiratory parameters between pre- and post-training. At maximal exercise, the minute ventilation, the rate of exchange ratio, the rate of perceived breathlessness, and the respiratory muscle performance parameters were not significantly different pre- and post-training; in contrast, tidal volume ( P = .037, effect size = 1.51), breathing frequency ( P = .049, effect size = 0.97), power output ( P = .048, effect size = 0.79), peak oxygen uptake ( P = .02, effect size = 0.92) were significantly higher after training. At comparable work load, training induces lower minute ventilation, mouth occlusion pressure, ratio of occlusion pressure to maximal inspiratory pressure, T T0.1 , and rate of perceived

Validation of the Italian version of the Laval questionnaire: health-related quality of life in subjects with obesity.

PubMed

Donini, Lorenzo Maria; Rosano, Aldo; Di Lazzaro, Luca; Poggiogalle, Eleonora; Lubrano, Carla; Migliaccio, Silvia; Carbonelli, Mariagrazia; Pinto, Alessandro; Lenzi, Andrea

2017-05-15

Obesity is associated to increased risk of metabolic comorbidity as well as increased mortality. Notably, obesity is also associated to the impairment of the psychological status and of quality of life. Only three questionnaires are available in the Italian language evaluating the health-related quality of life in subjects with obesity. The aim of the present study was to test the validity and reliability of the Italian version of the Laval Questionnaire. The original French version was translated into Italian and back-translated by a French native speaker. 273 subjects with obesity (Body Mass Index ≥ 30 kg/m 2 ) were enrolled; the Italian version of the Laval Questionnaire and the O.R.Well-97 questionnaire were administered in order to assess health- related quality of life. The Laval questionnaire consists of 44 items distributed in 6 domains (symptoms, activity/mobility, personal hygiene/clothing, emotions, social interaction, sexual life). Disability and overall psychopathology levels were assessed through the TSD-OC test (SIO test for obesity correlated disabilities) and the SCL-90 (Symptom Checklist-90) questionnaire, respectively. To verify the validity of the Italian version, the analysis of internal consistency, test-retest reliability, and construct validity were performed. The observed proportion of agreement concordance of results was 50.2% with Cohen's K = 0.336 (CI 95%: 0.267-0.404), indicating a fair agreement between the two tests. Test-retest correlation was statistically significant (ρ = 0.82; p < 0.01); validity (standardized Chronbach's alpha) was considered reliable (α > 0.70). The analysis of construct validity showed a statistically significant association in terms of both total score (ρ = -0.66) and scores at each single domain (p < 0.01). A high correlation (p < 0.01) was observed between Laval questionnaire total and single domain scores and other related measures (Body Mass Index, TSD-OC scores, SCL

48 CFR 3424.170 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Protection of human... Individual Privacy 3424.170 Protection of human subjects. In this subsection, “Research” means a systematic... generalizable knowledge. (34 CFR 97.102(d)) Research is considered to involve human subjects when a researcher...

48 CFR 3424.170 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Protection of human... Individual Privacy 3424.170 Protection of human subjects. In this subsection, “Research” means a systematic... generalizable knowledge. (34 CFR 97.102(d)) Research is considered to involve human subjects when a researcher...

48 CFR 3424.170 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Protection of human... Individual Privacy 3424.170 Protection of human subjects. In this subsection, “Research” means a systematic... generalizable knowledge. (34 CFR 97.102(d)) Research is considered to involve human subjects when a researcher...

48 CFR 3424.170 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Protection of human... Individual Privacy 3424.170 Protection of human subjects. In this subsection, “Research” means a systematic... generalizable knowledge. (34 CFR 97.102(d)) Research is considered to involve human subjects when a researcher...

Environmental Perturbations: Obesity

PubMed Central

Shore, Stephanie A.

2014-01-01

Obesity currently affects about one third of the U.S. population, while another one third is overweight. The importance of obesity for certain conditions such as heart disease and type 2 diabetes is well appreciated. The effects of obesity on the respiratory system have received less attention and are the subject of this chapter. Obesity alters the static mechanic properties of the respiratory system leading to a reduction in the functional residual capacity (FRC) and the expiratory reserve volume (ERV). There is substantial variability in the effects of obesity on FRC and ERV, at least some of which is related to the location, rather than the total mass of adipose tissue. Obesity also results in airflow obstruction, which is only partially attributable to breathing at low lung volume, and can also promote airway hyperresponsiveness and asthma. Hypoxemia is common is obesity, and correlates well with FRC, as well as with measures of abdominal obesity. However, obese subjects are usually eucapnic, indicating that hypoventilation is not a common cause of their hypoxemia. Instead, hypoxemia results from ventilation perfusion mismatch caused by closure of dependent airways at FRC. Many obese subjects complain of dyspnea either at rest or during exertion, and the dyspnea score also correlates with reductions in FRC and ERV. Weight reduction should be encouraged in any symptomatic obese individual, since virtually all of the respiratory complications of obesity improve with even moderate weight loss. PMID:23737172

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects

PubMed Central

Gosmanov, Aidar R.; Smiley, Dawn D.; Peng, Limin; Siquiera, Joselita; Robalino, Gonzalo; Newton, Christopher; Umpierrez, Guillermo E.

2013-01-01

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022), and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone. PMID:22483976

[Factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome].

PubMed

Gu, C J; Li, Q Y; Li, M; Zhou, J; Du, J; Yi, H H; Feng, J; Zhou, L N; Wang, Q

2016-05-17

To explore the factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 106 young obese subjects[18-44 years old, body mass index (BMI) ≥30 kg/m(2)]were enrolled and divided into two groups based on full-night polysomnography (PSG), OSAHS group[apnea hypopnea index (AHI) ≥5 events/h]and non-OSAHS group (AHI<5 events/h). Oral glucose tolerance-insulin releasing test (OGTT-IRT) was performed and serum glycosylated hemoglobin A1 (HbA1c) levels were measured after an overnight fast. Homeostasis model assessment-IR (HOMA-IR), Matsuda insulin sensitivity index (MI), homeostasis model assessment-β (HOMA-β), the early phase insulinogenic index (ΔI(30)/ΔG(30)), total area under the curve of insulin in 180 minutes (AUC-I180) and oral disposition index (DIo) were calculated to evaluate insulin resistance and pancreatic β cell function. Stepwise multiple linear regressions were conducted to determine the independent linear correlation of glucose measurements with PSG parameters. Prevalence of diabetes was higher in OSAHS than in non-OSAHS group (22.0% vs 4.3%, P=0.009). OGTT 0, 30, 60 min glucose and HbA1c levels were higher in OSAHS group than those in non-OASHS group (all P<0.05). DIo were lower in OSAHS group than those in non-OASHS group (P=0.024), HOMA-IR, MI, HOMA-β, ΔI(30)/ΔG(30), and AUC-I(180) were similar between two groups (all P>0.05). In stepwise multiple linear regressions, OGTT 0, 30 and 60 min glucose were positively correlated with oxygen desaturation index (ODI) (β=0.243, 0.273 and 0.371 respectively, all P<0.05). HOMA-β was negatively correlated with AHI (β=-0.243, P=0.011). DIo was negatively correlated with ODI (β=-0.234, P=0.031). OSAHS worsens glucose metabolism and compensatory pancreatic β-cell function in young obese subjects, which could probably be attributed to sleep apnea related oxygen desaturation during sleep.

Gly972Arg variant of insulin receptor substrate 1 gene and colorectal cancer risk in overweight/obese subjects.

PubMed

Mahmoudi, Touraj; Majidzadeh-A, Keivan; Karimi, Khatoon; Farahani, Hamid; Dabiri, Reza; Nobakht, Hossein; Asadi, Asadollah; Karimi, Negar; Arkani, Maral; Zali, Mohammad Reza

2016-02-28

Given the major role of obesity and insulin resistance (IR) in colorectal cancer (CRC), we investigated whether genetic variants in ghrelin (GHRL), resistin (RETN) and insulin receptor substrate 1 (IRS1) were associated with CRC risk. This study was conducted as a case-control study, and 750 subjects, including 438 controls and 312 patients with CRC, were enrolled and genotyped using the PCR-RFLP method. No significant differences were observed for GHRL (rs696217), RETN (rs3745367) and IRS1 (rs1801278, Gly972Arg or G972R) gene variants between the cases and controls. However, the IRS1 G972R R allele compared with the G allele and the G972R RR+GR genotype compared with the GG genotype appeared to be markers of decreased CRC susceptibility in the overweight/obese subjects (p = 0.024; odds ratio [OR] = 0.42, 95% confidence interval [95% CI], 0.20-0.91; and p = 0.048; OR = 0.42, 95% CI, 0.17-0.99, respectively). Furthermore, the R allele and RR+GR genotype were also associated with decreased risks for obesity in the patients with CRC (p = 0.007; OR = 0.35, 95% CI, 0.15-0.77; and p = 0.015; OR = 0.35, 95% CI, 0.15-0.72, respectively). In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for CRC in overweight/obese patients and for obesity in patients with CRC. Nevertheless, further studies are required to confirm these findings.

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans

PubMed Central

Stanhope, Kimber L.; Schwarz, Jean Marc; Keim, Nancy L.; Griffen, Steven C.; Bremer, Andrew A.; Graham, James L.; Hatcher, Bonnie; Cox, Chad L.; Dyachenko, Artem; Zhang, Wei; McGahan, John P.; Seibert, Anthony; Krauss, Ronald M.; Chiu, Sally; Schaefer, Ernst J.; Ai, Masumi; Otokozawa, Seiko; Nakajima, Katsuyuki; Nakano, Takamitsu; Beysen, Carine; Hellerstein, Marc K.; Berglund, Lars; Havel, Peter J.

2009-01-01

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults. PMID:19381015

MiR-27b-3p Regulation in Browning of Human Visceral Adipose Related to Central Obesity.

PubMed

Yu, Jing; Lv, Yifan; Di, Wenjuan; Liu, Juan; Kong, Xiaocen; Sheng, Yunlu; Huang, Min; Lv, Shan; Qi, Hanmei; Gao, Mei; Liang, Hui; Kim, Sarah; Fu, Zan; Zhou, Hong; Ding, Guoxian

2018-02-01

Given the rising prevalence of central obesity and the discovery that beige cells appear within white adipose tissue, strategies to enhance these energy-expending adipocytes or "browning" within white adipose depots have become of therapeutic interest to combat obesity and its associated disorders. This study focused on, the role of microRNA (miRNA)-27b-3p in human visceral adipose tissue (VAT) browning. Expression of miR-27b-3p and UCP1 in VAT and serum of humans was measured. MiR-27b-3p was overexpressed or suppressed in human visceral stromal fraction cells to analyze the potential role of miR-27b-3p. UCP1 expression in human VAT decreased with elevated BMI and waist-hip ratio, whereas expression of miR-27b-3p was found to correlate positively with BMI and waist-hip ratio. High expression of miR-27b-3p was associated with reduced browning ability of human visceral adipocytes. Antagonism of miR-27b-3p led to the enhancement of browning ability in human visceral adipocytes. These findings highlight the decreased browning ability of VAT from humans with obesity and the role of miR-27b-3p in regulating browning of human visceral adipocytes. They suggest that miR-27b-3p should be further explored as a potential target for the treatment of central obesity. © 2017 The Obesity Society.

Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

USDA-ARS?s Scientific Manuscript database

Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum.

PubMed

De Luca, Arnaud; Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J; Ingrand, Pierre; Hankard, Régis

2016-01-01

Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period.

34 CFR 75.681 - Protection of human research subjects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Protection of human research subjects. 75.681 Section... Conditions Must Be Met by a Grantee? Other Requirements for Certain Projects § 75.681 Protection of human research subjects. If a grantee uses a human subject in a research project, the grantee shall protect the...

34 CFR 75.681 - Protection of human research subjects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false Protection of human research subjects. 75.681 Section... Conditions Must Be Met by a Grantee? Other Requirements for Certain Projects § 75.681 Protection of human research subjects. If a grantee uses a human subject in a research project, the grantee shall protect the...

34 CFR 75.681 - Protection of human research subjects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Protection of human research subjects. 75.681 Section... Conditions Must Be Met by a Grantee? Other Requirements for Certain Projects § 75.681 Protection of human research subjects. If a grantee uses a human subject in a research project, the grantee shall protect the...

34 CFR 75.681 - Protection of human research subjects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Protection of human research subjects. 75.681 Section... Conditions Must Be Met by a Grantee? Other Requirements for Certain Projects § 75.681 Protection of human research subjects. If a grantee uses a human subject in a research project, the grantee shall protect the...

Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial

PubMed Central

Meyer-Gerspach, Anne Christin; Cajacob, Lucian; Riva, Daniele; Herzog, Raphael; Drewe, Juergen; Beglinger, Christoph; Wölnerhanssen, Bettina K.

2016-01-01

Background/Objectives The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads. Subjects/Methods The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water. Results Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects. Conclusions It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance. Trial Registration ClinicalTrials.gov NCT01875575 PMID:26942445

Serum leptin is associated with metabolic syndrome in obese Mexican subjects.

PubMed

García-Jiménez, Sara; Bernal Fernández, German; Martínez Salazar, Maria Fernanda; Monroy Noyola, Antonio; Toledano Jaimes, Cairo; Meneses Acosta, Angelica; Gonzalez Maya, Leticia; Aveleyra Ojeda, Elizabeth; Terrazas Meraz, Maria A; Boll, Marie-Catherine; Sánchez-Alemán, Miguel A

2015-01-01

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including insulin resistance, dyslipidemia, high blood pressure, and abdominal adiposity. Obese patients develop leptin resistance, and an increased waist circumference (WC) due to deposition of abdominal fat. The aim of this study was to evaluate the association between circulating leptin levels and MetS among sample adult Mexican workers. A total of 204 workers aged 20-56 were evaluated. Anthropometric index, blood pressure, fasting plasma glucose, and lipid profile were measured by spectrophotometric methods. Fasting insulin and leptin were measured by inmunoenzimatic methods. Furthermore, homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. The prevalence of MetS according to the ATP-III criteria was 33.8% and leptin concentrations were 2.5 times higher in women than men. Subjects with MetS had higher levels of leptin (26.7 ± 13.7) compared with those without MetS (20.1 ± 13.9; P <0.001). Leptin increased significantly while BMI increased as well (normal 14.0 ± 8.9, overweight 22.7 ± 11.7 and obese 31.4 ± 14.6) in addition to other variables such as WC, HDL-C, insulin levels, and HOMA index. Each component of MetS was stratified by sex and submitted by linear regression with a 95% of accuracy. The 50% and 53% of the BMI is explained by the concentration of leptin in men and women, respectively (P < 0.001). This study found that leptin was associated with the MetS, especially in obesity and insulin resistance, indicating a high risk for university workers to develop hypertension, DM2, and cardiovascular disease. © 2014 Wiley Periodicals, Inc.

Imaging methods for analyzing body composition in human obesity and cardiometabolic disease.

PubMed

Seabolt, Lynn A; Welch, E Brian; Silver, Heidi J

2015-09-01

Advances in the technological qualities of imaging modalities for assessing human body composition have been stimulated by accumulating evidence that individual components of body composition have significant influences on chronic disease onset, disease progression, treatment response, and health outcomes. Importantly, imaging modalities have provided a systematic method for differentiating phenotypes of body composition that diverge from what is considered normal, that is, having low bone mass (osteopenia/osteoporosis), low muscle mass (sarcopenia), high fat mass (obesity), or high fat with low muscle mass (sarcopenic obesity). Moreover, advances over the past three decades in the sensitivity and quality of imaging not just to discern the amount and distribution of adipose and lean tissue but also to differentiate layers or depots within tissues and cells is enhancing our understanding of distinct mechanistic, metabolic, and functional roles of body composition within human phenotypes. In this review, we focus on advances in imaging technologies that show great promise for future investigation of human body composition and how they are being used to address the pandemic of obesity, metabolic syndrome, and diabetes. © 2015 New York Academy of Sciences.

Metabolic profiles and lipoprotein lipid concentrations in non-obese and obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Naidoo, C; Norman, R J; Jialal, I; Reddi, K; Joubert, S M

1990-10-01

Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.

The historical, ethical, and legal background of human-subjects research.

PubMed

Rice, Todd W

2008-10-01

The current system of human-subject-research oversight and protections has developed over the last 5 decades. The principles of conducting human research were first developed as the Nuremberg code to try Nazi war criminals. The 3 basic elements of the Nuremberg Code (voluntary informed consent, favorable risk/benefit analysis, and right to withdraw without repercussions) became the foundation for subsequent ethical codes and research regulations. In 1964 the World Medical Association released the Declaration of Helsinki, which built on the principles of the Nuremberg Code. Numerous research improprieties between 1950 and 1974 in the United States prompted Congressional deliberations about human-subject-research oversight. Congress's first legislation to protect the rights and welfare of human subjects was the National Research Act of 1974, which created the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research, which issued the Belmont Report. The Belmont Report stated 3 fundamental principles for conducting human-subjects research: respect for persons, beneficence, and justice. The Office of Human Research Protections oversees Title 45, Part 46 of the Code for Federal Regulations, which pertains to human-subjects research. That office indirectly oversees human-subjects research through local institutional review boards (IRB). Since their inception, the principles of conducting human research, IRBs, and the Code for Federal Regulations have all advanced substantially. This paper describes the history and current status of human-subjects-research regulations.

Aster spathulifolius Maxim extract reduces body weight and fat mass in obese humans.

PubMed

Cho, In-Jin; Choung, Se Young; Hwang, You-Cheol; Ahn, Kyu Jeung; Chung, Ho Yeon; Jeong, In-Kyung

2016-07-01

Aster spathulifolius Maxim (AS), a perennial herb of the genus Aster within the family Asteraceae, induced weight loss in a rat model of diet-induced obesity. We hypothesized that AS could also reduce body weight in obese humans. Therefore, we performed a randomized, double-blind, placebo-controlled clinical trial in Korea to evaluate the effect of AS extract (ASE) on body weight and fat mass and its safety in obese humans. Forty-four obese participants (body mass index [BMI], 25-30 kg/m(2)) aged ≥20 years were randomly assigned to the placebo or ASE group (700 mg/d of ASE) and were instructed to take a once-daily pill for 12 weeks. Weight, BMI, waist circumference, fat mass (measured using bioimpedance, dual-energy X-ray absorptiometry, and computed tomography), and laboratory tests were assessed at baseline and at 12 weeks. Body weight significantly decreased after 12 weeks of treatment in the ASE group (placebo vs ASE: -0.08 ± 2.11 kg vs -3.30 ± 3.15 kg, P < .05), and so did body fat mass (placebo vs ASE; bioimpedance method: -0.51 ± 1.89 kg vs -2.38 ± 2.30 kg, P < .05; dual-energy X-ray absorptiometry: 0.38 ± 1.59 kg vs -2.26 ± 2.37 kg, P < .05). Changes in lipid profiles, fasting plasma glucose, and hemoglobin A1c did not differ between the 2 groups. No drug-related adverse events were observed during the study. In conclusion, ASE significantly decreases body weight and fat mass in obese humans, suggesting that ASE may be a potential therapeutic candidate for reducing obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Protections for Subjects in Human Research with Pesticides

EPA Pesticide Factsheets

All pesticide research using human subjects must meet our strict protective standards before we would consider using them in evaluating pesticides. EPA's regulation “Protections for Subjects in Human Research” was promulgated in 2006 and amended in 2013.

Evidence in obese children: contribution of hyperlipidemia, obesity-inflammation, and insulin sensitivity.

PubMed

Chang, Chi-Jen; Jian, Deng-Yuan; Lin, Ming-Wei; Zhao, Jun-Zhi; Ho, Low-Tone; Juan, Chi-Chang

2015-01-01

Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.

Nonsurgical weight loss for extreme obesity in primary care settings: results of the Louisiana Obese Subjects Study.

PubMed

Ryan, Donna H; Johnson, William D; Myers, Valerie H; Prather, Tiffany L; McGlone, Meghan M; Rood, Jennifer; Brantley, Phillip J; Bray, George A; Gupta, Alok K; Broussard, Alan P; Barootes, Bryan G; Elkins, Brian L; Gaudin, David E; Savory, Robert L; Brock, Ricky D; Datz, Geralyn; Pothakamuri, Srininvasa R; McKnight, G Tipton; Stenlof, Kaj; Sjöström, Lars V

2010-01-25

Effective primary care practice (PCP) treatments are needed for extreme obesity. The Louisiana Obese Subjects Study (LOSS) tested whether, with brief training, PCPs could effectively implement weight loss for individuals with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 40 to 60. The LOSS, a 2-year (July 5, 2005, through January 30, 2008) randomized, controlled, "pragmatic clinical trial" trained 7 PCPs and 1 research clinic in obesity management. Primary outcome measure was year-2 percentage change from baseline weight. Volunteers (597) were screened and randomized to intensive medical intervention (IMI) (n = 200) or usual care condition (UCC) (n = 190). The UCC group had instruction in an Internet weight management program. The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less, group behavioral counseling, structured diet, and choice of pharmacotherapy (sibutramine hydrochloride, orlistat, or diethylpropion hydrochloride) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24. The mean age of participants was 47 years; 83% were women, and 75% were white. Retention rates were 51% for the IMI group and 46% for the UCC group (P = .30). After 2 years, the results were as follows: (1) among 390 randomized participants, 31% in the IMI group achieved a 5% or more weight loss and 7% achieved a 20% weight loss or more, compared with 9% and 1% of those in the UCC group. (2) The mean +/- SEM baseline observation carried forward analysis showed a weight loss of -4.9% +/- 0.8% in IMI and -0.2 +/- 0.3% in UCC. (3) Last observation carried forward analysis showed a weight loss of -8.3% +/- 0.79% for IMI, whereas UCC was -0.0% +/- 0.4%. (4) A total of 101 IMI completers lost -9.7% +/- 1.3% (-12.7 +/- 1.7 kg), whereas 89 UCC completers lost -0.4% +/- 0.7% (-0.5 +/- 0.9 kg); (P < .001 for all group differences). Many metabolic parameters improved. Primary

Is it acceptable to use animals to model obese humans? A critical discussion of two arguments against the use of animals in obesity research.

PubMed

Lund, Thomas Bøker; Sørensen, Thorkild I A; Olsson, I Anna S; Hansen, Axel Kornerup; Sandøe, Peter

2014-05-01

Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal studies of obesity's causes and therapies distract attention from preventive efforts. Drawing on both empirical data and moral reasoning, we argue that the relevant attributions of responsibility and claims about distraction are not plausible, and that, therefore, there is no reason to single out the use of animals in obesity research as especially problematic.

Exploring the relationship between α-actinin-3 deficiency and obesity in mice and humans.

PubMed

Houweling, P J; Berman, Y D; Turner, N; Quinlan, K G R; Seto, J T; Yang, N; Lek, M; Macarthur, D G; Cooney, G; North, K N

2017-07-01

Obesity is a worldwide health crisis, and the identification of genetic modifiers of weight gain is crucial in understanding this complex disorder. A common null polymorphism in the fast fiber-specific gene ACTN3 (R577X) is known to influence skeletal muscle function and metabolism. α-Actinin-3 deficiency occurs in an estimated 1.5 billion people worldwide, and results in reduced muscle strength and a shift towards a more efficient oxidative metabolism. The X-allele has undergone strong positive selection during recent human evolution, and in this study, we sought to determine whether ACTN3 genotype influences weight gain and obesity in mice and humans. An Actn3 KO mouse has been generated on two genetic backgrounds (129X1/SvJ and C57BL/6J) and fed a high-fat diet (HFD, 45% calories from fat). Anthropomorphic features (including body weight) were examined and show that Actn3 KO 129X1/SvJ mice gained less weight compared to WT. In addition, six independent human cohorts were genotyped for ACTN3 R577X (Rs1815739) and body mass index (BMI), waist-to-hip ratio-adjusted BMI (WHRadjBMI) and obesity-related traits were assessed. In humans, ACTN3 genotype alone does not contribute to alterations in BMI or obesity.

Leptin and leptin receptor-related monogenic obesity.

PubMed

Dubern, Beatrice; Clement, Karine

2012-10-01

The studies based on candidate genes and encoded proteins known to cause severe obesity in rodents, have shown that these genes also contribute to human early-onset obesity especially for those involved in the leptin pathway: the leptin (LEP) and leptin receptor (LEPR) genes. Since 1997, less than 20 individuals carrying a LEP gene mutation have been identified. Patients are mostly characterized by severe early-onset obesity with severe hyperphagia and associated phenotype such hypogonadotrophic hypogonadism, high rate of infection associated with a deficiency in T cell and abnormalities of sympathetic nerve function. Therapeutic option (subcutaneous daily injection of leptin) is available for patients with LEP deficiency. It results in weight loss, mainly of fat mass, with a major effect on reducing food intake and on other dysfunctions including immunity and induction of puberty even in adults. In LEPR deficient subjects, phenotypic similarities with the LEP-deficient subjects were noticed, especially the exhibited rapid weight gain in the first few months of life, with severe hyperphagia and the endocrine abnormalities (hypogonadotrophic hypogonadism, insufficient somatotrophic or thyreotropic secretion). Leptin treatment is useless in the LEPR deficient subjects. Factors that could possibly bypass normal leptin delivery systems are being developed but are not yet currently available for the treatment of these patients. Measurement of circulating leptin may help for the diagnosis of such obesity: it is undetectable in LEP mutation carriers or extremely elevated in LEPR mutation carriers. Thus, LEPR gene screening might be also considered in subjects with the association of severe obesity with endocrine dysfunctions such as hypogonadism and with leptin related to corpulence level. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Biology of obesity: lessons from animal models of obesity.

PubMed

Kanasaki, Keizo; Koya, Daisuke

2011-01-01

Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

Stigmatization of obese individuals by human resource professionals: an experimental study.

PubMed

Giel, Katrin E; Zipfel, Stephan; Alizadeh, Manuela; Schäffeler, Norbert; Zahn, Carmen; Wessel, Daniel; Hesse, Friedrich W; Thiel, Syra; Thiel, Ansgar

2012-07-16

Weight-related stigmatization is a public health problem. It impairs the psychological well-being of obese individuals and hinders them from adopting weight-loss behaviors. We conducted an experimental study to investigate weight stigmatization in work settings using a sample of experienced human resource (HR) professionals from a real-life employment setting. In a cross-sectional, computer-based experimental study, a volunteer sample of 127 HR professionals (age: 41.1 ± 10.9 yrs., 56% female), who regularly make career decisions about other people, evaluated individuals shown in standardized photographs regarding work-related prestige and achievements. The photographed individuals differed with respect to gender, ethnicity, and Body Mass Index (BMI). Participants underestimated the occupational prestige of obese individuals and overestimated it for normal-weight individuals. Obese people were more often disqualified from being hired and less often nominated for a supervisory position, while non-ethnic normal-weight individuals were favored. Stigmatization was most pronounced in obese females. The data suggest that HR professionals are prone to pronounced weight stigmatization, especially in women. This highlights the need for interventions targeting this stigmatization as well as stigma-management strategies for obese individuals. Weight stigmatization and its consequences needs to be a topic that is more strongly addressed in clinical obesity care.

Effects of Whole Grain Wheat Bread on Visceral Fat Obesity in Japanese Subjects: A Randomized Double-Blind Study.

PubMed

Kikuchi, Yosuke; Nozaki, Satomi; Makita, Miki; Yokozuka, Shoji; Fukudome, Shin-Ichi; Yanagisawa, Takashi; Aoe, Seiichiro

2018-04-18

Metabolic syndrome is a risk factor for cardiovascular diseases and has become increasingly common in Japan. Epidemiological studies show inverse associations between intake of whole wheat grains and metabolic syndrome, but few dietary intervention trials have investigated the effect of whole wheat grain consumption. It was investigated whether a diet in which refined wheat bread (RW diet) was substituted by whole grain wheat bread (WW diet) would reduce visceral fat obesity in Japanese subjects. A randomized double-blind placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥ 23 kg/m 2 . Subjects were randomly assigned WW (WW group) or RW diets (RW group) for 12 weeks. Blood samples and computed tomography scans were obtained every 6th week. The WW group showed decrease (-4 cm 2 ) in visceral fat area (VFA) (p < 0.05), whereas the RW group showed no significant changes. These time-dependent changes were significantly different between the groups. WW diet led to significant and safe reductions in VFA in subjects with BMI ≥ 23 kg/m 2 . WW diet may contribute to preventing visceral fat obesity.

Human Subjects Research and the Physics Classroom

NASA Astrophysics Data System (ADS)

Kubitskey, Beth W.; Thomsen, Marshall

2012-09-01

Physics Education Research is a form of social science research in that it uses human subjects. As physicists we need to be aware of the ethical and legal ramifications of performing this research, taking into account the fundamental differences between working with substances and working with people. For several decades, the federal government has regulated research involving human subjects. With current procedures, a proposal soliciting federal funds for a research project involving human subjects will be flagged by the applicants institution and checked for compliance with appropriate regulations. However, there is a large body of Physics Education Research that is not federally funded and thus may not be flagged. Nevertheless, there are ethical standards that apply to this research. This paper outlines the preliminary considerations for conducting such research.

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum

PubMed Central

Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J.; Ingrand, Pierre; Hankard, Régis

2016-01-01

Introduction Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. Objective To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. Materials and Methods This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Results Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Conclusion Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period. PMID:28005966

Targeted metabolomic analysis reveals the association between the postprandial change in palmitic acid, branched-chain amino acids and insulin resistance in young obese subjects.

PubMed

Liu, Liyan; Feng, Rennan; Guo, Fuchuan; Li, Ying; Jiao, Jundong; Sun, Changhao

2015-04-01

Obesity is the result of a positive energy balance and often leads to difficulties in maintaining normal postprandial metabolism. The changes in postprandial metabolites after an oral glucose tolerance test (OGTT) in young obese Chinese men are unclear. In this work, the aim is to investigate the complex metabolic alterations in obesity provoked by an OGTT using targeted metabolomics. We used gas chromatography-mass spectrometry and ultra high performance liquid chromatography-triple quadrupole mass spectrometry to analyze serum fatty acids, amino acids and biogenic amines profiles from 15 control and 15 obese subjects at 0, 30, 60, 90 and 120 min during an OGTT. Metabolite profiles from 30 obese subjects as independent samples were detected in order to validate the change of metabolites. There were the decreased levels of fatty acid, amino acids and biogenic amines after OGTT in obesity. At 120 min, percent change of 20 metabolites in obesity has statistical significance when comparing with the controls. The obese parameters was positively associated with changes in arginine and histidine (P<0.05) and the postprandial change in palmitic acid (PA), branched-chain amino acids (BCAAs) and phenylalanine between 1 and 120 min were positively associated with fasting insulin and HOMA-IR (all P<0.05) in the obese group. The postprandial metabolite of PA and BCAAs may play important role in the development and onset of insulin resistance in obesity. Our findings offer new insights in the complex physiological regulation of the metabolism during an OGTT in obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals.

PubMed

Iozzo, Patricia; Bucci, Marco; Roivainen, Anne; Någren, Kjell; Järvisalo, Mikko J; Kiss, Jan; Guiducci, Letizia; Fielding, Barbara; Naum, Alexandru G; Borra, Ronald; Virtanen, Kirsi; Savunen, Timo; Salvadori, Piero A; Ferrannini, Ele; Knuuti, Juhani; Nuutila, Pirjo

2010-09-01

Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings. Anesthetized pigs underwent (11)C-palmitate PET imaging during fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs were measured in arterial, portal, and hepatic venous blood. The imaging methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C-palmitate kinetic analyses were used to quantify systemic and visceral lipolysis. In pigs, PET-derived and corresponding measured FA fluxes (FA uptake, esterification, and triglyceride FA release) did not differ and were correlated with each other. In human beings, obese subjects had increased hepatic FA oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/- 0.01 vs 0.08 +/- 0.01 micromol/min/mL; P = .0007); FA uptake and esterification rates did not differ between obese subjects and controls. Liver FA oxidation correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r = 0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA esterification correlated with the systemic release of FA into plasma (r = 0.71, P = .003). PET imaging can be used to measure FA metabolism in the liver. By using this technology, we found that obese individuals have increased hepatic oxidation of FA, in the context of adipose tissue insulin resistance, and increased FA flux from visceral fat. FA flux from visceral fat is proportional with the mass of the corresponding depot. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Copy number variations of obesity relevant loci associated with body mass index in young Chinese.

PubMed

Sun, Chen; Cao, Min; Shi, Juan; Li, Lijuan; Miao, Lin; Hong, Jie; Cui, Bin; Ning, Guang

2013-03-10

Obesity is one of the most complex human diseases that are widely concerned and studied. More recently, copy number variations (CNVs) emerge as another important genetic marker to influence various human diseases. To elucidate the relationship between obesity and CNVs, this current study selected obesity-related candidate CNVs and analyzed their association with body mass index (BMI). Results showed that a CNV locus, 8q24.3, was significantly different (P=0.0070) in CNV frequency between the obese and healthy controls in a young eastern Chinese cohort, while no statistical significance was observed in other seven candidate loci including well reported 10q11.22 and 16p11.2 loci. The association of 8q24.3 CNVs with BMI of the subjects only showed marginal significance, while the copy number (CN) of 5p15.33 had a significant correlation with the BMI of the subject. These results suggested that 8q24.3 CN gains was associated with obesity, and 5p15.33 might also contribute to obesity pathogenesis, highlighting the importance of these CNVs for obesity risks, as well as providing new evidence for CNVs in the pathology of common diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes.

PubMed

Hodge, Rebecca J; Paulik, Mark A; Walker, Ann; Boucheron, Joyce A; McMullen, Susan L; Gillmor, Dawn S; Nunez, Derek J

2016-01-01

Nutritional agents have modest efficacy in reducing weight and blood glucose in animal models and humans, but combinations are less well characterized. GSK2890457 (GSK457) is a combination of 4 nutritional agents, discovered by the systematic assessment of 16 potential components using the diet-induced obese mouse model, which was subsequently evaluated in a human study. In the diet-induced obese mouse model, GSK457 (15% w/w in chow) given with a long-acting glucagon-like peptide -1 receptor agonist, exendin-4 AlbudAb, produced weight loss of 30.8% after 28 days of treatment. In db/db mice, a model of diabetes, GSK457 (10% w/w) combined with the exendin-4 AlbudAb reduced glucose by 217 mg/dL and HbA1c by 1.2% after 14 days. GSK457 was evaluated in a 6 week randomized, placebo-controlled study that enrolled healthy subjects and subjects with type 2 diabetes to investigate changes in weight and glucose. In healthy subjects, GSK457 well tolerated when titrated up to 40 g/day, and it reduced systemic exposure of metformin by ~ 30%. In subjects with diabetes taking liraglutide 1.8 mg/day, GSK457 did not reduce weight, but it slightly decreased mean glucose by 0.356 mmol/L (95% CI: -1.409, 0.698) and HbAlc by 0.065% (95% CI: -0.495, 0.365), compared to placebo. In subjects with diabetes taking metformin, weight increased in the GSK457-treated group [adjusted mean % increase from baseline: 1.26% (95% CI: -0.24, 2.75)], and mean glucose and HbA1c were decreased slightly compared to placebo [adjusted mean glucose change from baseline: -1.22 mmol/L (95% CI: -2.45, 0.01); adjusted mean HbA1c change from baseline: -0.219% (95% CI: -0.910, 0.472)]. Our data demonstrate remarkable effects of GSK457 in rodent models of obesity and diabetes, but a marked lack of translation to humans. Caution should be exercised with nutritional agents when predicting human efficacy from rodent models of obesity and diabetes. ClinicalTrials.gov NCT01725126.

HOMA-IR Values are Associated With Glycemic Control in Japanese Subjects Without Diabetes or Obesity: The KOBE Study.

PubMed

Hirata, Takumi; Higashiyama, Aya; Kubota, Yoshimi; Nishimura, Kunihiro; Sugiyama, Daisuke; Kadota, Aya; Nishida, Yoko; Imano, Hironori; Nishikawa, Tomofumi; Miyamatsu, Naomi; Miyamoto, Yoshihiro; Okamura, Tomonori

2015-01-01

Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men. HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals—Depot differences and dysmetabolism implications

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

Pestana, Diogo, E-mail: diogopestana@gmail.com; CINTESIS—Center for Research in Health Technologies and Information Systems, P-4200-450 Porto; Faria, Gil

Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) weremore » collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (R{sub S}=0.310, p<0.01) and duration of obesity (R{sub S}=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (R{sub S}=0.277, p<0.01), with relevance for vAT (R{sub S}=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to

Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects.

PubMed

Davison, K; Coates, A M; Buckley, J D; Howe, P R C

2008-08-01

Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2). A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05). Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.

A common core microbiota between obese individuals and their lean relatives? Evaluation of the predisposition to obesity on the basis of the fecal microflora profile.

PubMed

Elli, M; Colombo, O; Tagliabue, A

2010-10-01

Obesity represents a crucial social problem in developed countries as a cause of multiple metabolic abnormalities. The exact etiology of this multifactorial disease is still unknown. The impact of dietary habits and lifestyle is currently under investigation but the role of other predisposing factors, such as genetic determinants and familial history, needs still to be elucidated. Significant alterations in the composition of the intestinal microbiota have been recently identified in obese mice, suggesting an involvement of gut microbes in obesity. In humans, obese subjects are supposed to have a more efficient flora in energy extraction from food, due to the detection of quantitative differences in the major bacterial groups in obese subjects compared to lean ones. Despite these observations, the homologies in gut microbiota between obese adults and their lean relatives have never been investigated in details. Few reports about the detection of common microbial profiles between members of the same family have been published in the past but only one recent scientific article, investigating the presence of a common core microbiota between obese and lean twins, correlates genetic background and gut microflora as significant variables in obesity. The hypothesis suggested herein is that the identification of a familial-specific core microbiota could be precious in order to identify key-bacterial groups to be used as biomarkers for the evaluation of predisposition to obesity. Copyright 2010 Elsevier Ltd. All rights reserved.

Gender discrimination, gender disparities in obesity and human development.

PubMed

Ferretti, Fabrizio; Mariani, Michele

2017-03-01

Measuring gender inequality and women's empowerment is essential to understand the determinants of gender gaps, evaluate policies and monitor countries' progress. With this aim, over the past two decades, research has mainly been directed towards the development of composite indices. The purpose of this paper is to introduce a new and interdisciplinary perspective to the current debate on measuring gender inequality in human development. As a starting point, we develop a simple macroeconomic model of the interdependence between human development and gender inequality. We then introduce a biometric indicator, based on the ratio of female to male body mass index, to measure women's empowerment at the country level. Finally, by using the latest available data, we examine the ability of this biometric indicator to capture countries' performance in achieving gender equality. We obtain five main results: 1) we provide a theoretical framework to explain the joint determination of human development and gender inequality; 2) we show how to use this framework to simulate the impact of exogenous shocks or policy changes; 3) we demonstrate that exogenous changes have a direct and a multiplier effect on human development and gender inequality; 4) we find that the distribution of obesity between the female and male populations represents a useful proxy variable for measuring gender equality at the country level; 5) finally, we use these results to integrate and develop existing knowledge on the 'ecological' approach to the overweight and obesity pandemic.

Energy expenditure and physical activity in Prader-Willi syndrome: comparison with obese subjects.

PubMed

Butler, Merlin G; Theodoro, Mariana F; Bittel, Douglas C; Donnelly, Joseph E

2007-03-01

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder characterized by hypotonia, suck and feeding difficulties, hypogonadism, small hands and feet, developmental delay, hyperphagia and early childhood obesity and a particular facial appearance. The obesity associated with PWS is the result of a chronic imbalance between energy intake and energy expenditure (EE) due to hyperphagia, decreased physical activity, reduced metabolic rate and an inability to vomit. EE is affected by body composition as well as exercise. Individuals with PWS have a lower lean body mass (LBM) compared with controls which may contribute to reduced basal level EE. To determine the relationship among body composition, activity levels and metabolic rates, dual energy X-ray absorptiometry (DEXA) and a whole-room respiration chamber were used to measure body composition, total EE (TEE), resting EE (REE), physical activity, and mechanical work (MW) during an 8 hr monitoring period. The chamber consisted of a live-in whole-room indirect calorimeter equipped with a force platform floor to allow simultaneous measurement of EE, physical activity, and work efficiency during spontaneous activities and standardized exercise. Participants with PWS (27 with 15q11-q13 deletion and 21 with maternal disomy 15 with an average age of 23 years) had significantly decreased TEE by 20% and reduced LBM compared to 24 obese subjects. Similarly, REE was significantly reduced by 16% in the individuals with PWS relative to the comparison subjects. Total MW performed during the 8 hr monitoring period was significantly reduced by 35% in the PWS group. The energy cost of physical activity is related to the duration, intensity and type of activity and the metabolic efficiency of the individual. After adjusting group differences in LBM by analysis of variance, TEE and REE were no longer different between the two groups. Our data indicate that there is a significant reduction of EE in individuals with PWS

Accuracy of food intake reporting in obese subjects with metabolic risk factors.

PubMed

Svendsen, Mette; Tonstad, Serena

2006-03-01

The aim of the present study was to determine the accuracy of reported energy intake according to a food-frequency questionnaire (FFQ) and dietary records (DR) in obese subjects with metabolic syndrome risk factors. Subjects were twenty-three men and twenty-seven women with mean BMI of 35.7 (range 30.5-43.8) kg/m(2) who participated in a dietary interview based on a FFQ and completed weighed DR. Total energy expenditure was measured with the doubly labelled water method. Total energy expenditure, measured RMR and physical activity level did not differ between under-reporters (50 % of the sample) and non-under-reporters. Under-reporters had lower median intake of sweets, desserts and snacks than non-under-reporters (100 v. 161 g/d (P = 0.0008) and 61 v. 128 g/d (P = 0.0002) according to the FFQ and DR, respectively). The DR also showed lower energy density (6.7 (sd 1.3) v. 7.9 (SD 1.6) kJ/g; P = 0.0064), lower intake of sugary drinks (0 v. 167 g/d; P = 0.0063) and higher scores for dietary restraint (9.0 (sd 5.0) v. 6.1 (SD 3.5); P = 0.0285) in under-reporters. Energy density was associated with accuracy according to the FFQ (Spearman's rank correlation coefficient (RS) 0.406; P = 0.0034) and the DR (RS 0.537; P < 0.0001). In multivariate analysis, consumption of bread and sweets, desserts and snacks measured by the FFQ was positively associated with accuracy (R(2)adjusted 0.46 (95 % CI 0.32, 0.70)). According to the DR, consumption of sweets, desserts and snacks was also associated with accuracy, as was dietary restraint (inversely) (R(2)adjusted 0.67 (95 % CI 0.54, 0.83)). In obese subjects with metabolic risk factors, intake of sweets, desserts and snacks, bread and dietary restraint were determinants of reporting accuracy.

Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects.

PubMed

Stenlöf, Kaj; Wernstedt, Ingrid; Fjällman, Ted; Wallenius, Ville; Wallenius, Kristina; Jansson, John-Olov

2003-09-01

Recently, we demonstrated that intracerebroventricular injection of IL-6 increases energy expenditure and decreases body fat in rodents. Therefore, IL-6 may play a role in appetite and body weight control in the central nervous system. In the present study we evaluated cerebrospinal fluid (CSF) and serum IL-6 levels in humans in relation to body fat content and to CSF and serum levels of leptin. Thirty-two healthy overweight/obese male subjects with a body mass index range of 29.3-36.0 kg/m(2) were studied. Total and sc body fat were measured by dual energy x-ray absorptiometry and computed tomography, respectively. CSF IL-6 levels were in some individuals higher than serum IL-6 levels and correlated negatively with total body weight, sc and total body fat. In contrast, CSF leptin levels were 30-60 times lower than serum leptin levels and correlated positively with serum leptin, body weight, sc and total body fat. Furthermore, there was a negative correlation between CSF IL-6 and leptin. In conclusion, CSF IL-6 differs in many ways from CSF leptin. CSF IL-6 may be locally produced rather than serum derived, and body fat-regulating regions in the central nervous system may be exposed to insufficient IL-6 levels in more severe obesity.

48 CFR 352.270-4 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... regulatory requirements or ethical issues pertaining to research involving human subjects. (End of provision... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Protection of human subjects. 352.270-4 Section 352.270-4 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES...

48 CFR 352.270-4 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... regulatory requirements or ethical issues pertaining to research involving human subjects. (End of provision... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Protection of human subjects. 352.270-4 Section 352.270-4 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES...

48 CFR 352.270-4 - Protection of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... regulatory requirements or ethical issues pertaining to research involving human subjects. (End of provision... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Protection of human subjects. 352.270-4 Section 352.270-4 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES...

48 CFR 352.270-4 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... regulatory requirements or ethical issues pertaining to research involving human subjects. (End of provision... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Protection of human subjects. 352.270-4 Section 352.270-4 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES...

48 CFR 352.270-4 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... regulatory requirements or ethical issues pertaining to research involving human subjects. (End of provision... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Protection of human subjects. 352.270-4 Section 352.270-4 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES...

48 CFR 1523.303-70 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Protection of human... Hazardous Material and Material Safety Data 1523.303-70 Protection of human subjects. Contracting Officers shall insert the contract clause at 1552.223-70 when the contract involves human test subjects. ...

48 CFR 1523.303-70 - Protection of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Protection of human... Hazardous Material and Material Safety Data 1523.303-70 Protection of human subjects. Contracting Officers shall insert the contract clause at 1552.223-70 when the contract involves human test subjects. ...

48 CFR 1523.303-70 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Protection of human... Hazardous Material and Material Safety Data 1523.303-70 Protection of human subjects. Contracting Officers shall insert the contract clause at 1552.223-70 when the contract involves human test subjects. ...

48 CFR 1523.303-70 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Protection of human... Hazardous Material and Material Safety Data 1523.303-70 Protection of human subjects. Contracting Officers shall insert the contract clause at 1552.223-70 when the contract involves human test subjects. ...

48 CFR 1523.303-70 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Protection of human... Hazardous Material and Material Safety Data 1523.303-70 Protection of human subjects. Contracting Officers shall insert the contract clause at 1552.223-70 when the contract involves human test subjects. ...

Subjective Quantitative Studies of Human Agency

ERIC Educational Resources Information Center

Alkire, Sabina

2005-01-01

Amartya Sen's writings have articulated the importance of human agency, and identified the need for information on agency freedom to inform our evaluation of social arrangements. Many approaches to poverty reduction stress the need for empowerment. This paper reviews "subjective quantitative measures of human agency at the individual level." It…

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

Diurnal Variation of Sweet Taste Recognition Thresholds Is Absent in Overweight and Obese Humans

PubMed Central

Sanematsu, Keisuke; Nakamura, Yuki; Nomura, Masatoshi; Shigemura, Noriatsu; Ninomiya, Yuzo

2018-01-01

Sweet taste thresholds are positively related to plasma leptin levels in normal weight humans: both show parallel diurnal variations and associations with postprandial glucose and insulin rises. Here, we tested whether this relationship also exists in overweight and obese (OW/Ob) individuals with hyperleptinemia. We tested 36 Japanese OW/Ob subjects (body mass index (BMI) > 25 kg/m2) for recognition thresholds for various taste stimuli at seven different time points from 8:00 a.m. to 10:00 p.m. using the staircase methodology, and measured plasma leptin, insulin, and blood glucose levels before each taste threshold measurement. We also used the homeostatic model assessment of insulin resistance (HOMA-IR) to evaluate insulin resistance. The results demonstrated that, unlike normal weight subjects, OW/Ob subjects showed no significant diurnal variations in the recognition thresholds for sweet stimuli but exhibited negative associations between the diurnal variations of both leptin and sweet recognition thresholds and the HOMA-IR scores. These findings suggest that in OW/Ob subjects, the basal leptin levels (~20 ng/mL) may already exceed leptin’s effective concentration for the modulation of sweet sensitivity and that this leptin resistance-based attenuation of the diurnal variations of the sweet taste recognition thresholds may also be indirectly linked to insulin resistance in OW/Ob subjects. PMID:29498693

48 CFR 1252.223-72 - Protection of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Protection of human....223-72 Protection of human subjects. As prescribed in (TAR) 48 CFR 1223.7000(b), insert the following clause: Protection of Human Subjects (APR 2005) The Contractor shall comply with the National Highway...

48 CFR 1252.223-72 - Protection of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Protection of human....223-72 Protection of human subjects. As prescribed in (TAR) 48 CFR 1223.7000(b), insert the following clause: Protection of Human Subjects (APR 2005) The Contractor shall comply with the National Highway...

48 CFR 1252.223-72 - Protection of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Protection of human....223-72 Protection of human subjects. As prescribed in (TAR) 48 CFR 1223.7000(b), insert the following clause: Protection of Human Subjects (APR 2005) The Contractor shall comply with the National Highway...

48 CFR 1252.223-72 - Protection of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Protection of human....223-72 Protection of human subjects. As prescribed in (TAR) 48 CFR 1223.7000(b), insert the following clause: Protection of Human Subjects (APR 2005) The Contractor shall comply with the National Highway...

48 CFR 1252.223-72 - Protection of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Protection of human....223-72 Protection of human subjects. As prescribed in (TAR) 48 CFR 1223.7000(b), insert the following clause: Protection of Human Subjects (APR 2005) The Contractor shall comply with the National Highway...

Underestimation of urinary albumin to creatinine ratio in morbidly obese subjects due to high urinary creatinine excretion.

PubMed

Guidone, Caterina; Gniuli, Donatella; Castagneto-Gissey, Lidia; Leccesi, Laura; Arrighi, Eugenio; Iaconelli, Amerigo; Mingrone, Geltrude

2012-04-01

Albuminuria, a chronic kidney and/or cardiovascular disease biomarker, is currently measured as albumin-to-creatinine ratio (ACR). We hypothesize that in severely obese individuals ACR might be abnormally low in spite of relatively high levels of urinary albumin due to increased creatininuria. One-hundred-eighty-four subjects were divided into tertiles based on their BMI. Fat-free mass (FFM) and fat-mass were assessed by DEXA; 24-h creatinine and albumin excretion, ACR, lipid profile and blood pressure were measured. Twenty-four-hour creatinine highly correlated (R = 0.75) with FFM. Since both creatininuria and albuminuria increased with the BMI, being the increase in creatininuria preponderant in subjects with BMI>35, their ratio (AC-ratio) did not change significantly from that of subjects in the lower BMI tertile. ACR only correlated with the systolic blood pressure, while both albuminuria and cretininuria correlated (P = 0.01) with the absolute 10-year CHD risk. In subjects with BMI>35, 100 mg of albumin excreted with urine increased the CHD risk of 2%. Albumin-to-creatinine ratio is underestimated in severely obese individuals as a consequence of the large creatininuria, which is proportional to the increased FFM. Therefore, at least in this population 24-h albuminuria should be more reliable than ACR. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

What model organisms and interactomics can reveal about the genetics of human obesity.

PubMed

Williams, Michael J; Almén, Markus S; Fredriksson, Robert; Schiöth, Helgi B

2012-11-01

Genome-wide association studies have identified a number of genes associated with human body weight. While some of these genes are large fields within obesity research, such as MC4R, POMC, FTO and BDNF, the majority do not have a clearly defined functional role explaining why they may affect body weight. Here, we searched biological databases and discovered 33 additional genes associated with human obesity (CADM2, GIPR, GPCR5B, LRP1B, NEGR1, NRXN3, SH2B1, FANCL, GNPDA2, HMGCR, MAP2K5, NUDT3, PRKD1, QPCTL, TNNI3K, MTCH2, DNAJC27, SLC39A8, MTIF3, RPL27A, SEC16B, ETV5, HMGA1, TFAP2B, TUB, ZNF608, FAIM2, KCTD15, LINGO2, POC5, PTBP2, TMEM18, TMEM160). We find that the majority have orthologues in distant species, such as D. melanogaster and C. elegans, suggesting that they are important for the biology of most bilateral species. Intriguingly, signalling cascade genes and transcription factors are enriched among these obesity genes, and several of the genes show properties that could be useful for potential drug discovery. In this review, we demonstrate how information from several distant model species, interactomics and signalling pathway analysis represents an important way to better understand the functional diversity of the surprisingly high number of molecules that seem to be important for human obesity.

Animal models of exercise and obesity.

PubMed

Kasper, Christine E

2013-01-01

Animal models have been invaluable in the conduct of nursing research for the past 40 years. This review will focus on specific animal models that can be used in nursing research to study the physiologic phenomena of exercise and obesity when the use of human subjects is either scientifically premature or inappropriate because of the need for sampling tissue or the conduct of longitudinal studies of aging. There exists an extensive body of literature reporting the experimental use of various animal models, in both exercise science and the study of the mechanisms of obesity. Many of these studies are focused on the molecular and genetic mechanisms of organ system adaptation and plasticity in response to exercise, obesity, or both. However, this review will narrowly focus on the models useful to nursing research in the study of exercise in the clinical context of increasing performance and mobility, atrophy and bedrest, fatigue, and aging. Animal models of obesity focus on those that best approximate clinical pathology.

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

A one-way text messaging intervention for obesity.

PubMed

Ahn, Ahleum; Choi, Jaekyung

2016-04-01

Worldwide, there has been a startling increase in the number of people who are obese or overweight. Obesity increases the risk of cardiovascular disease and overall mortality. Mobile phone messaging is an important means of human communication globally. Because the mobile phone can be used anywhere at any time, mobile phone messaging has the potential to manage obesity. We investigated the effectiveness of a one-way text messaging intervention for obesity. Participants' body mass index and waist circumference were measured at the beginning of the programme and again after 12 weeks. The text message group received text messages about exercise, dietary intake, and general information about obesity three times a week, while the control group did not receive any text messages from the study. Of the 80 participants, 25 subjects in the text message group and 29 participants in the control group completed the study. After adjusting for baseline body mass index, the body mass index was significantly lower in the text message group than in the control group (27.9 vs. 28.3; p = 0.02). After adjusting for the baseline waist circumference, the difference of waist circumference between the text message group and control group was not significant (93.4 vs. 94.6; p = 0.13). The one-way text messaging intervention was a simple and effective way to manage obesity. The one-way text messaging intervention may be a useful method for lifestyle modification in obese subjects. © The Author(s) 2015.

Childhood Obesity, Obesity Treatment Outcome, and Achieved Education: A Prospective Cohort Study.

PubMed

Hagman, Emilia; Danielsson, Pernilla; Brandt, Lena; Svensson, Viktoria; Ekbom, Anders; Marcus, Claude

2017-10-01

Childhood obesity represents a social burden. This study aims to investigate whether achieved educational level differs in young adults who have suffered obesity in childhood compared with the general population and to determine how obesity treatment influences achieved educational level. This prospective cohort study includes subjects from the Swedish Childhood Obesity Treatment Registry (BORIS, n = 1,465) who were followed up after 20 years of age. They were compared with a randomly selected matched population-based group (n = 6,979). Achieved educational level was defined as ≥12 years in school (completers). Covariates include sex, migration background, and attention deficit disorders for both groups. Furthermore, age and degree of obesity at start of obesity treatment, treatment duration, and efficacy were analyzed in the obese cohort. In the obese cohort, 55.4% were school completers, compared with 76.2% in the comparison group (adjusted odds ratio [OR] = .42, p < .0001). Subjects with moderate obesity had a completion rate of 64.4%, compared with 50.9% among subjects with morbid obesity (adjusted OR = .57, p < .0001). Successful obesity treatment was associated with increased future educational level, compared with those experiencing no treatment effect (61.9% vs. 51.3% completers; adjusted OR = 1.4, p < .05). In children with attention deficit disorder, obesity was not an extra risk for not completing 12 or more years of schooling, p = .11. Obesity in childhood was associated with low educational level in early adulthood. Children and adolescents with obesity may require special support at school in addition to health care treatment to lose weight. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Differential Scavenging Among Pig, Rabbit, and Human Subjects.

PubMed

Steadman, Dawnie Wolfe; Dautartas, Angela; Kenyhercz, Michael W; Jantz, Lee M; Mundorff, Amy; Vidoli, Giovanna M

2018-04-12

Different animal species have been used as proxies for human remains in decomposition studies for decades, although few studies have sought to validate their use in research aimed at estimating the postmortem interval. This study examines 45 pig, rabbit, and human subjects placed in three seasonal trials at the Anthropology Research Facility. In an earlier paper, we found that overall decomposition trends did vary between species that could be due to differential insect and scavenger behavior. This study specifically examines if scavenger behavior differs by carrion species. Daily photographs, game camera photographs, written observations, and Total Body Score (TBS) documented scavenging and decomposition changes. Results show that raccoons were the most commonly observed vertebrate scavenger, that scavenging was most extensive in winter, and that certain human subjects were preferred over other humans and all non-human subjects. Finally, scavenging activity greatly reduces the accuracy of postmortem interval estimates based on TBS. © 2018 American Academy of Forensic Sciences.

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

PubMed

Belhocine, Kafia; Vavasseur, Fabienne; Volteau, Christelle; Flet, Laurent; Touchefeu, Yann; Bruley des Varannes, Stanislas

2014-07-15

Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37-55] vs. 30 [15-55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14-53] vs. 54 [19-130] and 95 [73-170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. ClinicalTrial.gov: NCT01136317.

Changes seen in gut bacteria content and distribution with obesity: causation or association?

PubMed

Bell, David S H

2015-01-01

In the microbiota of both obese animals and humans there is an increased ratio of the gram positive Firmicutes to the gram negative Bacteroidetes (the obesity pattern). To assess if altering this ratio in animals and humans would prevent obesity or reduce body weight in the obese subject this review was preformed. A survey of all the available English language literature utilizing Medline on this topic was obtained and critically reviewed. The key words that were utilized were gut microbiota, diet and obesity. In both humans and animals changes in diet, particularly the utilization of the high fat, high calorie Western diet, utilization of artificial sweeteners and disruption of the diurnal rhythm will quickly change the microbiota from a thin to an obese pattern. In animals, the transfer of an obese microbiota to germ free animals and thin animals results in obesity and the introduction of a lean microbiota will result in weight loss in obese animals. However, in humans similar changes in the gut microbiota induced with probiotics and prebiotics have not been shown to result in weight loss. In both animals and humans the most dramatic changes in the gut microbiota occur following weight loss resulting from a gastric bypass where there is a restoration to a normal Firmicutes to Bacteroidetes ratio. These changes could either be due to the dramatic change in the composition of the diet which occurs following this surgery or due to down-regulation of the Farnesoid X Receptor which causes a decrease in bile acid production and an elevation of the gut pH which in turn allows the regrowth of bacteria associated with weight loss which were previously unable to grow in the acidic intestinal environment caused by excess production of bile acids. In both humans and animals there are characteristic changes in the gut microbiota associated with obesity. In animals but not in humans altering the microbiota can result in weight loss and weight gain which does not occur in

The Gut Microbiota from Lean and Obese Subjects Contribute Differently to the Fermentation of Arabinogalactan and Inulin

PubMed Central

Aguirre, Marisol; Bussolo de Souza, Carlota; Venema, Koen

2016-01-01

Background An aberrant metabolic activity or a compositional alteration of the gut microbiota has been proposed as a factor that makes us more prone to disease. Therefore, we explored the effect of two dietary fibers (arabinogalactan and inulin) on the microbiota from lean and obese subjects during 72 h in vitro fermentation experiments using the validated TNO dynamic in vitro model of the proximal colon: TIM-2. Metabolically, arabinogalactan fermentation showed a higher production of propionate when compared to n-butyrate in the obese microbiota fermentations. In general, lean microbiota produced more n-butyrate from the fermentation of both substrates when compared to the obese microbiota. Furthermore, the obese microbiota extracted more energy from the fermentation of both fibers. Results Compositionally, bacteria belonging to Gemmiger, Dorea, Roseburia, Alistipes, Lactobacillus and Bifidobacterium genera were found to be highly abundant or stimulated by the prebiotics in the lean microbiota suggesting a potential role in leanness. Furthermore, a significant correlation between known butyrogenic strains including B. adolescentis, an unclassified Bifidobacterium and F. prausnitzii with this metabolite in the fermentation of inulin in both microbiotas was found. Conclusions Although supplementary in vivo studies are needed, the current study provides more evidence for the consumption of specific ingredients with the aim of modulating the gut microbiota in the context of obesity. PMID:27410967

HOMA-IR Values are Associated With Glycemic Control in Japanese Subjects Without Diabetes or Obesity: The KOBE Study

PubMed Central

Hirata, Takumi; Higashiyama, Aya; Kubota, Yoshimi; Nishimura, Kunihiro; Sugiyama, Daisuke; Kadota, Aya; Nishida, Yoko; Imano, Hironori; Nishikawa, Tomofumi; Miyamatsu, Naomi; Miyamoto, Yoshihiro; Okamura, Tomonori

2015-01-01

Background Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. Methods We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Results Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = −18.42, P = 0.009) only in men. Conclusions HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population. PMID:26005064

Human Protein Kinases and Obesity.

PubMed

Engin, Atilla

2017-01-01

The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases. These phosphatases remove phosphate groups from tyrosine and serine/threonine residues on their substrate. Dual-specificity phosphatases are important signal transduction enzymes that regulate various cellular processes in coordination with protein kinases. The protein kinase-phosphoproteins interactions play an important role in obesity . In obesity, the pro- and anti-inflammatory effects of adipokines and cytokines through intracellular signaling pathways mainly involve the nuclear factor kappa B (NF-kappaB) and the c-Jun N-terminal kinase (JNK) systems as well as the inhibitor of kappaB-kinase beta (IKK beta). Impairment of insulin signaling in obesity is largely mediated by the activation of the IKKbeta and the JNK. Furthermore, oxidative stress and endoplasmic reticulum (ER) stress activate the JNK pathway which suppresses insulin biosynthesis. Additionally, obesity-activated calcium/calmodulin dependent-protein kinase II/p38 suppresses insulin-induced protein kinase B phosphorylation by activating the ER stress effector, activating transcription factor-4. Obese adults with vascular endothelial dysfunction have greater endothelial cells activation of unfolded protein response stress sensors, RNA-dependent protein kinase-like ER eukaryotic initiation factor-2alpha kinase (PERK) and activating transcription factor-6. The transcriptional regulation of

Sociodemographic variations in obesity among Ghanaian adults.

PubMed

Amoah, Albert G B

2003-12-01

To determine the sociodemographic associations of obesity in Ghana. A cross-sectional descriptive study was conducted on a sample of 6300 adults aged 25 years and over who were selected by random cluster sampling. Two urban (high-class and low-class suburbs) and a rural community in Accra, Ghana. In total, 4731 (1857 males, 2874 females) subjects participated. Demographic data were obtained by a questionnaire and height and weight were determined with subjects in light clothing and without shoes. The overall crude prevalence of overweight and obesity was 23.4 and 14.1%, respectively. The rates of overweight (27.1 vs. 17.5%) and obesity (20.2 vs. 4.6%) were higher in females than males. Obesity increased with age up to 64 years. There were more overweight and obesity in the urban high-class residents compared with the low-class residents and in urban than rural subjects. Overweight and obesity were highest among the Akan and Ga tribes and relatively low among Ewes. Subjects with tertiary education had the highest prevalence of obesity (18.8%) compared with less literate and illiterate subjects (12.5-13.8%). Subjects whose jobs were of a sedentary nature had higher levels of obesity (15%) than subjects whose jobs involved heavy physical activity (10%). Subjects who did not engage in leisure-time physical activity were more obese than those who had three or more sessions of leisure-time physical activity per week (15.3 vs. 13.5%). Overweight and obesity are common among residents in the Accra area. Older age, female gender, urban, high-class residence, sedentary occupation and tertiary education were associated with higher levels of obesity. Policies and programmes that promote healthy lifestyles may prove beneficial.

Treatment of body composition changes in obese and overweight older adults: insight into the phenotype of sarcopenic obesity.

PubMed

Poggiogalle, Eleonora; Migliaccio, Silvia; Lenzi, Andrea; Donini, Lorenzo Maria

2014-12-01

In recent years, mounting interest has been directed to sarcopenic obesity (SO), given the parallel increase of life expectancy and prevalence of obesity in Western countries. The phenotype of SO is characterized by the coexistence of excess fat mass and decreased muscle mass, leading to the impairment of physical performance. The aim of the present review was to summarize the impact of different treatment strategies contrasting body composition changes in older obese and overweight subjects, providing insight into the SO phenotype. Revision questions were formulated; relevant articles were identified from Pubmed through a systematic search strategy: definition of the search terms (sarcopenic obesity, diet, nutritional supplements, physical activity, exercise, pharmacological treatment); limits: papers published in the last 10 years; humans; age ≥ 60 years old; body mass index >25 kg/m(2); language: English. Studies dealing with sarcopenia associated to cancer cachexia or neurological diseases, any malignant disease, inflammatory or autoimmune diseases, corticosteroids for systemic use, bedridden subjects, and syndromic obesity were excluded. 14 articles were identified for inclusion in the present systematic review, and were grouped basing on the type of the main intervention: data assessing body composition changes after combined lifestyle interventions, exercise/physical activity, dietary interventions, and pharmacological treatment. Most of the studies were randomized, controlled. Sample size ranged from 12 to 439 subjects, and study duration varied from 6 weeks to 12 months. Weight loss based on diet combined with exercise seems to be the best strategy to adopt for treatment of phenotypic aspects of SO, improving metabolic consequences related to excess fat, preserving lean mass, and allowing functional recovery.

The effect of moderate weight loss, with or without (1, 3)(1, 6)-β-glucan addition, on subcutaneous adipose tissue inflammatory gene expression in young subjects with uncomplicated obesity.

PubMed

Strączkowski, Marek; Nikołajuk, Agnieszka; Majewski, Radosław; Filarski, Remigiusz; Stefanowicz, Magdalena; Matulewicz, Natalia; Karczewska-Kupczewska, Monika

2018-05-08

Obesity is characterized by insulin resistance and low-grade systemic and adipose tissue (AT) inflammation. It remains unclear whether beneficial effects of weight loss are related to AT inflammation. We aimed to assess the effect of weight loss during low-calorie diet on insulin sensitivity, AT expression of genes associated with inflammation in young subjects with obesity. Furthermore, we estimated the effects of immunomodulatory (1, 3)(1, 6)-β-glucan (BG) on the above parameters. The study group comprised 52 subjects with obesity. Twelve-week dietary intervention was applied, with randomization to receive or not 500 mg BG daily. Euglycemic hyperinsulinemic clamp, subcutaneous AT biopsy were performed before and after the program. Twenty normal-weight subjects, examined at baseline, served as a control group. At baseline, obese subjects had lower insulin sensitivity, lower AT ADIPOQ, JAK1, and JAK2 expression and higher AT expression of LEP, IL6ST, STAT3, MIF, CCL2, MMP9, and IL18. Forty obese subjects completed dietary intervention program, which resulted in 11.3% weight loss and 27% increase in insulin sensitivity (both p < 0.0001). AT IL6R, IL6ST, JAK1, and JAK2 expression increased, whereas MIF, CCL2, MMP9, and IL18 gene expression did not change in response to weight loss. BG addition had no effect on any of the parameters studied. Our data indicate that reduction in AT inflammation is not required for an improvement in insulin action during weight loss in subjects with uncomplicated obesity. BG does not have effects during dietary intervention.

The genetics of human obesity.

PubMed

Xia, Qianghua; Grant, Struan F A

2013-04-01

It has long been known that there is a genetic component to obesity, and that characterizing this underlying factor would likely offer the possibility of better intervention in the future. Monogenic obesity has proved to be relatively straightforward, with a combination of linkage analysis and mouse models facilitating the identification of multiple genes. In contrast, genome-wide association studies have successfully revealed a variety of genetic loci associated with the more common form of obesity, allowing for very strong consensus on the underlying genetic architecture of the phenotype for the first time. Although a number of significant findings have been made, it appears that very little of the apparent heritability of body mass index has actually been explained to date. New approaches for data analyses and advances in technology will be required to uncover the elusive missing heritability, and to aid in the identification of the key causative genetic underpinnings of obesity. © 2013 New York Academy of Sciences.

Committees for Ethics in Research involving human subjects.

PubMed

Hossne, William Saad; Vieira, Sonia; De Freitas, Corina Bontempo Duca

2008-01-01

In Brazil since October 1996 there have been guidelines for research involving human subjects. Now human subjects know when their treatment is part of research. Deceit is no longer tolerated. But is not enough to say we offer an explanation to the potential subject and we offer a choice before he or she is confronted with an informed consent form. As in all professional activity, scientific investigation needs social controls. In Brazil, the ultimate responsibility of an investigation lies on the investigator, but in every institution where research is carried out there is a Committee for Ethics in Research. All Committees are subordinated to the National Commission of Ethics in Research, which is submitted to the Brazilian Institute of Health. During 2005 around 17,000 protocols involving 700,000 human subjects were revised by 475 Committees distributed all over the country. Approximately 7,000 people are now working in these Committees.

Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity

PubMed Central

2012-01-01

Background The use of chromium supplements is widespread for the prevention and treatment of diabetes mellitus but there are conflicting reports on efficacy, possibly reflecting discrepant effects across different populations. In the present studies, we test the hypothesis that chromium supplementation raises serum chromium levels and correspondingly improves insulin sensitivity. Methods A double blind placebo-controlled randomized trial was conducted on 31 non-obese, normoglycemic subjects. After baseline studies, the subjects were randomized to placebo or chromium picolinate 500 μg twice a day. The primary endpoint was change in insulin sensitivity as measured by euglycemic hyperinsulinemic clamp. Pre-specified secondary endpoints included fasting lipids, blood pressure, weight, body composition measured by DXA scan. Results After 16 weeks of chromium picolinate therapy there was no significant change in insulin sensitivity between groups (p=0.83). There was, however, a strong association between serum chromium and change in insulin resistance (β = -0.83, p=0.01), where subjects with the highest serum chromium had a worsening of insulin sensitivity. This effect could not be explained by changes in physiological parameters such as body weight, truncal fat and serum lipids with chromium therapy. Conclusions Chromium therapy did not improve insulin sensitivity in non-obese normoglycemic individuals. Further, subjects who have high serum chromium levels paradoxically had a decline in insulin sensitivity. Caution therefore should be exercised in recommending the use of this supplement. Trial registration The study was registered on the NIH registry (clinicaltrials.gov) and the identifier is NCT00846248 PMID:23194380

Obesity, expression of adipocytokines, and macrophage infiltration in canine mammary tumors.

PubMed

Lim, H Y; Im, K S; Kim, N H; Kim, H W; Shin, J I; Sur, J H

2015-03-01

Obesity influences the development, progression and prognosis of human breast cancer and canine mammary cancer (MC) but the precise underlying mechanism is not well-documented in the fields of either human or veterinary oncology. In the present study, the expression of major adipocytokines, including leptin, adiponectin, and leptin receptor (ObR) in benign (n = 28) and malignant (n = 70) canine mammary tumors was investigated by immunohistochemistry and on the basis of the subject's body condition score (BCS). To evaluate the relationship between obesity and chronic inflammation of the mammary gland, macrophages infiltrating within and around tumoral areas were counted. The mean age of MC development was lower in overweight or obese dogs (9.0 ± 1.8 years) than in lean dogs or optimal bodyweight (10.2 ± 2.9 years), and the evidence of lymphatic invasion of carcinoma cells was found more frequently in overweight or obese group than in lean or optimal groups. Decreased adiponectin expression and increased macrophage numbers in overweight or obese subjects were significantly correlated with factors related to a poor prognosis, such as high histological grade and lymphatic invasion. Leptin expression was correlated with progesterone receptor status, and ObR expression was correlated with estrogen receptor status of MCs, regardless of BCS. Macrophage infiltration within and around the tumor may play an important role in tumor progression and metastasis in obese female dogs and may represent a prognostic factor for canine MCs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Central obesity and the Mediterranean diet: A systematic review of intervention trials.

PubMed

Bendall, C L; Mayr, H L; Opie, R S; Bes-Rastrollo, M; Itsiopoulos, C; Thomas, C J

2017-10-17

Central obesity is associated with chronic low-grade inflammation, and is a risk factor for cardiometabolic syndrome. The Mediterranean diet pattern has a convincing evidence-base for improving cardiometabolic health. This review investigated the impact of Mediterranean diet interventions on central obesity, specifically. A systematic literature search was conducted in the MEDLINE, CINAHL, EMBASE and Cochrane library databases. Search terms included: 'Mediterranean Diet', 'Mediterranean dietary pattern', 'central obesity' and 'visceral fat'. The search was limited to English language and humans ≥18 years. Eighteen articles met the eligibility criteria and reported at least one outcome measure of central obesity with Mediterranean diet intervention. Central obesity measures included waist circumference (16 studies), waist-hip ratio (5 studies) and visceral fat (2 studies). Thirteen (72%) of the studies, totaling 7186 subjects (5168 subjects assigned to a Mediterranean Diet), reported a significant reduction in central obesity with a Mediterranean-type diet. However, seven out of these 13 interventions employed energy restriction, and only three showed a statistically significant favorable effect of the Mediterranean diet relative to a control group. This systematic review highlights the potential for a Mediterranean diet intervention to reduce central obesity and in turn reduce obesity-related chronic disease risk and associated public health burden.

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...