Obese Male Subjects Research Articles

Effect of a long-duration physical exercise on fat cell lipolytic responsiveness to adrenergic agents and insulin in obese men.

The aim of the study was to investigate whether a long-lasting bout of exercise modifies the lipolytic beta- and antilipolytic-alpha(2)-adrenergic effect and the antilipolytic effect of insulin in obese subjects. Biopsies of abdominal subcutaneous adipose tissue were performed before and immediately after 2 h exercise (at 50% of VO(2max)) on an ergometric bicycle. Nine healthy obese male subjects (mean age 38.0+/-3.5 y; mean body mass index (BMI) 35.6+/-3.9 kg/m(2)) were included in the experiment. :The lipolytic responsiveness to adrenaline, isoprenaline (beta-adrenergic agonist), UK-14304 (alpha(2)-adrenergic agonist) and insulin was studied in the isolated fat cell obtained by biopsies of subcutaneous adipose tissue from the peri-umbilical region before and after exercise. After exercise, an increase was observed in spontaneous lipolytic rate, and in the lipolytic effect of isoprenaline, but no modification in the lipolytic action of adrenaline. Antilipolytic effects of UK-14304 and insulin were not changed by the single bout of exercise. A single bout of long-term exercise increased the responsiveness of adipose tissue to beta-adrenergic stimulation of lipolysis in obese subjects.

High protein vs high carbohydrate hypoenergetic diet in treatment of obese normoinsulinemic and hyperinsulinemic subjects

This study tests the hypothesis that hyperinsulinemic (HI) obese subjects respond differently from normoinsulinemics (NI) to changes in composition of hypoenergetic diets. Twenty-seven obese male subjects, 13 HI and 14 NI, were fed for 4 weeks either a high protein (HP) or a high carbohydrate (HC) hypoenergetic diet providing 80% of their resting energy expenditure (REE). On the HP diet weight loss was significantly higher in HI as compared to NI group. Alternatively, the HI group lost less weight than NI group on the HC diet. The HC diets resulted in a considerable and similar reduction in REE in both HI and NI groups as opposed to the HP diet, which maintained REE in both HI and NI. A higher decrease and normalization of fasting insulin levels was observed in the HI group on the HP as compared to HC diet. In conclusion, hyperinsulinemic, in contrast to normoinsulinemic obese subjects, seem to achieve better weight reduction, less decline in energy expenditure, and normalization of insulin levels on HP than isocaloric HC diet.

The fate of [U-(13)C]palmitate extracted by skeletal muscle in subjects with type 2 diabetes and control subjects.

The current study investigated the fate of a [U-(13)C]palmitate tracer extracted by forearm muscle in type 2 diabetic and control subjects. We studied seven healthy lean male subjects and seven obese male subjects with type 2 diabetes using the forearm muscle balance technique with continuous intravenous infusion of the stable isotope tracer [U-(13)C]palmitate under baseline conditions and during intravenous infusion of the nonselective beta-agonist isoprenaline (ISO; 20 ng *kg(-1) lean body mass* min(-1)). In skeletal muscle of control subjects, there was a significant release of (13)C-labeled oxidation products in the form of (13)CO(2) (15% of (13)C uptake from labeled palmitate) and a significant release of (13)C-labeled glutamine (release of (13)C-labeled atoms from glutamine was 6% of (13)C uptake from labeled palmitate), whereas in type 2 diabetic subjects there was no detectable release of (13)CO(2) and (13)C-glutamine, despite a significant uptake of [U-(13)C]palmitate (60% of control value). There was net uptake of arterial (13)C-labeled glutamate by forearm muscle in both groups. Also, the ISO-induced increase in arterial glutamine enrichment and arterial concentration of (13)C-glutamine was more pronounced in the diabetic group relative to control subjects. In view of the diminished ISO-induced release of (13)C-glutamine from type 2 diabetic muscle, the latter data indicate that more [U-(13)C]palmitate entered the liver in the diabetic group and was incorporated into newly synthesized glutamine and glutamate molecules. Thus, the lack of release of (13)C-labeled oxidation products by type 2 diabetic muscle during beta-adrenergic stimulation, despite significant [U-(13)C]palmitate uptake, indicates differences in the handling of fatty acids between type 2 diabetic subjects and healthy control subjects.

Elevated plasma total homocysteine levels in hyperinsulinemic obese subjects

Homocysteine has been associated with the oxidative stress in the pathogenesis of atherosclerosis. Oxidative stress caused by triglycerides and free fatty acids is known to cause insulin resistance and hyperinsulinemia. On the other hand, insulin resistance may increase homocysteine levels. Since obesity is associated with insulin resistance and hyperinsulinemia, we aimed to study the possible association of homocysteine with hyperinsulinemia in obese subjects. 20 obese male subjects (body mass index >29), aged 33–55 (mean 45 years old) were studied. A fasting blood sample was obtained for the study and the subjects undertook an oral glucose tolerance test with samples taken at 1 and 2 h after glucose. Subjects were divided in two groups according to the fasting insulin levels, < 9 μU/ml or normoinsulinemic (group 1) and >9 μU/ml or hyperinsulinemic (group 2). Glucose, insulin, homocysteine, folate, B 12, total cholesterol, HDL-cholesterol and triglycerides levels were determined in fasting blood samples. In oral glucose tolerance test, glucose, insulin and homocysteine levels were measured. Hyperinsulinemic obese subjects (group 2) had higher levels of insulin and glucose at 1 h and 2 h postglucose, compared with group 1. Fasting total homocysteine and triglyceride levels were also increased in this group, whereas folate and B 12 levels were similar in both groups. Fasting homocysteine significantly correlated with fasting insulin (r = 0.6, p <0.01). Homocysteine levels slightly but significantly decreased after glucose loading in normoinsulinemic but not in hyperinsulinemic obese subjects. These results show that higher homocysteine levels are observed in the hyperinsulinemic obese subjects and suggest that homocysteine could play a role in the higher risk of cardiovascular disease in obesity.

Relation between body fat mass and lipid status in the obese working population

Obesity can be defined as an excessive accumulation of health threatening body fat, caused by positive energetic balance. It can be classified according to body mass index as normal body mass, excessive body mass, significant obesity and extreme obesity. According to WHR (waist-hip ratio), it can be classified to android and gynoid type depending on fat tissue distribution. Android type has greater frequency of cardiovascular and metabolic complications, as is occurrence of premature atherosclerosis. As metabolic complications we consider lipid status disorders in obese workers, and these complications are related to body composition. Among 331 workers, we separated 95 persons with BMI > 30 kg/m2. This group was classified according to gender, their body composition has been measured using bioelectrical impedance method and, subsequently, cholesterol, triglycerides, HDL and LDL levels were determined, searching for relationship of body composition with lipid status fractions p < 0.05. High body fatty was found in 33.03% of male and in 37.48% of female subjects. It was found that in male subjects cholesterol levels (6.70 mml/L), triglycerides (2.56 mml/L), limit values of LDL (3.93 mml/L) and limit values of HDL (1.16 mml/L) were highly risky. Positive insignificant relationship of body fatty mass with cholesterol, triglycerides, LDL, but not with HDL was found. Results point to highly risky limit values of lipid parameters in male and female subjects. These values can be explained by older age of subjects, their way of life and nutrition regimen, significant comorbidity in this group, and influence on working ability. It was found that obese male and female subjects have high values of body fatty mass. Male subjects have highly risky levels of lipid status fractions, while in female subjects these are limit values. Insignificant positive corelation of body fatty mass with lipid status fractions in tested population was found. The obtained results are significant regarding morbidity expectation and studies of complications of obese working population, as well as in judgment of working ability.

Plasma free Fatty Acid uptake and oxidation are already diminished in subjects at high risk for developing type 2 diabetes.

The objective of this study was to investigate to what extent disturbances in fatty acid metabolism found in type 2 diabetes are already present in subjects at high risk for developing diabetes (i.e., impaired glucose tolerance [IGT]). Components of fatty acid metabolism were measured in male subjects with IGT during postabsorptive conditions and during 60 min of exercise (50% VO(2max)) with the use of the stable isotope tracer [U-(13)C]palmitate in combination with indirect calorimetry, and those values were compared with previously published findings in male type 2 diabetic and male obese subjects. No differences were found between groups in energy expenditure and in total fat and carbohydrate oxidation. Rate of appearance and rate of disappearance of plasma free fatty acid (FFA) were lower in subjects with IGT and type 2 diabetes compared with obese subjects (P < 0.05). Plasma FFA oxidation was lower in subjects with IGT and type 2 diabetes compared with obese subjects at rest and tended to be lower during exercise (rest: 3.7 +/- 0.3, 4.4 +/- 0.6, and 6.9 +/- 1.0 micromol. kg fat-free mass [FFM](-1). min(-1), P < 0.01; exercise: 15.0 +/- 1.7, 14.1 +/- 1.9, and 19.6 +/- 1.5 micromol. kg FFM(-1). min(-1) for IGT, type 2 diabetic, and obese subjects, respectively, P = 0.07). Triglyceride-derived fatty acid oxidation, however, was elevated in subjects with IGT and type 2 diabetes during exercise (3.6 +/- 1.4, 1.4 +/- 1.4, and -4.0 +/- 2.0 micromol. kg FFM(-1). min(-1) for IGT, type 2 diabetic, and obese subjects, respectively; P < 0.05). These data demonstrate that male subjects with a prediabetic condition (IGT) have the same defects in fatty acid utilization as subjects with type 2 diabetes, suggesting that these disturbances may play an important role in the progression from IGT to type 2 diabetes.

The role of postprandial releases of insulin and incretin hormones in meal-induced satiety--effect of obesity and weight reduction.

Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects. To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake. Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3 h after the test meal. Nineteen non-diabetic obese (body mass index (BMI) 34.1--43.8 kg/m(2)) and 12 lean (BMI 20.4--24.7 kg/m(2)) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4--23.2). Total area under the GLP-1 response curve (AUC(total, GLP-1)) was lower in obese before and after the weight loss compared to lean subjects (P<0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P=0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUC(total, GIP) and AUC(incremental, GIP) were lowered (P<0.05). An inverse correlation was observed between AUC(incremental, GIP) and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r(2)=0.67, P=0.001). Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.

Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise.

The present study was intended to investigate the different components of fatty acid utilization during a 60-min period of moderate-intensity cycling exercise (50% of VO2max) in eight male type 2 diabetic subjects (aged 52.6 +/- 3.1 years, body fat 35.8 +/- 1.3%) and eight male obese control subjects (aged 45.1 +/- 1.4 years, body fat 34.2 +/- 1.3%) matched for age, body composition, and maximal aerobic capacity. To quantitate the different components of fatty acid metabolism, an isotope infusion of [U-13C]-palmitate was used in combination with indirect calorimetry. In separate experiments, the 13C label recovery in expired air was determined during infusion of [1,2-13C]-acetate (acetate recovery factor). There were no differences in energy expenditure or carbohydrate and total fat oxidation between the groups. The rate of appearance (Ra) of free fatty acid (FFA) (P < 0.05) and the exercise-induced increase in Ra of FFA were significantly lower (P < 0.05) in type 2 diabetic subjects compared with control subjects (baseline vs. exercise [40-60 min]; type 2 diabetes 11.9 +/- 0.9 vs. 19.6 +/- 2.2 micromol x kg(-1) fat-free mass [FFM] x min(-1) and control 15.8 +/- 1.8 vs. 28.6 +/- 2.1 micromol x kg(-1) FFM x min(-1)). The oxidation of plasma-derived fatty acids was significantly lower in type 2 diabetic subjects during both conditions (P < 0.05, baseline vs. exercise [40-60 min]; type 2 diabetes 4.2 +/- 0.5 vs. 14.1 +/- 1.9 micromol x kg(-1) FFM x min(-1) and control 6.2 +/- 0.6 vs. 20.4 +/- 1.9 micromol x kg(-1) FFM x min(-1)), whereas the oxidation of triglyceride-derived fatty acids was higher (P < 0.05). It is hypothesized that these impairments in fatty acid utilization may play a role in the etiology of skeletal muscle and hepatic insulin resistance.

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men.

The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.

Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans

Studies have shown evidence of production of nitric oxide (NO) in adipose tissue, as well as inhibition of lipolysis by NO. We have analyzed nitric oxide synthase (NOS) expression in subcutaneous adipose tissue from 13 nonobese and 18 obese male subjects. Using a competitive reverse transcription polymerase chain reaction method, endothelial (eNOS) and inducible (iNOS), but not neuronal (nNOS), nitric oxide synthase mRNA expression was detected in isolated fat cells and pieces of adipose tissue. Tissue mRNA levels for eNOS were 3,814 +/- 825 and 5,956 +/- 476 amol/mg RNA (P = 0.043), and for iNOS 306 +/- 38 and 332 +/- 48 amol/mg RNA, for nonobese and obese individuals, respectively. Western blotting revealed similar eNOS protein levels in isolated fat cells and adipose tissue pieces. Protein levels for eNOS in nonobese and obese individuals, respectively, were (in optical density [OD] units per mm(2) per 100 microgram of total protein) 0.11 +/- 0.08 and 2.80 +/- 1.30 (P = 0.043). iNOS protein was detectable, but not measurable, at low levels in a subset of obese patients (3 of 10). iNOS protein levels could not be detected in nonobese individuals. Hormone-sensitive lipase (HSL), the key regulating enzyme in lipolysis, is reduced in obesity. The expression of HSL protein in subcutaneous adipose tissue was studied in the same subset of patients; in agreement with previous results, HSL levels were reduced in obese subjects: 4.64 +/- 1.10 and 1.27 +/- 0.35 (P = 0.012) in nonobese and obese subjects, respectively. In conclusion, this study shows that eNOS and iNOS, but not nNOS, are present in human subcutaneous adipose tissue. Gene expression and protein levels of eNOS are increased, whereas HSL protein levels are decreased in obesity. It is speculated that increased NO production, preferably by eNOS, and decreased HSL levels may cause decreased subcutaneous adipose tissue lipolysis in obesity. synthases in subcutaneous adipose tissue of nonobese and obese humans.

Lipid Profiles of Obese Children and Adolescents Before and After Significant Weight Loss

Childhood obesity has been associated with elevated serum levels of total cholesterol, triglycerides, and low-density lipoproteins (LDLs). We observed the lipid profiles of obese female subjects versus obese male subjects before and after significant weight loss. We studied 29 girls and 21 boys enrolled in a multidisciplinary weight reduction program. Measures were taken at enrollment and at 10 weeks. Significant improvements were observed for changes in percentage of ideal body weight and total cholesterol and triglyceride levels. In addition, LDL decreased significantly in girls but not in boys. A combination of diet, behavior modification, and exercise, is an effective instrument for lowering total cholesterol and triglyceride levels in obese children. In addition, girls tend to be more susceptible to a decrease in LDL level, which might result in an increased cardiovascular protective effect.

Sympathetic modulation of lipolysis in subcutaneous adipose tissue: Effects of gender and energy restriction

To investigate the differences in the regulation of lipolysis between male and female obese subjects in vivo, we used an in situ microdialysis technique before and after 3 weeks of energy restriction. Using this method, we examined glycerol, glucose, and lactate responses after 5 minutes of epinephrine stimulation in the adipose tissues. Glycerol releases after the perfusion of phenfolamine, orciprenaline, and propranolol were also studied. Sixteen subjects were studied (8 men, 8 women, 35 to 45 years of age, body mass index 38 to 50 kg/m2). In women, epinephrine provoked a greater glycerol release than in men in both abdominal and femoral regions (P < .05). In men and women there was a significant decrease in the concentration of glucose and a significant increase in lactate concentration after epinephrine stimulation (P < .001). After 3 weeks of energy restriction, glycerol release after epinephrine stimulation was greater in both sexes than that observed before energy restriction (P < .05). Both phentolamine and orciprenaline stimulated the release of glycerol (P < .01); phentolamine had a higher effect in women, while propranolol had no effect on glycerol release in both sexes. In summary, we have demonstrated that epinephrine provoked a greater lipolytic response in obese women in both abdominal and femoral adipose tissues. The lipolytic response was further enhanced after 3 weeks of energy restriction in each gender. The decrease in glucose concentration suggests that glucose may be reutilized for synthesis into new triacylglycerol. Knowledge about the sensitivity to lipolytic agents in subcutaneous adipose tissue may provide potential new approaches for modulating the lipolytic responses of subcutaneous adipose tissue differently in men and women.

Endurance training increases the beta-adrenergic lipolytic response in subcutaneous adipose tissue in obese subjects.

The aim of this study was to assess, by longitudinal follow-up, the influence of aerobic training on the in vivo lipolytic activity of adipose tissue in obese male subjects. Eleven obese non-diabetic males, aged 41.5+/-5.77 (range 27-49 y) with body mass index (BMI) 36.5+/-4.5 kg/m2 (range 29.4-47.1 kg/m2) participated in the study. Subjects took part in a 12-week aerobic training program. Before and after training, microdialysis of abdominal subcutaneous adipose tissue (SCAT) was carried out, using perfusion with graded doses of the beta-adrenergic agonist isoprenaline and a single dose of the phosphodiesterase inhibitor theophylline. In addition, the response of plasma glycerol and free fatty acids (FFAs) to intravenous infusion of graded doses of isoprenaline was tested. The training did not induce significant weight loss and promoted an increase in maximum aerobic capacity (P<0.05). The increase of extracellular glycerol in SCAT in response to isoprenaline perfusion was enhanced after the training (P<0.05), while no change in the response of interstitial glycerol to theophylline action was observed. The training did not elicit a change in the isoprenaline-induced changes of blood flow in adipose tissue. The increases of plasma FFAs and glycerol in response to intravenous isoprenaline infusion, were significantly enhanced after training. The present study shows that aerobic training induced an increase in the response of plasma and subcutaneous adipose tissue concentration of glycerol to beta-adrenergic stimulation. The effect of an agent acting at the post-receptor level (theophylline) in SCAT was not modified by training.

Post-prandial chylomicron response may be predicted by a single measurement of plasma apolipoprotein B48 in the fasting state.

The clearance of chylomicron remnants was assessed in normolipaemic, dyslipidaemic and obese male subjects by monitoring the plasma kinetics of apolipoprotein (apo) B48, retinyl palmitate and triglyceride after a lipid meal. Regression analysis of fasting plasma apo B48 with the area under the post-prandial curves of apo B48, retinyl ester and triglyceride was carried out in order to determine whether the post-prandial response could be predicted by the fasting concentration of this exclusive chylomicron marker. Fasted subjects were given an oral fat load supplemented with retinyl palmitate, and blood samples were drawn over a 10-h period. Apolipoprotein B48 was determined by Western blotting in the plasma density fraction less than 1.063 g mL-1. Plasma retinyl palmitate and triglyceride were determined by high-performance liquid chromatography (HPLC) and colorimetric procedures respectively. The areas under the apo B48, retinyl ester and triglyceride curves were determined by integration. Relationships between the post-prandial response and the fasting concentration of apolipoprotein B48 were assessed using least-squares regression analysis. We found a strong positive relationship between the fasting plasma concentration of apo B48 and the post-prandial kinetics of apo B48. Similarly, there was a positive relationship of fasting apo B48 with the retinyl ester area under the curve. Collectively, the data suggested that chylomicron remnant kinetics can be predicted based on the fasting level of apo B48. There was also a significant but weaker relationship of fasting apo B48 with post-prandial triglyceride kinetics, consistent with removal of this lipid by hydrolytic mechanisms in addition to particle uptake. The fasting plasma concentration of apo B48 appeared to be a good surrogate marker for the degree of post-prandial lipidaemia and may circumvent the need for oral fat challenges. Moreover, in the fasting state apo B48 concentration is a marker of chylomicron remnants, which are considered to be the proatherogenic form of these intestinally derived lipoproteins.

Uncoupling protein-3 gene expression: reduced skeletal muscle mRNA in obese humans during pronounced weight loss.

Uncoupling protein-3 is a member of a protein family that serves to dissipate energy in the form of heat thereby modulating energy expenditure. Alternative processing of uncoupling protein-3 transcripts results in two mRNA species that encode a large and small protein, perhaps differing in functional activity. Since obesity is associated with disrupted energy homeostasis, we measured muscle mRNA expression in morbidly obese and lean subjects. The two uncoupling protein-3 mRNA species were quantified in muscle tissue using an RNase protection assay. Gene locus effects on mRNA expression were studied by quantitative allele-specific primer extension. In both obese and lean subjects, the mRNA species encoding the small protein isoform was twice as abundant as the mRNA species encoding the large protein isoform. Neither the total uncoupling protein-3 mRNA expression nor the molar abundance ratios of the two mRNA species differed between obese and lean male or female subjects. Women who had lost 37+/-22 kg of weight in response to dietary restriction and continued a hypocaloric diet displayed lower mRNA than obese (p<0.005) or lean women (p<0.05). Primer extension assays in lean and obese subjects showed similar allelic mRNA abundance in all but one subject studied. Muscle expression of the two uncoupling protein-3 mRNA species is similar in obese and lean people. In obese patients, prolonged hypocaloric diet downregulates uncoupling protein-3 mRNA expression in muscle and can thereby enhance its energy efficiency. Sequence substitutions at the gene locus may only be minor determinants of mRNA expression in muscle tissue.

Effect of exercise training on long-term weight maintenance in weight-reduced men

This study investigated whether endurance training is effective for successful long-term weight maintenace after weight reduction. Fifteen male obese subjects (age, 37.3 ± 5.2 years; body weight [BW], 96.2 ± 13.6 kg; body mass index [BMI], 30.9 ± 2.8 kg · m −2) participated in a 16-month exercise-intervention study. During the first 4 months, all subjects trained three to four times weekly, consuming a very-low-energy diet (VLED) during the first 2 months. After the 4-month treatment period, seven subjects continued training for 12 months (3 to 4 times per week). The other eight subjects served as a control group not involved in a training program. The regain (increase during the intervention period as a percentage of the 4-month treatment) of BW at 16 months was 64% (±26%) for the whole group (trained v control, 52% ± 28% v 74% ± 20%, P = .09). The increase in absolute fat mass (FM) was significantly lower at 16 months for the trained group (trained v control, 4.8 ± 1.9 v 9.0 ± 3.3 kg), as was the regain of FM at 16 months (trained v control, 61% ± 24% v 92% ± 32%, P = .05). The amount of regain of the waist circumference, waist to hip ratio (WHR), and sagittal diameter were correlated with the amount of training (hours) performed weekly (Δwaist, r = − .55, P < .05; ΔWHR, r =−.50, P = .06; Δsagittal diameter, r = −.53, P < .05). Physical fitness parameters (maximal power output [Wmax] and oxygen uptake [Vo 2 max]) were significantly increased in both groups at 4 months. Trained subjects maintained high levels of physical fitness at 16 months, in contrast to the control group. In conclusion, although BW regain was not significantly different between the groups, trained subjects showed less regain of FM and higher levels of physical fitness, factors related to a lower risk for cardiovascular disease (CVD), compared with the control group. Furthermore, the regain of FM, which occurred even in the exercising group with a relatively intensive training program, suggests that maintenance of fat loss is extremely difficult.

Endurance training changes in lipolytic responsiveness of obese adipose tissue.

The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 +/- 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30-45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass (P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training (P < 0.05). The lipolytic effects of epinephrine, isoprenaline (beta-adrenoceptor agonist), and dobutamine (beta1-adrenoceptor agonist) were significantly increased (P < 0.05) but not those of procaterol (beta2-adrenoceptor agonist). The antilipolytic effects of alpha2-adrenoceptor and insulin were significantly decreased (P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of beta-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

Dyspnea in Obese Healthy Men

To determine whether obese, apparently healthy individuals experience dyspnea at rest and, if so, whether their pulmonary function test (PFT) profile and maximal respiratory pressures are different from obese, healthy subjects without dyspnea. Prospective, open. Pulmonary function test laboratory, Veterans Administration Medical Center. Twenty-three obese male subjects (each with a body mass index [BMI] of > 28 kg/m2) with an FEV1 level and an FEV1/FVC ratio > or = 80% of predicted and no coexisting conditions. Fifteen complained of dyspnea, where eight denied having it, at rest. Standard PFT parameters and maximum static inspiratory (P(Imax)) and expiratory (P(Emax)) mouth pressures were determined. Subjects with dyspnea had similar age and height but larger body weight (113.9+/-5.0 vs 97.4+/-2.6 kg, p = 0.03) and BMI (37.4+/-1.6 vs 31.8+/-0.7 kg/m2, p = 0.02) than subjects without dyspnea, and a greater number of them were current or previous smokers. Forced expiratory flow at 75% vital capacity (54.9+/-6 vs 75.5+/-7% predicted, p = 0.05), maximum voluntary ventilation (MVV; 90.2+/-3.8 vs 107.8+/-9.3% predicted, p = 0.05), and P(Emax) (77+/-2 vs 97.8% predicted, p = 0.007) were significantly reduced in the group of subjects with dyspnea. Large airway function (FVC, FEV1, and FEV1/FVC ratio), lung volumes, and gas exchange parameters were similar between the two groups. Some obese, but otherwise healthy, individuals experience dyspnea at rest. Reduced P(Emax) and MVV combined with greater body mass and peripheral airway disease are most likely responsible for the sensation of dyspnea in these individuals.

Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: Visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity

We investigated the relationship between uric acid (UA) metabolism and fat distribution in 36 obese men with a mean ± SD age of 38 ± 16 years and mean body-mass index (BMI) of 34 ± 4 kg/m 2. Subjects were divided into two groups: subcutaneous fat obesity (SFO) and visceral fat obesity (VFO), according to their abdominal fat distribtion based on the results of computed tomography (CT). SFO was defined as having a ratio of visceral fat area (VFA) to subcutaneous fat area ( V S ) of less than 0.4, and VFO was defined as having a V S ratio ≥ 0.4. The levels of serum total cholesterol (T-Chol), triglyceride (TG), and fasting plasma glucose (FPG), and the diastolic blood pressure (dBP) were significantly higher in the VFO group than in the SFO group. Serum UA levels were much higher in both the SFO and VFO groups than in the non-obese control group (492 ± 107 and 474 ± 90 v 309 ± 48 μmol/L, respectively). The 24-hour urinary urate excretion (u-UA24h) and the UA clearance (Cua) to creatinine clearance (Ccr) ratio were significantly higher in the VFO group than in the SFO group (3.75 ± 1.43 v 2.69 ± 1.12 mmol/d, P < .05; and 5.9% ± 2.0% v 3.6% ± 1.7%, P < .001, respectively). The frequency of hyperuricemia was markedly higher in both the SFO and VFO groups compared with the control group (71% and 73% v 0%, respectively). Although the high serum UA level seemed to be related to low u-UA24h in 80% of SFO subjects with hyperuricemia, this was the case in only 10% of VFO subjects. While 44% of VFO subjects with hyperuricemia were designed as an overproduction type. These results suggest that the mechanism of hyperuricemia in obesity may be affected by the difference in body fat distribution and that the assessment of body fat distribution and types of hyperuricemia is crucial for the treatment of obese patients with hyperuricemia.

Uncoupling protein-2 gene: reduced mRNA expression in intraperitoneal adipose tissue of obese humans.

The mitochondrial uncoupling protein-2 (UCP-2) is a recently discovered homologue of the brown adipose tissue-specific uncoupling protein and could be involved in the regulation of energy balance. Since obesity is associated with disturbed energy homeostasis, we tested the hypothesis that UCP-2 gene expression is deficient in this disorder. We determined, by a competitive reverse transcription-polymerase chain reaction assay, UCP-2 mRNA expression in intra- and extraperitoneal adipose tissues of 107 morbidly obese subjects and 31 lean control subjects. In both obese and non-obese subjects, UCP-2 mRNA abundance was higher in the intraperitoneal than in the extraperitoneal tissue (p < 0.05), but no association was observed between intra- and extraperitoneal expression in either group. Compared with lean control subjects, both male and female obese subjects displayed significantly lower average UCP-2 mRNA expression in the intraperitoneal adipose tissue (p < 0.006), while UCP-2 mRNA abundance in extraperitoneal adipose tissue was not different between obese and non-obese men and women. Intraperitoneal UCP-2 mRNA remained low in nine obese subjects who lost 23 +/- 12 kg of weight over a period of 10 +/- 5 months subsequent to weight reducing surgery. These data support the concept that impaired adipose tissue expression of UCP2 may play a role in the pathophysiology of obesity.