Femoral Adipose Tissue Research Articles

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.

Serum leptin levels and leptin expression in growth hormone (GH)-deficient and healthy adults: Influence of GH treatment, gender, and fasting

Growth hormone (GH) treatment is associated with a reduction in fat mass in healthy and GH-deficient (GHD) subjects. This is mainly mediated via a direct GH action on adipose cells and stimulation of lipolysis. Leptin is secreted from adipose tissue and may be involved in signaling information about adipose tissue stores to the brain. Hormonal regulation of leptin is still not fully elucidated, and in the present study, we investigated both the long-term (4-month) and short-term (28-hour) GH effects on serum leptin and leptin gene expression in subcutaneous adipose tissue. In GHD adults (n = 24), leptin correlated with most estimates of adiposity ( r = .62 to .86), as previously found in healthy subjects. However, no correlation was observed with intraabdominal fat determined by computed tomographic (CT) scan (INTRA-CT). GH treatment for 4 months had no independent effect on either serum leptin or leptin gene expression. In a short-term study, we found that fasting gradually reduced leptin levels in both healthy men and GHD adults, with a maximum reduction of 58% to 60% ( P < .01) after 31 hours. No independent effect of GH suppression or GH substitution on serum leptin was found during fasting. Adipose tissue leptin mRNA correlated with serum leptin ( r = .51, P < .01) and the body mass index ([BMI] r = .55, P < .05). Serum leptin levels and gene expression were significantly higher in women compared with men (26.6 ± 5.8 v 10.0 ± 1.30 ng/mL, P < .05). However, in regression analysis accounting for the gender differences in subcutaneous femoral adipose tissue (FEM-CT), the difference in serum leptin disappeared, indicating that subcutaneous femoral fat or factors closely related to femoral fat (eg, sex hormones) may be causal factors for the gender difference in leptin.

The effect of a physiological growth hormone pulse on lipolysis in abdominal and femoral adipose tissue assessed by microdialysis

The effect of a physiological growth hormone pulse on lipolysis in abdominal and femoral adipose tissue assessed by microdialysis

Adenoviral-mediated gene transfer to human adipocytes in vitro, and human adipose tissue ex vivo and rabbit femoral adipose tissue in vivo.

Adenoviral-mediated gene transfer has proven useful in several organ systems to understand gene action and to provide a potential therapeutic modality for localized, organ-specific gene overexpression. However, the application of adenoviral-mediated gene transfer to adipocytes and adipose tissue has not been evaluated. We evaluated the feasibility of in vitro and ex vivo transfer of the beta-galactosidase gene to human adipocytes and adipose tissue by means of adenoviral vectors. The efficiency (percentage of cells transduced) of adenoviral-mediated gene transfer of the beta-galactosidase gene to human adipocytes in vitro and to human adipose tissue ex vivo was 21 +/- 3% and 14 +/- 3%, respectively. Adenoviral-mediated gene transfer in a rabbit femoral adipose tissue was also demonstrated in vivo. Adenoviral-mediated gene transfer may facilitate studies on understanding the biology of adipocytes and provide a potential tool for the modulation of adipocyte function in vivo and thereby for the treatment of obesity.

Evidence for sex steroid inhibition of lipoprotein lipase in men: Comparison of abdominal and femoral adipose tissue

Plasma estradiol has been suggested to suppress adipose tissue lipoprotein lipase (LPL) activity in women. The present study explores the regulation of LPL by sex steroids in sedentary obese men (N = 24) at their usual weight. Femoral adipose tissue LPL activity, eluted with serum and heparin or extracted with detergent, showed significant inverse correlations with plasma levels of testosterone, bioavailable testosterone, dihydrotestosterone, and estradiol. Both measures of femoral LPL activity were also correlated with the weight change occurring despite efforts to maintain a constant weight. Abdominal LPL activity showed significant but weaker inverse correlations with bioavailable testosterone only. Multivariate analysis of potential predictors for eluted femoral LPL activity showed that plasma testosterone, dihydrotestosterone, and estradiol were interdependent, whereas the rate of weight change was an independent variable. In the regression equation, only bioavailable testosterone and weight change were retained, explaining 63% of the variability ( R = .79, P = .0002). These results suggest that sex steroids suppress adipose tissue LPL activity in men, and more so in the thigh than in the abdomen, thereby possibly contributing to a central fat accumulation. The data are compatible with a model from male animals suggesting that testosterone effects on adipose tissue LPL are mediated by estradiol formed locally.

Fat distribution and cardiovascular risk factors in obese adolescent girls: importance of the intraabdominal fat depot

The regional distribution of body fat has repeatedly been found to be a significant and independent risk factor for cardiovascular disease in both obese men and women. To determine whether abnormalities in the lipid-lipoprotein profile and systolic and diastolic blood pressure are related to specific fat depots early in the course of obesity, we used magnetic resonance imaging to measure accurately intraabdominal and subcutaneous fat masses in 14 obese [body mass index (BMI; in kg/m2) 30 +/- 1.3] and 10 nonobese (BMI: 21 +/- 0.5) adolescent girls matched for age and Tanner stage of development. Intraabdominal and subcutaneous fat depots were two- to threefold greater in obese than in nonobese girls (P < 0.01). Total cholesterol, triacylglycerol, low-density-lipoprotein (LDL) cholesterol, basal insulin, and systolic and diastolic blood pressure were significantly higher in obese adolescent girls than in control subjects. In obese girls, intraabdominal fat but not BMI or waist-to-hip ratio was highly correlated with basal insulin (r = 0.55, P < 0.04), triacylglycerols (r = 0.53, P < 0.03), and high-density-lipoprotein (HDL) cholesterol (r = -0.54, P < 0.04). Femoral adipose tissue was inversely related to triacylglycerol (r = -0.51) and LDL cholesterol (r = -0.56, P < 0.05) concentrations in obese girls. The study indicates that early in the natural history of obese adolescent girls, cardiovascular risk factors are related to the amount of intraabdominal fat.

Does lipoprotein or hepatic lipase activity explain the protective lipoprotein profile of premenopausal women?

Numerous studies have reported that women have a lipoprotein profile suggestive of a reduced risk of coronary heart disease (CHD). We have therefore tested whether the “protective” lipoprotein profile of women could be explained by differences in hepatic lipase (HL) or lipoprotein lipase (LPL) activities. In the present study, 14 non-obese healthy premenopausal women had higher plasma concentrations of high-density lipoprotein cholesterol (HDL-C), HDL 2-C, HDL 3-C, and HDL—apolipoprotein (apo) Al, and a higher ratio of HDL-C to low-density lipoprotein cholesterol (LDL-C) than 17 non-obese healthy men. Women also had lower plasma triglyceride (TG), HDL-TG, and apo B levels than men. Plasma postheparin LPL (PH-LPL) and HL activities showed no significant sex dimorphism, whereas abdominal and femoral adipose tissue (AT)-LPL activities were significantly higher in women ( P < .005). In men, PH-LPL activity correlated significantly with plasma HDL 2-C ( r = .52, P < .05), LDL-C ( r = −.47, P < .05), and apo B ( r = −.56, P < .01) levels, as well as with the HDL-C LDL-C ratio ( r = .67, P < .005). No such relationships were found in women, with the exception of HL activity, which was negatively correlated with HDL—apo Al levels. In both genders, abdominal AT-LPL activity showed no significant association with plasma lipoprotein levels. In contrast, femoral AT-LPL activity in women was positively correlated with plasma HDL-C, HDL 2-C ( r = .53, P < .05 and r = .69, P < .01, respectively), and HDL—apo Al ( r = .52, P < .01) levels, as well as with the HDL-C LDL-C ratio ( r = .62, P < .01). These associations were not found in men. Analysis of covariance (ANCOVA) showed that adjustment for HL activity could not explain sex differences in lipoprotein levels. When correction for PH-LPL activity was performed, gender differences observed in plasma lipoprotein levels remained significant. In ANCOVA with inclusion of abdominal AT-LPL activity as a covariate, men still had plasma TG levels significantly higher than women, whereas HDL-C, HDL 2-C, HDL—apo Al, and HDL 3-C concentrations were lower. Finally, femoral AT-LPL activity was the most powerful covariate explaining gender differences in plasma lipoprotein levels. Indeed, adjustment for femoral AT-LPL activity eliminated gender differences in plasma TG, HDL-C, HDL 2-C, HDL—apo Al, and apo B levels and the HDL-C LDL-C ratio , with the exception being the HDL 3-C level. Although these results do not provide evidence for a cause-and-effect relationship, they suggest that the high femoral AT-LPL activity is a significant correlate of the favorable plasma lipoprotein-lipid profile in women.

Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens

Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens

Comparison of two methods to assess the tissue/blood partition coefficient for xenon in subcutaneous adipose tissue in man

A new method to calculate the tissue/blood partition coefficient (lambda) for xenon in studies on the subcutaneous adipose tissue blood flow was compared with a previously reported method based on local skinfold thickness (lambda LST). The former method included needle biopsies from the abdominal and femoral subcutaneous adipose tissue, and the mean fat cell diameter was measured (lambda ECT). The extracellular tissue fraction in subcutaneous tissue was then estimated from a diagram. The tissue lipid content was approximated to equal the relative intracellular volume and Ostwald's solubility coefficients for 133Xe, based on the distribution of xenon in lipid, albumin and 0.9% saline were applied. Estimated lambda-values based on needle biopsies from the abdominal site were: 8.6 +/- 0.1 versus 9.9 +/- 0.4 ml g-1 (mean +/- SE) (P < 0.05) and from the femoral site: 9.1 +/- 0.1 versus 9.6 +/- 0.2 in lean (n = 10) and obese subjects (n = 10), respectively. The corresponding lambda-values obtained from skinfold measurements were: 6.2 +/- 0.5 versus 11.0 +/- 0.4 (P < 0.001) and 6.9 +/- 0.3 versus 11.4 +/- 0.4 (P < 0.001) in lean and obese subjects, respectively. Pooled lambda LST-values correlated positively with estimated adipose tissue blood flow (ATBF) (r: 0.34, P < 0.05, n = 40) whereas no such correlation was found for lambda ECT-values. In conclusion, a new method is presented which may allow an accurate determination of, and which may lead to reliable data on, subcutaneous ATBF in both lean and obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactate release from the subcutaneous tissue in lean and obese men.

Lactate concentration in the subcutaneous interstitial fluid and adipose tissue blood flow (ATBF, ml/100 g.min) were simultaneously measured with the microdialysis technique combined with 133Xe clearance in the abdominal and femoral subcutaneous adipose tissue in nine lean and nine obese men. The studies were performed both in the postabsorptive state and 2 h after an oral glucose load and the results compared to the lactate levels in arterialized venous plasma. After an overnight's fast, arterial lactate was 738 +/- 49 and 894 +/- 69 microM (mean +/- SE) (P < 0.05) in the lean and obese subjects, respectively. The interstitial lactate levels were significantly higher than blood lactate in both subject groups without any regional differences. Abdominal and femoral ATBF was 3.2 +/- 0.6 vs. 2.8 +/- 0.4 and 1.7 +/- 0.3 vs. 2.4 +/- 0.4 ml/100 g.min (P < 0.05) in lean and obese subjects, respectively. Mean apparent lactate release from the abdominal vs. femoral adipose tissue in the fasting state was 10.5 +/- 3.1 vs. 8.6 +/- 2.3 and 6.0 +/- 2.3 vs. 8.5 +/- 2.3 mumol/kg.min (NS) in lean and obese subjects, respectively. Both plasma and interstitial lactate levels increased significantly after an oral glucose load in both subject groups. However, apparent lactate release increased significantly only in the lean group. It is concluded that subcutaneous adipose tissue is a significant source of whole-body lactate release in the postabsorptive state and that this is further enhanced in obese subjects due to their large adipose mass.

Abdominal and femoral adipose tissue lipolysis and cardiovascular disease risk factors in men

The relationships between subcutaneous abdominal and femoral fat cell lipolyses, plasma free-fatty acid (FFA) levels and metabolic variables considered as risk factors for cardiovascular disease (CVD) (plasma glucose, insulin and lipoprotein levels) were investigated in 54 men, aged 36 +/- 3 (SD) years, covering a wide range of body fatness values (body mass indices from 19 to 34 kg m-2). Although there were no consistent relationships between femoral fat cell weight and the metabolic profile, positive and significant associations were found between abdominal fat cell weight and most of the metabolic indices. However, abdominal fat cell lipolysis measured with an alpha 2-(clonidine) or a beta-agonist (isoproterenol) was unrelated to metabolic variables. In contrast, femoral fat cell lipolysis measured in the presence of clonidine was positively associated with fasting plasma insulin, cholesterol (CHOL) and apolipoprotein (apo) B levels, as well as with LDL-CHOL and LDL-apo B concentrations. No association was found between isoproterenol-stimulated lipolysis of femoral adipocytes and the metabolic profile. Comparison of two subgroups of men with either low or high femoral residual lipolysis with clonidine revealed that subjects with the lowest femoral alpha 2-adrenergic component (i.e. the highest residual lipolysis) displayed significant alterations in both plasma lipid-lipoprotein and glucose-insulin levels which could be predictive of an increased risk of CVD. Free fatty acid (FFA) levels measured in the fasting state and during an oral glucose tolerance test (OGTT) were positively associated with fasting plasma insulin and triglyceride levels as well as with both glucose and insulin areas measured during the OGTT. However, regional adipose tissue lipolysis measured in vitro was unrelated to plasma FFA levels. These results support the view that both femoral adipose tissue lipolysis and plasma FFA levels are significant correlates of plasma glucose-insulin homeostasis and lipoprotein-lipid levels, in men. However, as adipose tissue lipolysis and plasma FFA are unrelated to each other, they may be associated with risk variables through independent mechanisms.

Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men.

To further understand the factors involved in the regulation of high plasma triglyceride (TG) or low plasma high density lipoprotein cholesterol (HDL-C) levels, three groups of male subjects (normal TG with low HDL-C levels, high TG with normal HDL-C levels, and high TG with low HDL-C levels) were compared with a sample of normolipemic men with normal TG and HDL-C plasma levels. Mean age was 34 years (range, 20-42 years), and none of the subjects had plasma TG levels > 4.0 mmol/l or familial hypercholesterolemia. Both groups of subjects with high TG levels had a higher body mass index, waist circumference, waist-to-hip circumferences ratio, and a higher ratio of abdominal to femoral adipose tissue areas as measured by computed tomography when compared with normolipemic control subjects. However, during an oral glucose tolerance test only high TG-low HDL-C men had fasting hyperinsulinemia and higher plasma insulin levels compared with normolipemic subjects. In addition, the high TG-low HDL-C group showed reduced HDL apoprotein (apo) A-I levels and a low HDL2-C/HDL3-C ratio. These changes were observed along with a nonsignificant trend for a lower plasma postheparin lipoprotein lipase activity. However, among subjects with high TG and normal HDL-C levels, no evidence of insulin resistance or of a reduction in postheparin lipoprotein lipase activity was observed, suggesting that the high plasma TG levels could be attributed to an increased production of apo B-containing lipoproteins, as high plasma apo B and low density lipoprotein (LDL)-apo B levels were observed in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of glucose carbon in muscle glycogen and adipose tissue triglycerides in vivo in humans.

Glucose disposal into muscle glycogen has previously been directly studied after intravenous, but not after physiological, oral administration. In this study 100 g glucose, containing 50 microCi [U-14C]glucose, were taken orally by premenopausal women in the overnight fasting state or after a carbohydrate-rich meal. After 4 h, biopsies were taken from the vastus lateralis muscle and abdominal and femoral subcutaneous adipose tissue for determinations of label in isolated glycogen and triglycerides, respectively. Uptake of administered glucose carbon in muscle glycogen was estimated to be approximately 20 g in the fasting and approximately 9 g in the carbohydrate-fed groups, respectively. Total uptake in adipose tissue triglycerides was approximately 2 g. Glucose carbon uptake in muscle glycogen correlated positively with glucose infusion rates during euglycemic hyperinsulinemic glucose clamps, glycogen synthase activity in vitro, and type I muscle fiber distribution and fiber area. Negative correlations were found between glucose uptake in adipose tissue triglycerides, type II fiber distribution and fiber area, as well as the waist-to-hip circumference ratio and degree of obesity. It was concluded that muscle glycogen is probably not a major pathway for disposal of oral glucose carbon in the sedentary condition.

Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels

The associations of adipose tissue lipoprotien lipase (AT-LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT-LPL activity. In this regard, heparin-releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre-menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT-LPL activities expressed per 10(6) cells. However, abdominal and femoral AT-LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT-LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT-LPL activity tended to be negatively correlated with plasma HDL-cholesterol levels, femoral AT-LPL activity was positively correlated with plasma HDL2-cholesterol (r = 0.40, P less than 0.05) concentration and with the HDL2-cholesterol/HDL3-cholesterol ratio (r = 0.49, P less than 0.01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT-LPL activity and plasma HDL2-cholesterol levels lead us to suggest that AT-LPL activity may not be causally related with plasma HDL levels.

Regional Adipose Tissue Metabolism in Postmenopausal Women After Treatment with Exogenous Sex Steroids

In order to evaluate the effect of exogenous sex steroids on adipose tissue metabolism, two groups of postmenopausal women were studied. In one of the groups, the effect of 50 micrograms ethinyl estradiol (EE) was investigated given orally alone and in combination with 10 mg norethisterone acetate (NET). This combination is reminiscent of an old high dose oral contraceptive. In the other group, the effect of 3 mg 17 beta-estradiol was evaluated when administered percutaneously alone and in combination with 300 mg micronized progesterone given orally. These substances and doses were chosen to provide a "physiological" hormonal influence. In the femoral region 50 micrograms EE induced an increase in LPL activity. This elevated LPL value was reversed with the addition of 10 mg NET. Moreover, during treatment with 50 micrograms EE, a decrease in norepinephrine stimulated lipolysis was seen in the abdominal region. The percutaneous administration of 17 beta-estradiol with or without micronized progesterone, however, was inert as regards subcutaneous adipose tissue metabolism. Our findings indicate, therefore, that EE in doses used in oral contraception might promote lipid accumulation in the femoral adipose tissue depot.

Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women.

Intra-abdominal fat content is an important variable in the association between regional body fat distribution and plasma high density lipoprotein (HDL) cholesterol levels. In the present study, we report on the role of plasma postheparin lipases as well as abdominal and femoral adipose tissue lipoprotein lipase activities in the association between body fat distribution and plasma lipoprotein levels. Postheparin plasma lipoprotein lipase (LPL), hepatic-triglyceride lipase (H-TGL), abdominal and femoral adipose tissue (AT)-LPL activities and plasma lipoprotein levels were measured after an overnight fast in a sample of 16 obese women (ages 36.0 +/- 6.1 years [mean +/- SD], percent body fat 46% +/- 6%). Computed axial tomography was used to assess body fat distribution. Plasma postheparin LPL activity was neither correlated with total adiposity nor with the level of intra-abdominal fat. Intra-abdominal fat deposition was, however, positively correlated with H-TGL activity (r = 0.66, p less than 0.005). Furthermore, covariance analysis showed that the association between intra-abdominal fat and H-TGL was independent from total adiposity. Plasma postheparin LPL and abdominal AT-LPL activities showed no significant correlation with plasma lipoprotein levels, whereas femoral AT-LPL activity was positively correlated with the HDL2 cholesterol/HDL3 cholesterol ratio (r = 0.51, p less than 0.05). H-TGL activity was, however, negatively correlated with HDL2 cholesterol (r = -0.60, p less than 0.05), but not with HDL3 cholesterol (r = -0.28, NS). These results suggest that the high H-TGL activity in obese women with excess deep abdominal fat could be responsible for the reduction in plasma HDL2 cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometric Variables and Metabolism in Polycystic Ovarian Disease

Anthropometric, endocrine and metabolic variables, were examined in women with polycystic ovarian syndrome (PCO), and in normal control women. Obese women with PCO had higher plasma insulin values than non obese women with PCO, but lean body mass, glucose tolerance, plasma triglycerides and blood pressure were not different in spite of almost twice the body fat mass in the obese PCO women. However, in comparisons between non-obese PCO and control women, with equal body fat mass, the PCO women had higher blood pressure, plasma triglycerides and insulin, as well as a tendency to increased lean body mass. Both PCO groups had a high waist/hip ratio and larger abdominal fat cells than controls, indicating a preferential abdominal accumulation of adipose tissue. In comparison with abdominal adipocytes, femoral adipocytes were larger and had higher lipoprotein lipase activity in the control women, while in the PCO women these regional differences were not found. Basal and norepinephrine stimulated lipolysis were higher in the abdominal than femoral adipocytes in all groups. Substitution of the PCO women with ethinyl estradiol plus desogestrel during 6 months resulted in a regression of clinical androgenic symptoms as well as a normalization of plasma concentrations of free testosterone and sex hormone binding globulin. However, neither body composition nor metabolism were normalized. It was concluded that body fat distribution is more closely related to hypertension and metabolic derangements than total fat mass in the PCO syndrome. It is suggested that the relative paucity of femoral adipose tissue is due to a lack of specific effects of progesterone on adipocytes in this region.

Effect of fasting on insulin receptor binding and insulin action in different human subcutaneous fat depots.

The possible existence of regional variations in fasting-mediated changes on insulin action an human adipose tissue was investigated in vitro. Subcutaneous adipose tissue was obtained from the femoral, abdominal, and gluteal areas of obese but otherwise normal subjects (16 women and 7 men) before and after 7 days of total fasting. Specific insulin receptor binding to isolated fat cells was similar in femoral and abdominal adipose tissues before and after fasting. However, the latter condition was associated with a significant increase in insulin receptor binding at low hormone concentrations (less than 2 nmol/liter) in gluteal adipocytes. Insulin stimulated glucose oxidation in a dose-dependent way in all 3 adipose regions before fasting. In the femoral and gluteal sites after fasting, the maximum insulin effect was significantly decreased, but a dose-dependent insulin effect was still present, and there was no change in insulin sensitivity. However, abdominal adipose tissue after fasting was completely unresponsive to insulin stimulation when the hormone was added in increasing concentrations up to 80 nmol/liter. The results in fasting women were similar to those in the whole study group. In conclusion, there appear to be marked regional variations in fasting-mediated changes in insulin action on glucose metabolism in human adipose tissue. Alterations at the postreceptor level which lead to insulin resistance appear to be of greater importance than the counteracting receptor changes.