Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism.

BACKGROUND/OBJECTIVES: Inter-individual variability in weight loss during obesity treatment is complex and poorly understood. Here we use whole body and tissue approaches to investigate fuel oxidation characteristics in skeletal muscle fibers, cells and distinct circulating protein biomarkers before and after a high fat meal (HFM) challenge in those who lost the most (obese diet-sensitive; ODS) vs the least (obese diet-resistant; ODR) amount of weight in a highly controlled weight management program. SUBJECTS/METHODS: In 20 weight stable-matched ODS and ODR women who previously completed a standardized clinical weight loss program, we analyzed whole-body energetics and metabolic parameters in vastus lateralis biopsies and plasma samples that were obtained in the fasting state and 6 h after a defined HFM, equivalent to 35% of total daily energy requirements. RESULTS: At baseline (fasting) and post-HFM, muscle fatty acid oxidation and maximal oxidative phosphorylation were significantly greater in ODS vs ODR, as was reactive oxygen species emission. Plasma proteomics of 1130 proteins pre and 1, 2, 5 and 6 h after the HFM demonstrated distinct group and interaction differences. Group differences identified S-formyl glutathione hydratase, heat shock 70 kDA protein 1A/B (HSP72), and eukaryotic translation initiation factor 5 (eIF5) to be higher in ODS vs ODR. Group-time differences included aryl hydrocarbon interacting protein (AIP), peptidylpropyl isomerase D (PPID) and tyrosine protein-kinase Fgr, which increased in ODR vs ODS over time. HSP72 levels correlated with muscle oxidation and citrate synthase activity. These proteins circulate in exosomes; exosomes isolated from ODS plasma increased resting, leak and maximal respiration rates in C2C12 myotubes by 58%, 21% and 51%, respectively, vs those isolated from ODR plasma. CONCLUSIONS: Findings demonstrate distinct muscle metabolism and plasma proteomics in fasting and post-HFM states corresponding in diet-sensitive vs diet-resistant obese women.

Obesity and type 2 diabetes in Northern Canada's remote First Nations communities: the dietary dilemma.

First Nations populations in Northwestern Ontario have undergone profound dietary and lifestyle transformations in less than 50 years, which have contributed to the alarming rise in obesity and obesity-related diseases, in particular type 2 diabetes mellitus. Even though the genetic background of First Nations peoples differs from that of the Caucasians, genetics alone cannot explain such a high prevalence in obesity and type 2 diabetes. Modifications in lifestyle and diet are major contributors for the high prevalence of chronic diseases. What remains constant in the literature is the persistent view that locally harvested and prepared foods are of tremendous value to First Nations peoples providing important health and cultural benefits that are increasingly being undermined by western-based food habits. However, the complexities of maintaining a traditional diet require a multifaceted approach, which acknowledges the relationship between benefits, risks and viability that cannot be achieved using purely conventional medical and biological approaches. This brief review explores the biological predispositions and potential environmental factors that contribute to the development of the high incidence of obesity and obesity-related diseases in First Nations communities in Northern Canada. It also highlights some of the complexities of establishing exact physiological causes and providing effective solutions.

Similar associations of total adiponectin and high molecular weight adiponectin with cardio-metabolic risk factors in a population of overweight and obese postmenopausal women: a MONET study.

The aim of the study was to examine the association between total adiponectin and high molecular weight (HMW) adiponectin levels with cardio-metabolic risk factors in a population of sedentary, overweight, and obese postmenopausal women. Cross-sectional study was carried out on 55 nondiabetic sedentary overweight and obese postmenopausal women aged between 50 and 70 years. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp technique. Body composition and visceral fat were measured using dual X-ray absorptiometry and computed tomography, respectively. Other cardio-metabolic risk factors included: plasma lipids, hsC-reactive protein, energy expenditure (doubly labeled water), peak oxygen consumption, muscle strength (using weight training equipment) as well as total and HMW adiponectin. Correlations of total and HMW adiponectin with various cardio-metabolic risk factors were comparable. In addition, regression analysis results showed similar independent predictors of total and HMW adiponectin. Finally, the receiver operator characteristic (ROC) curves for total and HMW adiponectin to predict insulin sensitivity showed no difference between the areas under curve (AUC) (AUC total adiponectin=0.80 [95% CI: 0.66-0.95] versus AUC HMW adiponectin=0.76 [95% CI: 0.60-0.91], p=0.36). The present study indicates that HMW adiponectin does not seem to provide additional information than total adiponectin in relation to cardio-metabolic risk factors in overweight/obese postmenopausal women.

Variation in C-reactive protein following weight loss in obese insulin resistant postmenopausal women: is there an independent contribution of lean body mass?

BACKGROUND: We showed that obese insulin resistant postmenopausal women are characterized by higher lean body mass and elevated C-reactive protein. Although counterintuitive, we hypothesized that losses in muscle mass following caloric restriction and increase in muscle quality will be associated with improvements in glucose homeostasis through decreases in C-reactive protein. OBJECTIVES: To determine 1) if improvements in C-reactive protein concentrations occurs through losses in lean body mass; and 2) if decreases in C-reactive protein levels contribute to improvements in insulin sensitivity. METHODS: 50 postmenopausal women (body mass index>26 kg/m(²)) with impaired glucose disposal (<7.5 mg/kg/min) completed a 6-month caloric restriction program. Outcome measures were: Glucose disposal rate: M value (by hyperinsulinemic-euglycemic clamp), body composition (total, trunk, and appendicluar). LBM and FM by DXA), LBM index (LBM (kg)/height (m(2)), body fat distribution (VAT and SAT by CT scan) and plasma high-sensitive C-reactive protein (hsCRP) and interleukin-6 (Il-6). RESULTS: Significant correlations were observed between Δ hsCRP levels with Δ Il-6 (r=0.33, p≤0.05), Δ total LBM index (r=0.44, p≤0.01), Δ trunk LBM (r=0.38, p≤0.01) Δ SAT (r=0.35, p≤0.05) and ∆ glucose disposal rate (r=- 0.44, p≤0.01). After including all the correlated variables in Stepwise linear regression model, Δ LBM index was the only independent predictor of the reduction in hsCRP levels (R(2)=0.20, p≤0.01). CONCLUSION: Losses in total lean body mass are independently associated with improvements in inflammatory state (CRP levels) in obese postmenopausal women with impaired glucose disposal.

Age-related differences in messenger ribonucleic acid expression of key proteins involved in adipose cell differentiation and metabolism.

This study was performed to compare the expression of key proteins [lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), complement 3 (C3), and peroxisome proliferator-stimulated receptor-gamma (PPAR gamma)] involved in sc abdominal adipose tissue (AT) metabolism of young (n = 13) vs. middle-aged (n = 16) men. The sc abdominal AT-LPL activity as well as fat cell lipolysis were also measured in both groups of men. Young and middle-aged men displayed similar body weight and sc abdominal fat accumulation, measured by computed tomography. However, middle-aged men were characterized by a higher percent body fat (28 +/- 5% vs. 22 +/- 7%; P < 0.05) than young subjects. No difference between groups was observed in sc abdominal adipose tissue LPL activity. On the other hand, maximal lipolytic responses of sc abdominal adipocytes to isoproterenol (beta-adrenergic agonist) or to postadrenoceptor agents such as dibutyryl cAMP, forskolin, and theophylline were lower in middle-aged than in young men (P < 0.05). AT-LPL messenger ribonucleic acid (mRNA) levels were similar regardless of the subject's age. However, HSL, C3, and PPAR gamma mRNA levels were higher in middle-aged than in young individuals (P < 0.01-0.05). After correction for percent body fat, only HSL and C3 mRNA levels remained significantly different between groups (P < 0.05). Taken together, these results suggest that aging has an effect on the up-regulation of HSL and C3 mRNA levels, whereas PPAR gamma expression seems to be related mainly to increased adiposity.

Subcutaneous adipose tissue metabolism at menopause: importance of body fatness and regional fat distribution.

The aim of this study was to examine the contribution of menopause per se on sc adipose tissue (AT) metabolism in 16 women classified on the basis of their menopausal status: 8 postmenopausal (mean +/- SD age, 57 +/- 6 yr) vs. 8 premenopausal individuals (37 +/- 5 yr). These 2 groups were matched for sc abdominal adipose cell size (within 0.02 microg lipid/cell) and visceral AT accumulation (within 15 cm2), measured by computed tomography. Fasting plasma glucose and insulin levels as well as their responses to an oral glucose load were similar regardless of the women's hormonal status. Subcutaneous abdominal and femoral AT lipoprotein lipase activities as well as fat cell lipolysis were determined in both groups. Epinephrine induced antilipolysis at low concentrations and lipolysis at higher doses in both adipose sites and groups. The maximal lipolytic response to epinephrine or to isoproterenol (beta-adrenergic agonist) as well as the maximal antilipolytic effect of either the catecholamine or UK-14304 (alpha2-adrenergic agonist) assessed in sc adipocytes were similar in pre- and postmenopausal women. In addition, neither the beta- nor the alpha2-adrenoceptor sensitivity of sc adipose cells differed according to subjects' age. Finally, maximal lipolysis promoted by postadrenoceptor agents and AT-lipoprotein lipase activity did not vary among adipose regions or between groups. Taken together, these results suggest that menopause per se does not influence sc AT metabolism once the variation related to adipose cell size and total body fatness is taken into account.

Adipose tissue metabolism in young and middle-aged men after control for total body fatness.

The aim of this study was to compare the sc adipose tissue metabolism of young (29 +/- 4 yr) vs. middle-aged men (57 +/- 5 yr), once the concomitant variation in total adiposity was taken into account. For this purpose, sc abdominal and femoral adipose tissue lipoprotein lipase activities, as well as fat cell lipolytic responses, were investigated in 2 groups of 16 men, differing in age but displaying similar adipose tissue mass (within 2 kg) and sc abdominal adipose tissue area, measured by computed tomography (within 15 cm2). No difference was observed in adipose tissue lipoprotein lipase activity of young vs. middle-aged subjects, regardless of the adipose region considered. Epinephrine induced antilipolysis at low concentrations (10(-9) to 10(-7) mol/L) and a net lipolytic response at higher doses (10(-6) to 10(-5) mol/L), regardless of the subjects' age and the anatomic location of fat. In addition, the selective alpha2-adrenergic agonist, UK-14304, promoted a similar antilipolytic response in sc abdominal and femoral adipose cells from both groups. However, maximal lipolysis induced by isoproterenol (beta-adrenergic agonist) or by postadrenoceptor agents such as dibutyryl-cAMP, forskolin, and theophylline were lower in both adipose regions of middle-aged (as compared with young) men. No difference in the beta- or the alpha2-adrenoceptor sensitivity of sc adipose cells was observed between groups. These results indicate that there is, with age, a selective decrease in the lipolytic capacity to beta-adrenergic agonist, which seems to be caused by postadrenoceptor impairments. Because subjects in the 2 age-groups displayed similar body fatness, these alterations are independent from the age-expected increase in total adiposity.

Energy balance and pollution by organochlorines and polychlorinated biphenyls.

Organochlorines are fat-soluble chemical compounds resistant to degradation, so they are stored in the adipose tissue of practically every organism on the planet, including humans. Accumulation of these compounds in the body seems to be related to fat mass, obese individuals having a higher plasma organochlorine concentration than lean subjects. During body weight loss, lipid mobilization and a decrease in fat mass result in increased concentrations of organochlorines in plasma and adipose tissue. Organochlorines may have adverse health effects. For example, they have been associated with altered immune and thyroid functions and with some types of cancer. As these compounds may reach their target organs whilst in the circulation, their increase in plasma during weight loss might be associated with some physiological changes occurring during weight loss. Relationships have indeed been reported among weight loss-induced increase in plasma organochlorine concentration and decreased triiodothyronine (T3) concentration, resting metabolic rate, and skeletal muscle markers for fat oxidation. Although further studies are needed to assess the causality of these relationships, they raise concern about some potential undesirable effects of weight loss. Indeed, the effects of organochlorines on energy balance could complicate body weight loss and even favour weight regain. These notions lend support for weight-loss strategies favouring a moderate weight loss, which would reduce risks for cardiovascular diseases, diabetes and hypertension, without resulting in a substantial release of organochlorines.

Increase in plasma pollutant levels in response to weight loss is associated with the reduction of fasting insulin levels in men but not in women.

Environmental pollutants can act as endocrine modulators. In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated with those in plasma insulin levels. Fasting insulin and the area under the curve (AUC) of insulin after a 75-g oral glucose load, plasma levels of 1 commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB)) were measured before and after a 15-week weight loss program induced by a caloric restriction in a sample of obese men and women. Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean +/- SD 9.4 +/- 4.1 v 5.9 +/- 5 kg, respectively, P <.05). Fasting insulin and AUC of insulin significantly decreased in men and women after the treatment. In response to weight loss, a significant increase in OC was observed in both genders, and this effect was more pronounced in men. The greater the increase in plasma OC levels, the greater the reduction in fasting insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in women (-.22 < r <.01, not significant [NS]). In both genders, no relationship was observed between changes in plasma OC levels and changes in AUC of insulin (-.41 < r < -.08, NS). In men, relationships between changes in plasma HCB, Aroclor 1260, and PCB-153 concentrations and those in fasting insulin levels in response to weight loss remained significantly correlated after correction for fat mass loss (-.46 < partial r < -.51, P values ranging from.05 to.07). These results suggest that weight loss-induced increase in plasma pollutant levels tends to be independently associated with the reduction of fasting insulin levels in men, but not in women. Further studies are needed to verify whether these findings are causally related.

Relationship of visceral adipose tissue to metabolic risk factors for coronary heart disease: is there a contribution of subcutaneous fat cell hypertrophy?

Visceral adipose tissue (VAT) accumulation is an important correlate of the metabolic complications found in obese patients. The aim of this study was to evaluate the respective contribution of VAT deposition versus subcutaneous abdominal or femoral fat cell hypertrophy as correlates of the metabolic risk profile in 69 men and 65 premenopausal women (aged 35+/-5 years) with a wide range of fatness (body mass index, 18 to 57 kg/m2). In both genders, VAT accumulation was positively correlated with fasting plasma insulin, triglyceride (TG), and low-density lipoprotein (LDL)-apolipoprotein B (apo B) levels and the cholesterol (CHOL)/high-density lipoprotein (HDL)-CHOL ratio (.24 < or = r < or = .71, P < .05). A similar pattern of positive relationships was found between subcutaneous abdominal fat cell weight and metabolic risk variables in men and women (.33 < or = r < or = .60, P < .01). Positive associations were also observed in women between femoral fat cell weight and fasting plasma insulin, TG, and CHOL levels and the CHOL/HDL-CHOL ratio (.29 < or = r < or = .42, P < .05). However, only plasma TG concentrations and the CHOL/HDL-CHOL ratio were positively correlated with femoral fat cell weight in men (r = .30, P < .05). To better investigate the relationships between the metabolic risk profile and hypertrophic subcutaneous obesity, individuals with small versus large subcutaneous abdominal adipocytes were matched according to VAT accumulation. Men with large abdominal fat cells displayed higher plasma TG and LDL-apo B levels compared with men characterized by small abdominal adipocytes (P < .05). Stepwise multiple regression analyses showed that subcutaneous abdominal fat cell weight was the best independent variable predicting plasma TG and LDL-apo B levels in men. No significant difference was found in the metabolic profile of subjects displaying small versus large femoral adipocytes. Taken together, these results suggest that for a given VAT deposition, the presence of hypertrophied subcutaneous abdominal adipocytes in men appears to be associated with further deterioration in the metabolic risk profile. On the other hand, the hypertrophy of femoral adipocytes does not further alter the metabolic complications generally related to obesity in both men and women.

Reduction of visceral adipose tissue during weight loss.

OBJECTIVE: The aims of the present study were to retrospectively: (1) compare how weight loss affects the reduction of adipose tissue from three different sites between men and women; and (2) to verify whether gender differences in the reduction of adipose tissue are influenced by changes in fat mass (FM) and initial levels of fat in different compartments. DESIGN: Double-blind randomized treatment with fenfluramine once daily coupled to a non-macronutrient specific energy restriction. SUBJECTS: Seventeen obese men (age 43.9+/-1.5 and body mass index (BMI) 34.3+/-0.7) and 17 obese women (age 41.2+/-1.2 and BMI 35.7+/-0.6). INTERVENTIONS: Subjects were given fenfluramine (60 mg) or placebo once daily and were also subjected to a non-macronurient specific energy restriction of -2.9 MJ/day (-700 kcal/day) for 15 weeks. RESULTS: Body weight, FM, fat-free mass (FFM), waist circumference, BMI, as well as visceral (VAT), subcutaneous abdominal (SAT) and thigh (TAT) adipose tissue were all significantly reduced. Men lost significantly more VAT (-41.6%) than SAT (-22.5%), or than TAT (-20.5%) while no site difference in fat loss was observed in women when changes were calculated as a percentage of initial levels. Men lost about twice as much fat from the VAT compartment than did women (P<0.05), even after having considered changes in FM as a potential covariate. In absolute values, TAT was reduced to a lesser extent in men than in women. However, when initial levels of respective fat depots were also taken into account, gender differences in VAT and TAT loss were no longer statistically significant. CONCLUSION: These results suggest that gender differences in VAT reduction during weight loss are independent of changes in FM. However, once initial levels of VAT are also taken into account, gender differences in the reduction of this tissue during weight loss are no longer apparent.

Persistent organic pollutants meet adipose tissue hypoxia: does cross-talk contribute to inflammation during obesity?

Lipophilic persistent organic pollutants (POPs) accumulate in lipid-rich tissues such as human adipose tissue. This is particularly problematic in individuals with excess adiposity, a physiological state that may be additionally characterized by local adipose tissue hypoxia. Hypoxic patches occur when oxygen diffusion is insufficient to reach all hypertrophic adipocytes. POPs and hypoxia independently contribute to the development of adipose tissue-specific and systemic inflammation often associated with obesity. Inflammation is induced by increased proinflammatory mediators such as tumour necrosis factor-alpha, interleukin-6, and monocyte chemotactic protein-1, as well as reduced adiponectin release, an anti-inflammatory and insulin-sensitizing adipokine. The aryl hydrocarbon receptor (AhR) mediates the cellular response to some pollutants, while hypoxia responses occur through the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF)-1. There is some overlap between the two signalling pathways since both require a common subunit called the AhR nuclear translocator. As such, it is unclear how adipocytes respond to simultaneous POP and hypoxia exposure. This brief review explores the independent contribution of POPs and adipose tissue hypoxia as factors underlying the inflammatory response from adipocytes during obesity. It also highlights that the combined effect of POPs and hypoxia through the AhR and HIF-1 signalling pathways remains to be tested.

Dietary practices in isolated First Nations communities of northern Canada: combined isotopic and lipid markers provide a good qualitative assessment of store-bought vs locally harvested foods consumption.

OBJECTIVE: In First Nations communities of northwestern Ontario, where rates of type 2 diabetes mellitus are some of the highest in the world, ascertaining wild food dietary practices is extremely challenging owing to seasonal availability, environmental factors, life circumstances and language/cultural barriers. The purpose of this study was to determine whether analysis of isotopic and fatty acid (FA) profiles could provide more comprehensive information to discriminate between three categories of wild food consumption (that is, plants and animals) in two isolated First Nations communities of northwestern Ontario. In addition, this analysis also highlights whether wild food consumption as practiced in these two communities can increase circulating levels of polyunsaturated FAs (PUFAs), which provide a number of important metabolic benefits that could impact the prevention/treatment of T2DM. RESULTS: (13)C enrichment (in expired CO2, plasma and hair), (15)N enrichment (in hair) and FA profiles in plasma phospholipids (phospholipid fatty acid (PL-FA)) were quantified in men and in women consuming various amounts of wild food. (13)C/(12)C ratios were lower and (15)N/(14)N ratios were higher in participants consuming wild food at least once a week. In addition, FA results indicated that the relative contributions of 20:4 Ω-6 and 22:6 Ω-3 to total PL-FAs were higher and 18:2 Ω-6 lower in wild food consumers. CONCLUSION: Together, these findings confirm that isotopic and lipid markers discriminate between the different wild food categories in these two First Nations communities. Knowing the close relationship between dietary intake and the potential role of PUFA in the prevention/treatment of obesity and obesity-related diseases, it is critical to accurately measure the composition of diet for individuals in their specific environments.

Weight loss and regain in obese individuals: a link with adipose tissue metabolism indices?

This study was performed to examine whether changes in subcutaneous adipose tissue (SCAT) metabolism indices after weight loss were related to the magnitude of weight regain. Nine men and ten premenopausal women whose body mass index ranged from 30 to 42 kg/m(2), 35-48 years old, were studied before and after a 15-week weight loss program, as well as at a 17-22-month follow-up period. Although body composition was evaluated at all study periods, abdominal and femoral SCAT-lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities, and α2- and ß-adrenoceptors (ARs) were measured before and after weight loss, exclusively. Although the SCAT-LPL activity did not change after weight loss in men, it tended to decrease in the femoral depot of women (p = 0.06). SCAT-HSL activity remained unchanged after weight reduction in men, while the post-weight loss lipase activity tended to be higher in both regions of women (p = 0.06). Although the post-weight loss number of ß-ARs was higher irrespective of the fat depot (0.001 < p < 0.05), the number of α2-ARs was increased in the femoral (p < 0.05), but not in the abdominal SCAT (p = 0.08) after weight reduction, in men. Neither the α2- nor the ß-AR density changed after weight reduction, in women. Abdominal SCAT-LPL activity after weight reduction was negatively related to weight regain indices, in women (-0.65 < Rhô < -0.75; 0.01 < p < 0.05). Both the post-weight loss abdominal SCAT α2-AR density and the α2-/ß-AR balance were positively associated with weight regain indices, in men (0.69 < Rhô < 0.88; 0.01 < p < 0.05). These results suggest that selected SCAT metabolism indices could predict failure to weight loss maintenance, in both genders.

The association of type 2 diabetes and insulin resistance/secretion with persistent organic pollutants in two First Nations communities in northern Ontario.

AIMS: Recent evidence suggests an association between persistent organic pollutants (POPs) and type 2 diabetes. In two First Nations communities where wild food is consumed by a large portion of the population, we compared pollutants in plasma between diabetic and non-diabetic individuals, and investigated the strength of association between pollutants and insulin resistance/secretion in non-diabetic individuals. METHODS: The study population consisted of 72 participants. Oral Glucose Tolerance Tests were used to assess diabetes status. Plasma was used to determine POP concentrations and mercury concentrations were determined from hair samples. RESULTS: Age-adjusted plasma concentrations of some pollutants were significantly higher in diabetic than in non-diabetic individuals. When taking into account age, adiposity levels, and smoking status, POP levels were not associated with insulin resistance nor with insulin secretion in non-diabetic individuals. CONCLUSIONS: These findings confirm that POP concentrations in plasma may be higher in diabetic than in non-diabetic individuals. No association was however seen between POP concentrations and markers of insulin resistance/secretion in non-diabetic individuals.

Effects of acute hyperinsulinaemia on total and high-molecular-weight adiponectin concentration in metabolically healthy but obese postmenopausal women: a Montreal-Ottawa New Emerging Team (MONET) study.

AIM: The aim of this study was to determine the differences and changes in total and high-molecular-weight (HMW) adiponectin levels among metabolically healthy but obese (MHO) postmenopausal women in response to acute hyperinsulinaemia. METHOD: In this cross-sectional study, 55 non-diabetic overweight and obese postmenopausal women underwent a hyperinsulinaemic-euglycaemic clamp test to evaluate insulin sensitivity. Subjects within the upper tertile of insulin sensitivity were described as 'MHO' (n=18), whereas those within the lowest tertile were considered 'at risk' (n=18). Plasma total and HMW adiponectin levels were measured by ELISA at 0 (baseline), 90, 160 and 180 min during the clamp. RESULTS: At baseline and at all time points during the clamp, MHO individuals had significantly higher total and HMW adiponectin levels than at-risk subjects (AUC: total adiponectin=2506 ± 1010 vs 1616 ± 830; HMW adiponectin=909 ± 307 vs 604 ± 349; P<0.05). In addition, a significant reduction in total adiponectin was observed at 160 min and 180 min in at-risk and MHO subjects, respectively, while HMW adiponectin significantly decreased at 160 min in at-risk subjects, and at 90 min as well as 160 min in MHO women. CONCLUSION: MHO postmenopausal women had higher levels of plasma total and HMW adiponectin than at-risk subjects at baseline and during the clamp. Furthermore, significant decreases in total and HMW adiponectin were observed at certain time points in both the MHO and at-risk subjects.

Physical activity and weight maintenance.

Physical activity is an important component of a weight-reducing program. When combined with a low fat diet, a physical activity program can reduce body weight by 10-15% in individuals complying with the program. However, even in disciplined individuals, resistance to lose fat ultimately occurs generally before the body composition status of the reduced-obese subjects is comparable to that of their lean counterparts. On the other hand, this weight loss is generally sufficient to normalize the risk profile regarding the development of diabetes and heart diseases. Therefore, this suggests that trying to lose weight beyond the threshold of spontaneous resistance to lose fat, may be unnecessary and not feasible. Furthermore, if one also considers the potential risks for health associated with large fat loss, it is probably not relevant to encourage further weight loss in reduced-obese individuals, when their metabolic profile is normalized. It is also important to emphasize that in such a context, the physical activity program must be maintained on a permanent basis to prevent body weight regain.

Acute effects of exercise on energy intake and feeding behaviour.

The main objective of the present study was to evaluate the short-term effects of exercise of different intensities on energy intake. Eleven young men were submitted to three randomly assigned sessions (one control and two exercise sessions) in which they ate, ad libitum, foods from a buffet-type meal. The energy cost of exercise was the same in the two exercise sessions. Results showed that there was no significant change in post-exercise subjective levels of hunger and fullness as well as total energy and macronutrient intakes in comparison with the control session. However, when energy intake relative to expenditure was considered by subtracting the surplus of energy expended during exercise from total energy intake, high-intensity exercise exerted a greater reducing effect on this variable compared with the control and low-intensity exercise sessions. These results suggest that for a given level of energy expenditure, high-intensity exercise favours negative energy balance to a greater extent than low-intensity exercise.

Thermogenesis and weight loss in obese individuals: a primary association with organochlorine pollution.

The main objective of this study was to investigate the potential impact of body organochlorine (OC) pollution on the adaptive change in thermogenesis induced by body weight loss. Fat mass (FM), fat-free mass (FFM), and sleeping metabolic rate (SMR) were measured in obese individuals before and after a weight-reducing program. The measured values of SMR were then compared to those predicted from a reference equation established from FM and FFM in control subjects. Plasma OC, leptin, total tri-iodothyronine, and free thyroxine concentrations were also measured in obese subjects before and after weight loss. After weight loss, the measured decrease in SMR was greater than that predicted by changes in FM and FFM. Increased plasma OC concentration was the factor explaining the greatest proportion of the difference between predicted and measured SMR changes induced by body weight loss. OC pollution seems to be a new factor affecting the control of thermogenesis in some obese individuals experiencing body weight loss.

beta-adrenoceptor-stimulated lipolysis of subcutaneous abdominal adipocytes as a determinant of fat oxidation in obese men.

BACKGROUND: To verify whether an impaired lipolytic capacity of subcutaneous adipocytes may contribute to low rate of fat oxidation. DESIGN: Relationships between adipose tissue lipolysis of subcutaneous (subc) abdominal and femoral isolated adipocytes and respiratory quotient (RQ) were investigated in 20 obese men (age: 44 +/- 5 years; means +/- SD) studied in a fasting state. RESULTS: Maximal isoproterenol-induced lipolysis was greater in subcutaneous abdominal than in femoral fat cells even if glycerol release was corrected for variation in cell surface area (P < 0.01). On the other hand, no regional variation was observed in the adipose cell lipolytic responses to postadrenoceptor agents such as dibutyryl-cyclic AMP, forskolin and theophylline. Maximal isoproterenol-induced lipolysis of subc abdominal, but not of femoral adipocytes, was inversely related to RQ (r = - 0.61; P < 0. 01) and positively associated to fat oxidation (r = 0.57; P < 0.01). These relationships were independent of possible confounding factors such as fat mass, fat-free mass, waist girth and subc abdominal adipose tissue accumulation assessed by computed tomography, as maximal isoproterenol-induced lipolysis of subcutaneous abdominal adipocytes was the only variable retained as a significant predictor of RQ levels (38% of variance) and of fat oxidation (30% of variance). CONCLUSION: These results suggest that adipose tissue lipolytic activity of subc abdominal adipocytes acts as a determinant of fat oxidation in obese men.