The effects of exercise, training on body composition and metabolism in men and women

In order to examine whether there are sex-differences in the response of energy balance to physical training slightly obese men and women participated in the same 3 months physical training program with the same individual relative intensity. The men became somewhat lighter (-2 kg) and leaner (-2.9 kg body fat) and showed decreases in sum of insulin and sum of C-peptide values during an oral glucose tolerance test as well as cholesterol values. The women showed decrease of 2.6 kg body fat, and also increased lean body mass (1.9 kg) and similar metabolic changes. The women had, however, a larger body fat mass at the outset. When women with similar body fat mass as that of men were analysed separately, no change in body weight or body fat had occurred, and the metabolic adaptations were less pronounced. No compensatory increase of energy intake could be discovered in any of the groups, the most obese women actually showed a decrease. Taken together with previous information these results suggest that men, like male rats, become leaner during physical training due to a lack of energy intake compensation. Women with similar body fat mass, however, like female rats, may react with such a compensation, causing a protection of their body fat. Women usually have more body fat than men, however. Obese women in this study showed a decrease of body fat.     

Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = -0.22), or physical activity energy expenditure (r = -0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 +/- 0.14 vs. 0.66 +/- 0.28 mmol/kg x min; P < 0.05). Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.     

Decreased Skeletal Muscle Potassium in Obesity

ABSTRACT The effect of body weight on total body potassium, skeletal muscle electrolytes and fat content was studied in seven lean and seven obese middle-aged men and seven lean and eight obese middle-aged women. Total body potassium and total body fat increased with body weight (p<0.01 and <0.05 for men, and p<0.05 and p<0.001 for women, respectively). So did muscle fat in men (p<0.01), while muscle tissue potassium was decreased in both obese men (p<0.001) and obese women (p<0.05). The skeletal muscle Na/K-ratio tended to be higher in obese men (p<0.1) but was not related to body weight in women. Skeletal muscle magnesium was higher (p<0.01) in obese men than in lean men. No differences between lean and obese women were found. Obese men had higher diastolic blood pressure (p<0.05) than lean men, while there was no difference between obese and lean women. Compared with lean subjects, obese subjects thus had lower relative skeletal muscle mass and men, especially, had more fat and less potassium in the skeletal muscle.     

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.     

Cellularity in different regions of adipose tissue in young men and women

Body cell mass, body fat, and total number of fat cells were determined in young men and women. In addition, regional determinations of adipose tissue thickness, fat cell size, and fat cell number were also performed. The individuals studied were 11 male and 12 female medical students with a mean age of 22 yr. In order to avoid deviations from ideal body weights, the individuals were preselected by using anthropometric standards. The women had more body fat than the men, which was due to an increase in the total number of fat cells. Mean fat cell size did not differ significantly between sexes. The women had greater adipose tissue thickness than the men, which was primarily due to an increase in local fat cell number in all regions investigated (epigastric, hypogastric, femoral, and gluteal) except in the gluteal region, where the difference was mainly explained by larger fat cells in women. When expressed in per cent of maximum values, the intrasexual patterns of adipose tissue thickness and local fat cell number in different regions were similar in men and women, while the pattern concerning fat cell size was slightly different between the sexes. There were no differences between sexes in cholesterol, triglyceride, fasting blood sugar, or fasting insulin values. Middle-aged randomly selected men and women examined previously had a larger amount of body fat than the young men and women, respectively, examined in the present investigation. This difference in body fat with age was due to a larger mean fat cell size in the middle-aged populations, while there was no difference in total fat cell number.     

Glucose tolerance and hyperinsulinaemia in obese women: role of adipose tissue distribution, muscle fibre characteristics and androgens

The separate independent statistical contribution of abdominal distribution of fat, hyperandrogenicity and muscle morphology to glucose intolerance and hyperinsulinaemia was analysed in 88 obese women. In univariate analyses the waist/hip circumference ratio (WHR), body fat and lean body mass were all positively associated, and SHBG levels were negatively associated with insulin and glucose values. Muscle fibre areas were positively correlated with insulin but not with glucose concentrations. Adjustment for other variables did not remove the positive association between WHR and fasting insulin and glucose concentrations. SHBG, free testosterone and type IIb fibre areas were, however, significant confounding factors in the relationship between WHR and summed insulin and glucose concentrations. We conclude that fat distribution in obese women is associated with fasting hyperglycaemia and hyperinsulinaemia, independently of androgens and muscle fibre morphology, but that reduced SHBG concentrations and increased type IIb fibre areas may partly explain increased glucose and insulin responses to an oral glucose load in abdominally obese women.     

Adipose tissue distribution changes during rapid weight loss in obese adults.

Changes in adipose tissue distribution as defined by the waist-to-hip ratio (WHR), were evaluated in 16 android, obese subjects (seven male and nine female) given a very low energy ketogenic diet of 1.72 MJ (411 kcal) for 4 weeks. Total weight loss was significantly greater for the males (11.2 +/- 2.5 kg) compared to females (8.3 +/- 0.8 kg); the relative weight loss however, was similar (9.9 vs 9.3 percent). Female and male losses in percent body fat and lean body mass were not significantly different. For both groups, significant (P less than 0.01) changes in waist and hip circumferences were observed; however, no significant changes were observed in WHR. These results indicate that in obese android male and female subjects, adipose tissue distribution as measured by WHR, does not change in response to rapid weight loss.     

Metabolic correlates of nonalcoholic fatty liver in women and men

Nonalcoholic hepatic steatosis associates with a clustering of metabolic risk factors and steatohepatitis. One risk factor for hepatic steatosis is obesity, but other factors likely play a role. We examined metabolic concomitants of hepatic steatosis in nonobese and obese men and women. Sixty-one obese women and 35 obese men were studied; both those with and without hepatic steatosis were compared against each other and against nonobese controls (17 women and 32 men) without hepatic steatosis. Obesity (defined as >or=25% body fat in men and >or=35% in women), was identified by x-ray absorptiometry, whereas hepatic steatosis (>or=5.5% liver fat) was detected by magnetic resonance spectroscopy. The primary endpoint was a difference in insulin sensitivity. Obese groups with and without steatosis had similar body fat percentages. Compared with obese women without hepatic steatosis, those with steatosis were more insulin resistant; the same was true for men, although differences were less striking. Obese subjects with hepatic steatosis had higher ratios of truncal-to-lower body fat and other indicators of adipose tissue dysfunction compared with obese subjects without steatosis. CONCLUSION: These results support the concept that obesity predisposes to hepatic steatosis; but in addition, insulin resistance beyond that induced by obesity alone and a relatively high ratio of truncal-to-lower body fat usually combined with obesity to produce an elevated liver fat content.     

Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss

The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance. To that end, we compared: 1) serum concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), and leptin in eight healthy lean control females and in android obese female without (n = 14) and with (n = 7) type 2 diabetes; and 2) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet (VLCD). As compared with lean controls, obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin, IL-6, TNFalpha, and C-reactive protein. In the whole group, IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values. VLCD resulted in weight loss and decreased body fat mass (approximately 3 kg). Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels. In contrast, VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum. These results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production. The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients.     

Adipose tissue oxygenation is associated with insulin sensitivity independently of adiposity in obese men and women

Adipose tissue (AT) dysfunction contributes to the pathophysiology of insulin resistance and type 2 diabetes. Previous studies have shown that altered AT oxygenation affects adipocyte functionality, but it remains to be elucidated whether altered AT oxygenation is more strongly related to obesity or insulin sensitivity. In the present study, we tested the hypothesis that AT oxygenation is associated with insulin sensitivity rather than adiposity in humans. Thirty‐five lean and obese individuals (21 men and 14 women, aged 40‐65 years) with either normal or impaired glucose metabolism participated in a cross‐sectional single‐centre study. We measured abdominal subcutaneous AT oxygenation, body composition and insulin sensitivity. AT oxygenation was higher in obese insulin resistant as compared to obese insulin sensitive (IS) individuals with similar age, body mass index and body fat percentage, both in men and women. No significant differences in AT oxygenation were found between obese IS and lean IS men. Moreover, AT oxygenation was positively associated with insulin resistance (r = 0.465; P = .005), even after adjustment for age, sex and body fat percentage (standardized β = 0.479; P = .005). In conclusion, abdominal subcutaneous AT oxygenation is associated with insulin sensitivity both in men and women, independently of adiposity. AT oxygenation may therefore be a promising target to improve insulin sensitivity.     

Metabolism of adipose tissue in intraabdominal depots in severely obese men and women

In groups of obese men and women with an abdominal type of fat distribution, we measured fat cell size, lipoprotein lipase (LPL) activity and lipolysis stimulated by norepinephrine (NE) or isoproterenol (ISO) or inhibited by insulin, in subcutaneous abdominal and retroperitoneal (nonportal), as well as in omental and mesenteric (portal) adipose tissues. Both men and women had large intraabdominal adipocytes. No differences were found between the two groups of obese subjects in fat cell size or LPL activity in the different adipose tissue regions. Women had as high NE- or ISO-stimulated lipolysis in the portal as in nonportal fat tissues, equally high as that found in men. In comparisons with a previous study in nonobese men and women, these results show an increased fat cell size in all tissues in obese women and an increased lipolysis in portal tissues in obese women and in nonportal tissues in obese men. Taken together, these results might mean that obese men and abdominally obese women have a large potential to release free fatty acids (FFA) from intraabdominal depots. This might be followed by metabolic derangements seen in such groups of obese subjects.     

De novo lipogenesis in adipose tissue of lean and obese women: application of deuterated water and isotope ratio mass spectrometry

OBJECTIVE: To evaluate the feasibility of using deuterated water and isotope ratio mass spectrometry to measure de novo fatty acid synthesis in adipose tissue, and to compare this parameter in obese and lean women. SUBJECTS: Six lean and six obese premenopausal Caucasian women in the main study and three obese Pima Indians in a pilot study. MEASUREMENTS: Deuterated water was administered orally twice daily for 14 days to create stable deuterium enrichment in body water, during which series of blood samples were collected to measure body water deuterium enrichment and deuterium incorporation into plasma total Triacylglycerol (TG) fatty acids and total cholesterol. Subcutaneous fat at different sites were sampled at the beginning and the end of deuterium administration to measure deuterium incorporation into TG fatty acids. RESULTS: Fractional de novo synthesis rate of TG fatty acids in adipose tissue was 0. 014+/-0.005 and 0.014+/-0.007% in lean and obese Caucasian women, corresponding to 2+/-0.7 and 5.6+/-3.2 g (P=0.3) of fatty acids synthesized daily, respectively. Plasma TG fatty acids and cholesterol synthesis rates were comparable to those reported previously. A pilot study showed that de novo lipid synthesis in adipose tissue of obese Pima Indians was also quantitatively minor. CONCLUSION: Human adipose tissue, like the liver, does not make a major contribution to whole body lipogenesis under eucaloric conditions. A combination of deuterated water and isotope ratio mass spectrometry is a useful research tool for studying accumulation of de novo synthesized lipids in human adipose tissue.     

CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity

BACKGROUND/AIMS: Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined. METHODS: sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression. RESULTS: Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression. CONCLUSION: Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.     

Age-related changes in fat deposition in mid-thigh muscle in women: relationships with metabolic cardiovascular disease risk factors

OBJECTIVE: To determine if fat deposition within mid-thigh muscle, represented by low density lean tissue density, is associated with age, low physical fitness, hyperleptinemia, hyperinsulinemia and dyslipidemia in women. SUBJECTS: Seventy-two women aged 18-69y with a wide range of total body fat (10-55%) and maximal aerobic capacity (VO2max: 17-61 ml/kg(-1)/min(-1)). MEASUREMENTS: Mid-thigh muscle, mid-thigh fat, low density lean tissue, intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal fat (by computed tomography, CT), fat mass (FM) and fat-free mass (FFM) (by dual energy x-ray absorptiometry, DEXA), plasma insulin and leptin (by radioimmunoassay, RIA) and lipoprotein lipid profiles (by enzymatic methods). RESULTS: VO2max declined with age (r=-0.59, P<0.0001) while IAAT and subcutaneous abdominal fat increased with age (r=0.68, r=0.57, r=0.63, P<0.0001). Mid-thigh low density lean tissue correlated with age (r=0.52), VO2max (r=-0.56), FFM (r=0.35), fat mass (r=0.68), IAAT (r=0.66) and subcutaneous abdominal fat (r=0.67, all P<0.005). Mid-thigh low density lean tissue also correlated with fasting plasma leptin, insulin, triacylglycerol (TG), total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels (r=0.44, 0.34, 0.41, 0.50, 0.53, respectively, all P<0.005), but not after controlling for body fat and age. Subcutaneous abdominal fat, IAAT, FFM and age were independent predictors of low density lean tissue (P<0.05). CONCLUSIONS: Mid-thigh low density lean tissue is directly related to age and adiposity. Furthermore, it appears that fat accretion in skeletal muscle adversely influences plasma insulin and lipoprotein metabolism in women, but not independently of total adiposity and age.     

Mechanisms underlying the metabolic actions of testosterone in humans: A narrative review

The role of testosterone in improving sexual symptoms in men with hypogonadism is well known. However, recent studies indicate that testosterone plays an important role in several metabolic functions in males. Multiple PubMed searches were conducted with the use of the terms testosterone, insulin sensitivity, obesity, type 2 diabetes, anaemia, bone density, osteoporosis, fat mass, lean mass and body composition. This narrative review is focused on detailing the mechanisms that underlie the metabolic aspects of testosterone therapy in humans. Testosterone enhances insulin sensitivity in obese men with hypogonadism by decreasing fat mass, increasing lean mass, decreasing free fatty acids and suppressing inflammation. At a cellular level, testosterone increases the expression of insulin receptor β subunit, insulin receptor substrate-1, protein kinase B and glucose transporter type 4 in adipose tissue and adenosine 5′-monophosphate-activated protein kinase expression and activity in skeletal muscle. Observational studies show that long-term therapy with testosterone prevents progression from prediabetes to diabetes and improves HbA1c. Testosterone increases skeletal muscle satellite cell activator, fibroblast growth factor-2 and decreases expression of the muscle growth suppressors, myostatin and myogenic regulatory factor 4. Testosterone increases haematocrit by suppressing hepcidin and increasing expression of ferroportin along with that of transferrin receptor and plasma transferrin concentrations. Testosterone also increases serum osteocalcin concentrations, which may account for its anabolic actions on bone. In conclusion, testosterone exerts a series of potent metabolic effects, which include insulin sensitization, maintenance and growth of the skeletal muscle, suppression of adipose tissue growth and maintenance of erythropoiesis and haematocrit.     

The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes

BACKGROUND: Long-chain fatty acids (LCFAs) cross the plasma membrane via a protein-mediated mechanism involving one or more LCFA-binding proteins. Among these, FAT/CD36 has been identified as key LCFA transporter in the heart and skeletal muscle, where it is regulated acutely and chronically by insulin. In skeletal muscle, FAT/CD36 expression and/or subcellular distribution is altered in obesity and type 2 diabetes. There is limited information as to whether the expression of this protein is also altered in subcutaneous and/or visceral adipose tissue depots in human obesity or type 2 diabetes. OBJECTIVES: To compare (a) the expression of FAT/CD36 in subcutaneous and visceral adipose tissue depots in lean, overweight, and obese individuals and in type 2 diabetics, (b) to determine whether the protein expression of FAT/CD36 in these depots is associated with the severity of insulin resistance (type 2 diabetes>obese>overweight/lean) and (c) whether FAT/CD36 protein expression in these adipose tissue depots is associated with alterations in circulating substrates and hormones. SUBJECTS: Subjects who were undergoing abdominal surgery and who were lean (n=10; three men, seven women), overweight (n=10; three men, seven women) or obese (n=7; one man, six women), or who had been diagnosed with type 2 diabetes (n=5; one man, four women) participated in this study. MEASUREMENTS: Subcutaneous and visceral adipose tissue samples, as well as blood samples, were obtained from the subjects while under general anesthesia. Adipose tissue samples were analyzed for FAT/CD36 using Western blotting. Serum samples were analyzed for glucose, insulin, FFA and leptin. BMI was also calculated. RESULTS: Subcutaneous adipose tissue FAT/CD36 expression was upregulated by +58, +76 and +150% in overweight, obese and type 2 diabetics, respectively. Relative to subcutaneous adipose tissue, visceral adipose tissue FAT/CD36 expression was upregulated in lean (+52%) and overweight subjects (+30%). In contrast, in obese subjects and type 2 diabetics, no difference in FAT/CD36 protein expression was observed between their subcutaneous and visceral adipose tissue depots (P>0.05). The subcutaneous adipose tissue FAT/CD36 expression (R=0.85) and the visceral adipose tissue FAT/CD36 expression (R=0.77) were associated with alteration in BMI and circulating glucose and insulin. CONCLUSIONS: Subcutaneous adipose tissue FAT/CD36 expression is upregulated in obesity and type 2 diabetes. As FAT/CD36 expression is not different in lean, overweight and obese subjects, and was only increased in type 2 diabetics, it appears that visceral adipose tissue FAT/CD36 may respond in a less dynamic manner to metabolic disturbances than subcutaneous adipose tissue FAT/CD36.     

Relationship between hormone replacement therapy use with body fat distribution and insulin sensitivity in obese postmenopausal women.

The aim of this study was to compare the effect of hormone replacement therapy (HRT) on insulin resistance and central adiposity in obese postmenopausal women. Forty-five obese postmenopausal women (16 HRT users and 29 nonusers), with a mean age of 56.6 +/- 5.3 years and duration of current, continuous HRT use of 4.7 +/- 2.9 years, were included in the study. Subjects were studied using oral glucose tolerance tests, euglycemic clamping, dual photon x-ray absorptiometry, computed tomography, doubly labeled water, and treadmill testing. Insulin sensitivity, total fat, visceral fat, subcutaneous abdominal fat, thigh muscle attenuation, daily physical activity energy expenditure, peak oxygen consumption (Vo(2)) were measured. HRT users had lower body weight (88.0 +/- 11.0 v 98.2 +/- 15.0 kg, P =.05), lower body mass index (33.1 +/- 3.5 v 36.8 +/- 5.2 kg/m(2), P =.05), lower fat mass (38.3 +/- 7.3 v 44.1 +/- 10 kg, P =.05), less visceral adipose tissue (157 +/- 47 v 211 +/- 81 cm(2); P =.05), and higher peak Vo(2) (21.1 +/- 4.6 v 17.6 +/- 2.2 mL/kg/min, P =.001) than nonusers. After adjustment for total fat, we noted a trend for decreased visceral adipose tissue in HRT users (P =.09). After adjustment for peak Vo(2), the decreased visceral adipose tissue persisted in HRT users (P <.01). Insulin sensitivity per kilogram of lean body mass did not differ between HRT users (0.51 +/- 0.22 mmol/kg/min) and nonusers (0.49 +/- 0.22 mmol/kg/min). It was concluded that obese postmenopausal women using HRT have a more favorable body composition and fat distribution pattern than nonusers. Although visceral adipose tissue is decreased in HRT users, insulin sensitivity does not differ between HRT users and nonusers.     

Plasma acylation stimulating protein concentration and subcutaneous adipose tissue C3 mRNA expression in nondiabetic and type 2 diabetic men

We studied the effect of an oral fat load on plasma acylation stimulating protein (ASP) concentrations in 9 lean healthy (age 59+/-2 years, body mass index [BMI] 23.2+/-0.4 kg/m(2); both mean+/-SEM), 9 obese nondiabetic (58+/-2 years, BMI 29.4+/-0.5 kg/m(2)), and 12 type 2 diabetic (60+/-2 years, BMI 29.6+/-1.0 kg/m(2)) men. Because ASP is a cleavage product of complement protein C3 (C3adesArg) and its secretion is regulated by insulin, we also examined the subcutaneous adipose tissue expression of C3 mRNA before and after a 240-minute euglycemic hyperinsulinemic clamp in a subgroup of these men. Plasma ASP concentration and adipose tissue C3 mRNA expression were higher in the obese groups than in the lean men. Plasma ASP concentration did not change significantly after the fat load. Fasting plasma ASP concentration and C3 mRNA expression were correlated negatively with insulin sensitivity and positively with the magnitude of postprandial lipemia in nondiabetic but not in type 2 diabetic men. The expression of C3 mRNA was not regulated by insulin. These data suggest that ASP is associated with whole-body glucose and lipid metabolism in nondiabetic individuals, whereas metabolic disturbances in diabetes may overcome the regulatory role of ASP in lipid and glucose metabolism.     

Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity

Obesity is related to the risk for developing non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and cardiovascular disease. Visceral adipose tissue (VAT) has been proposed to mediate these relationships. Abdominal subcutaneous adipose tissue (SAT) is divided into 2 layers by a fascia, the fascia superficialis. Little is known about the radiologic anatomy or metabolic correlates of these depots. The objective of this study was to relate the amounts of VAT, SAT, deep subcutaneous abdominal adipose tissue (DSAT), and superficial subcutaneous abdominal adipose tissue (SSAT) to gender and the metabolic complications of obesity after adjusting for total body fat and to discuss the implications of these findings on the measurement of adipose tissue mass and adipose tissue function. The design was a cross-sectional database study set in a nutrition research center. Subjects included 199 volunteers participating in nutrition research protocols who also had computed tomography (CT) and dual energy x-ray absorptiometry (DEXA) measurement of body fat. The amount of DSAT was sexually dimorphic, with women having 51% of the subcutaneous abdominal fat in the deep layer versus 66% for men (P <.05). Abdominal fat compartments were compared with metabolic variables before and after adjusting for body fat measured by DEXA using 2 separate methods. The unadjusted correlation coefficients between the body fat measures, R(2), were largest for fasting insulin and triglyceride and smaller for high-density lipoprotein (HDL) cholesterol and blood pressure. A large portion of the variance of fasting insulin levels in both men and women was explained by total body fat. In both men and women, the addition of VAT and subcutaneous abdominal adipose tissue depots only slightly increased the R(2). In men, when body fat compartments were considered independently, DSAT explained a greater portion of the variance (R(2) =.528) in fasting insulin than VAT (R(2) =.374) or non-VAT, non-DSAT subcutaneous adipose tissue (R(2) =.375). These data suggest that total body fat is a major contributor to the metabolic sequelae of obesity, with specific fat depots, VAT, and DSAT also making significant contributions.     

Effects of age, sex, and clinical conditions on adipose tissue cellularity in man

Methods for measurements of fat cell size in man are now available. Total fat cell number is more difficult to measure, and the numbers reported should probably so far be regarded as estimates of fat-containing fat cells. The first years of life seem to be critical for adipose tissue development in man. Nonobese adult women probably have more fat cells than men. Fat cell size increases with age.Obese children and adults show increases in both fat cell size and number. Division of obese subjects into different subgroups according to adipose tissue cellularity must take into consideration the age and sex variations in the nonobese population. Attempts to such subdivision seem to give one group with an increased number of fat cells, early debut of obesity, and increased body cell mass. These patients are difficult to treat successfully by conventional methods. Adult onset obesity seems to be characterized by enlarged fat cells.All data presently available are transsectional and do not allow any definite conclusions about possible fat cell division. Thus, there might well be adult obese subjects who, like certain genetically obese rodents, have fat cells which multiply during an abnormally long period of life.Fat cell size has been found to correlate with plasma insulin and triglyceride concentrations. Patients with endogenous hypertriglyceridemia and possibly adult onset diabetes mellitus before debut of the diabetes have enlarged fat cells, while patients with juvenile, insulin-requiring diabetes mellitus have small fat cells.Thus, the subgrouping of obesity according to the cellularity of adipose tissue has given associations with clinical observations such as age at debut of obesity, disturbances of carbohydrate and lipid metabolism, and with prognosis for treatment. These relationships seem to justify the adipose cellularity measurements as they are now performed, although only a fairly rough estimate of the total cell number is obtained.