Visceral Adipose Tissue and Markers of the Insulin Resistance Syndrome in Obese Black and White Teenagers

Objective: To determine the relationships between visceral and general adiposity, cardiovascular fitness, and markers of the insulin resistance syndrome in obese black and white teenagers. Research Methods and Procedures: Cross‐sectional survey of 81 obese 13‐ to 16‐year‐old youths. Visceral adipose tissue was measured with magnetic resonance imaging, and percentage body fat was measured with dual‐energy X‐ray absorptiometry. Cardiovascular fitness was assessed with a submaximal treadmill test. Fasting blood samples were analyzed for lipids/lipoproteins and insulin. Resting blood pressure was obtained using an automated cuff. Results: Visceral adipose tissue was significantly correlated with unfavorable levels of: triacylglycerol (r = 0.27, p < 0.05), total cholesterol (r = 0.27, p < 0.05), high‐density lipoprotein cholesterol (r = ?0.26, p < 0.05), the ratio of total cholesterol/high‐density lipoprotein cholesterol (r = 0.42, p < 0.01), low‐density lipoprotein cholesterol (r = 0.27, p < 0.05), apolipoprotein B (r = 0.38, p < 0.01), and systolic blood pressure (r = 0.30, p < 0.01). Multiple regression analyses revealed that visceral adipose tissue was more powerful than percentage body fat for explaining variance in lipoproteins (e.g., for the ratio of total cholesterol/high‐density lipoprotein cholesterol, r² = 0.13, p < 0.01, and for systolic blood pressure, r² = 0.07, p < 0.05). Ethnicity was the most powerful of the demographic predictors for blood lipids (r² = 0.15 for triacylglycerol with lower levels in blacks; r² = 0.10 for high‐density lipoprotein cholesterol with higher levels in blacks; r² = 0.06 for the ratio of total cholesterol/high‐density lipoprotein cholesterol with lower levels in blacks). Cardiovascular fitness was not retained as a significant predictor of markers of the insulin resistance syndrome. Discussion: Some of the deleterious relationships between visceral adiposity and markers for the insulin resistance syndrome seen in adults were already present in these obese young people.     

Effects of Weight Reduction on Serum Vaspin Concentrations in Obese Subjects: Modification by Insulin Resistance

Visceral adipose tissue‐derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12‐week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMA_IR). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMA_IR group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMA_IR group was positively correlated with change in BMI and negatively correlated with initial HOMA_IR level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMA_IR group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables.     

Modest Lifestyle Intervention and Glucose Tolerance in Obese African Americans

Objective: Previous studies have demonstrated the benefit of short‐term diets on glucose tolerance in obese individuals. The purpose of this study was to evaluate the effectiveness of modest lifestyle changes in maintaining improvements in glucose tolerance induced by short‐term energy restriction in obese African Americans with impaired glucose tolerance or type 2 diabetes mellitus. Research Methods and Procedures: An intervention group (n = 45; 47 ± 1 year [mean ± SE]), 105 ± 4 kg; body mass index: 39 ± 1 kg/m²) received an energy‐restricted diet (943 ± 26 kcal/d) for 1 week, followed by a lifestyle program of reduced dietary fat (?125 kcal/d) and increased physical activity (+125 kcal/d) for 1 year. Body weight and plasma concentrations of glucose, insulin, and C‐peptide during an oral glucose tolerance test were measured at baseline, 1‐week, and 4‐month intervals. A control group (n = 24; 48 ± 1 year; 110 ± 5 kg; body mass index: 41 ± 2 kg/m²) underwent these measurements at 4‐month intervals. Results: No changes in weight or glucose tolerance were observed in the control group. The intervention group had significant (p < 0.05) improvements in body weight and glucose tolerance in response to the 1‐week diet, which persisted for 4 months (p < 0.001 vs. control for change in weight). A total of 19 subjects (42%) continued the intervention program for 1 year, with sustained improvements (weight: ?4.6 ± 1.0 kg; p < 0.001 vs. control; oral glucose tolerance test glucose area: ?103 ± 44 mM · min; p < 0.05 vs. control). Discussion: A modest lifestyle program facilitates weight loss and enables improvements in glucose tolerance to be maintained in obese individuals with abnormal glucose tolerance. However, attrition was high, despite the mild nature of the program.     

Circulating Interleukin‐6 in Relation to Adiposity,Insulin Action,and Insulin Secretion

Objective: Plasma concentrations of interleukin‐6 (IL‐6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL‐6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. Research Methods and Procedures: Fasting plasma IL‐6 concentrations (enzyme‐linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). Results: Fasting plasma IL‐6 concentrations were positively correlated with percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r = ?0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p = 0.339). After adjusting for percentage of body fat, plasma IL‐6 was not related to M (partial r = ?0.23, p = 0.089). Discussion: Fasting plasma IL‐6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL‐6 and insulin action seems to be mediated through adiposity.     

肥胖诱发胰岛素抵抗的炎性机制

肥胖可诱发一系列慢性代谢性疾病,如2型糖尿病、血脂障碍、高血压和非酒精性脂肪肝等.这些疾病构成了当今世界人类健康的极大威胁.胰岛素抵抗是这些疾病的共有特征.胰岛素抵抗的发生与慢性低度系统炎性密切相关,涉及多条炎性信号通路的激活和胰岛素信号转导的缺陷.本文综述了肥胖、炎性与胰岛素抵抗之间的本质联系,以及肥胖诱发胰岛素抵抗的炎性机制,以期为肥胖相关疾病的防治提供重要参考.     

New scanning electron microscopic method for determination of adipocyte size in humans and mice

Objective: To evaluate a new scanning electronic microscopic (EM) method for assessing fat cell sizes and compare fat cell size distribution in human adipose tissue from different fat depots before and after weight loss. Research Methods and Procedures: Identical human fat tissue biopsies were separated into two fractions: one used to prepare a fat cell suspension by collagenase digestion followed by photomicrography (collagenase method) and the other fixed in formalin for EM analysis. The EM method was evaluated further by determining fat cell sizes from lean and ob/ob mice. Finally, the EM method was used to assess fat cell sizes in biopsies of different human depots from before and after weight loss. Results: Fat cell size distributions measured by the two methods were not identical, but differences were generally small. The EM method reproduced the well‐documented fat cell size difference between lean and ob/ob mice. Large variation was detected in fat cell distributions among three depots in humans. Weight loss reduced fat cell sizes in subjects with large baseline fat cells but had no effect in subjects with small baseline fat cell sizes. Discussion: Our results suggest that the EM method may be a useful alternative for fat cell size analysis of clinical samples.     

Alteration of Amine Oxidase Activity in the Adipose Tissue of Obese Subjects

Objective: To explore the activity of monoamine oxidases (MAOs) and semicarbazide‐sensitive amine oxidases (SSAOs) in adipose tissue and blood of lean and moderately obese subjects and to study whether there is a link between these hydrogen peroxide‐generating enzymes and blood markers of oxidative stress. Research Methods and Procedures: Nine obese male subjects (BMI 32.6 ± 0.4 kg/m²) and nine controls (BMI 23.4 ± 0.5) of 24‐ to 40‐year‐old subjects were included in the study. MAO and SSAO activities were measured on microbiopsies of abdominal subcutaneous adipose tissue by quantifying ¹⁴C‐tyramine and ¹⁴C‐benzylamine oxidation. Levels of soluble SSAO, lipid peroxidation products, and antioxidant agents were measured in plasma, whereas cytoprotective enzymes were determined in blood lysates. Results: The high MAO activity found in adipose tissue was diminished by one‐half in obese subjects (maximum initial velocity of 1.2 vs. 2.3 nmol tyramine oxidized/mg protein/min). There was no change in SSAO activity, either under its adipose tissue‐bound or plasma‐soluble form. Plasma levels of lipid peroxidation products and antioxidant vitamins remained unmodified, as well as erythrocyte antioxidant enzymes, whereas circulating triglycerides, insulin, and leptin were increased. Discussion: Although they already exhibited several signs of endocrino‐metabolic disorders, the obese men did not exhibit the increase in blood markers of oxidative stress or the decrease in antioxidant defenses reported to occur in very obese or diabetic subjects. The reduced MAO and the unchanged SSAO activities found in obesity suggest that these hydrogen peroxide‐generating enzymes expressed in adipocytes are probably not involved in the onset of the oxidative stress found in severe obesity and/or in its complications.     

Hepatic Insulin Resistance in Obese Non-Diabetic Subjects and in Type 2 Diabetic Patients

Objective: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. Research Methods and Procedures: To estimate their hepatic insulin sensitivity, we measured the rate of exogenous insulin infusion required to maintain mildly elevated glycemia in obese patients with type 2 diabetes, obese non-diabetic patients, and lean control subjects during constant infusions of somatostatin and physiological low-glucagon replacement infusions. To account for differences in insulin concentrations among the three groups of subjects, an additional protocol was also performed in healthy lean subjects with higher insulin infusion rates and exogenous dextrose infusion. Results: The insulin infusion rate required to maintain glycemia at 8.5 mM was increased 4-fold in obese patients with type 2 diabetes and 1.5-fold in obese non-diabetic patients. The net endogenous glucose production (measured with 6,6-²H₂-glucose) and total glucose output (measured with 2-²H₁-glucose) were ∼30% lower in the patients than in the lean subjects. Net endogenous glucose production and total glucose output were both markedly increased in both groups of obese patients compared with lean control subjects during hyperinsulinemia. Discussion: Our data indicate that both obese non-diabetic and obese type 2 diabetic patients have a blunted suppressive action of insulin on glucose production, indicating hepatic and renal insulin resistance.     

Contribution of Adipokine Gene Expression in Mesenteric Adipose Tissue to the Pathogenesis of Insulin Resistance in Obese Patients

Mesenteric adipose tissue, being a component of visceral adipose tissue, has a high lipolytic activity. Excessive accumulation of visceral adipose tissue increases the risk of metabolic disorders leading to severe consequences. Therefore, the aim of the presented study was to estimate the production of adipokine and proinflammatory molecules by the adipose tissue of small intestine mesentery evaluating its contribution to the formation of insulin resistance in obesity. The role of the activity of LEP, SERPINA12, RARRES2, and TNFα genes encoding leptin, vaspin, chemerin, and TNFα in adipose tissue of small intestinal mesentery in patients with abdominal obesity with a different state of carbohydrate metabolism was studied. The changes in serum/plasma content of the examined mediators that we detected are closely associated with their production in the adipose tissue of small intestinal mesentery. The revealed interrelations between the production of mediators (adipokines, proinflammatory molecules) studied with the parameters of carbohydrate metabolism indicate an important role of mesenteric adipose tissue in the formation of insulin resistance in obesity.     

Reduced Expression of FOXC2 and Brown Adipogenic Genes in Human Subjects with Insulin Resistance

Objective: We investigated subcutaneous adipose tissue expression of FOXC2 and selected genes involved in brown adipogenesis in adult human subjects in whom we have previously identified a reduced potential of precursor cell commitment to adipose‐lineage differentiation in relation to insulin resistance. Research Methods and Procedure: Gene expression was studied using quantitative real time polymerase chain reaction. The relation between the expression of brown adipogenic genes and the genes involved in progenitor cell commitment, adipose cell size, and insulin sensitivity in vivo was analyzed. Results: The expression of FOXC2, MASK, MAP3K5, retinoblastoma protein (pRb), peroxisome proliferator‐activated protein gamma (PPARγ), and retinoid X receptor gamma (RXRγ) was decreased in the insulin‐resistant compared with insulin‐sensitive subjects, whereas PPARγ‐2 and CCAAT/enhancer binding protein alpha (C/EBPα) showed no differential expression. The FOXC2 expression correlated with that of Notch and Wnt signaling genes, as well as of the genes studied participating in brown adipogenesis, including MASK, MAP3K5, PPARγ, pRb, RXRγ, and PGC‐1. A second‐level correlation between PPARγ and UCP‐1 was also significant. In addition, the expression of MASK, MAP3K5, pRb, RXRγ, and PGC‐1 inversely correlated with adipose cell mass and also correlated with the glucose disposal rate in vivo. Discussion: Our results suggest that a reduced brown adipose phenotype is associated with insulin resistance and that a basal brown adipose phenotype may be important for maintaining normal insulin sensitivity.     

Plasma Cortisol Levels Increase with Age in Obese Subjects

In order to assess the influence of age, sex, and body mass on plasma cortisol concentrations, we measured the 24-hour Integrated Concentration (IC) of cortisol (F) in 36 obese subjects (16 males, 20 females) aged 5.3–56.4 years, BMI=35.5 ± 7.3 kg/m² and compared with 119 nonobese subjects, body mass indices (BMI) 21.2 ± 2.7 kg/m², aged 8.8–66.2 years (55 males, 64 females). Subjects were nondiabetic, normotensive, without history of psychiatric illness, and otherwise in good health. IC studies were performed using a continuous blood withdrawal methodology, and IC-F was assayed from the 24 hour pooled sample by a protein binding method. The effect of age and gender on IC-F was analyzed by multivariate regression. In the nonobese group there was no effect of age or sex on IC-cortisol levels, the mean IC-F= 173.8 ± 44.1 nmol/L. A statistically significant but weak negative effect of BMI on IC-cortisol (r = -.18, p<0.05) was present. In the obese subjects there was a significant increase in IC-cortisol levels with age IC-F(nmol/L)=2.76 x age(years) + 85.0 (r²=.36, p<0.0001). IC-cortisol levels tended to be lower in obese males than females when controlled for age (p<0.05). We conclude that in nonobese subjects IC-F levels are independent of age and gender. However, there is a significant increase of IC-cortisol levels with age in obese individuals. The observed increase of IC-cortisol with age may contribute to metabolic complications of obesity.     

Body Compartment and Subcutaneous Adipose Tissue Distribution - Risk Factor Patterns in Obese Subjects

The purpose of this study was to investigate whether upper body obesity and/or visceral obesity are related to cardiovascular risk factors among severely obese subjects, phenomena that have previously been reported in more heterogeneous body weight distri -buttons. 2450 severely obese men and women aged 37 to 59 years, with a body mass index of 39 ± 4.5 kg/m² (mean ± SD) were examined cross-sectionally. Eight cardiovascular risk factors were studied in relation. to the following body composition indicators: four trunk and three limb circumferences, along with weight, height and sagittal trunk diameter. From the latter three measurements lean body mass (LBM, i.e., the non-adipose tissue mass) and the masses of subcutaneous and visceral adipose tissue were estimated by using sex-specific prediction equations previously calibrated by computed tomography. Two risk factor patterns could be distinguished: 1. One body compartment- risk factor pattern in which the subcutaneous adipose tissue (AT) mass and, in particular, the visceral AT mass were positively related to most risk factors while the lean body mass was negatively related to some risk factors. 2. One subcutaneous adipose tissue distribution- risk factor pattern in which the neck circumference was positively and the thigh circumference negatively related to several risk factors. It is concluded that lean body mass (LBM), visceral and subcutaneous adipose tissue masses as well as neck and thigh circumferences, used as indices of subcutaneous adipose tissue distribution, are independently related to cardiovascular risk factors in severely obese men and women.     

不同强度电针对肥胖大鼠脂肪组织炎症相关因子的影响

探讨不同强度电针对肥胖大鼠脂肪组织核因子-κBp65(NF-κBp65)、单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)的作用差异.将SD大鼠随机分为普通饮食组、高脂饮食组、5 V电针组、2.5 V电针组,除普通饮食组外其余各组大鼠均饲以高脂饲料.取"足三里"、"三阴交"穴,不同强度电针治疗14 d后,用蛋白质印迹技术(Western blot)检测肥胖大鼠附睾脂肪组织NF-κBp65的表达,酶联免疫吸附法(ELISA)检测肥胖大鼠附睾脂肪组织MCP-1、TNF-α的含量.研究发现两电针组肥胖大鼠体重、Lee’s指数、脂肪组织中NF-κBp65表达、MCP-1和TNF-α含量较高脂饮食组显著降低(P<0.01),5 V电针组较2.5 V电针组下降效果更为明显(P<0.01,P<0.05).结果表明电针可改善肥胖脂肪组织炎症反应状态,减轻肥胖大鼠体重,且5 V电针组效果优于2.5 V电针组.     

Effect of Orlistat in Obese Patients with Binge Eating Disorder

Objective: Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder. Research Methods and Procedures: Eighty‐nine patients with clinically diagnosed binge eating disorder and a BMI ≥ 30 kg/m² were randomized in double‐blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced‐calorie diet. Results: After 24 weeks, the mean weight loss from baseline for orlistat‐treated patients was significantly greater than for patients receiving placebo (?7.4% vs. ?2.3%; p = 0.0001) (intent‐to‐treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011) Discussion: Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.     

Influence of Magnesium on Insulin Resistance in Obese Women

The present study evaluated the influence of magnesium on insulin resistance in obese women. A case-control study involving 114 women on the age between 20 and 50 years old, divided into two groups: control (eutrophic women, n?=?59) and case (obese women, n?=?55). The analysis of magnesium intake was carried out through the 3-day food record and also NutWin software version 1.5. The plasma, erythrocyte, and urinary magnesium concentrations were determined by flame atomic absorption spectrophotometry. The determinations of serum glucose and serum insulin were performed by enzymatic colorimetric method and chemiluminescence, respectively. The insulin resistance was assessed by homeostasis model assessment insulin resistance (HOMA-IR). The mean values of magnesium intake were lower than those recommended, without difference between groups (p?>?0.05). All the patients who were evaluated showed adequate mean concentrations of magnesium in the plasma and erythrocyte. The urinary excretion of this mineral was lower than the reference values in both groups and did not show significant difference (p?>?0.05). The values of serum glucose, serum insulin, and HOMA-IR were higher in obese women compared to the control group. A negative correlation was observed between erythrocyte magnesium and glycemic parameters (p?相似文献   

Dietary Fat Is Shunted Away from Oxidation,Toward Storage in Obese Zucker Rats

BESSESEN, DANIEL H, CONNIE L RUPP AND ROBERT H ECKEL. Dietary fat is shunted away from oxidation, toward storage in obese zucker rats. Obes Res. 1995;3:179–189. Previous measurements of lipoprotein lipase (LPL) activity in adipose tissue (ATLPL) of lean and obese Zucker rats have consistently documented increased activity in obese rats relative to lean. Since LPL is considered to be rate limiting for the delivery of triglyceride fatty acids (TGFA) to muscle and adipose tissue, these data have been used to suggest that the metabolic partitioning of TGFA favors storage over oxidation in obese rats. To document the partitioning of TGFA directly, the fate of ¹⁴C labeled oleic acid (42nmols) was fed to lean, obese, and obese Zucker rats fed a hypocaloric diet designed to chronically reduce weight 25% below that of obese controls (reduced-obese). The amount of ¹⁴C recovered in CO₂ over 6 hours following ingestion was significantly less in obese rats compared to lean (0.45 ± 0.06 vs. 0.88 ± 0.09nmols, p=.0004) and less still in the reduced obese group (0.34 ± 0.06nmols p=.00003). Six hours after ingestion, the quantity of label found in adipose tissue was significantly greater in the obese rats compared to lean (14.51 ± 1.92 vs. 1.38 ± 0.29nmols p<.00001), but was intermediate in the reduced-obese group (9.23 ± 0.98nmols p=.0003). At 2.2 hours there was significantly more label in skeletal muscle of lean rats compared to either obese or reduced-obese (2.33 ± 0.24; 1.35 ± 0.04nmols p=.01; 1.41 ± 0.27nm p=.02). However, at 6 hours these differences between groups were no longer present. These findings Indicate that dietary fat is shunted away from oxidation toward storage in obese Zucker rats. Additionally it appears that there may be a relative block in the oxidation of TGFA that is taken up by skeletal muscle in obese rats. Finally the relative normalization of this partitioning defect in reduced-obese rats is at variance with what was suggested by previous measurements of tissue specific levels of LPL, and suggests an enhanced recirculation of fatty acids from adipose tissue to muscle in reduced-obese rats. This could occur through increased delivery of non-esterified fatty acids (NEFA) to muscle as a result of an increase in net lipolysis.     

The Insulin Tolerance Test in Morbidly Obese Patients Undergoing Bariatric Surgery

Objective: To assess the effect of massive weight loss in relation to insulin resistance and its correlation to changes in glycemic homeostasis and lipid profile in severely obese patients. Research Methods and Procedures: A prospective clinical intervention study was carried out with 31 morbidly obese women (body mass index: 54.2 ± 8.8 kg/m²) divided into three groups according to their glucose tolerance test: 14 normal, 8 impaired glucose tolerance, and 9 type 2 diabetes. All subjects underwent an insulin tolerance test with intravenous bolus of 0.1 U insulin/kg body weight before silastic ring vertical gastroplasty Roux‐en‐Y gastric bypass surgery, and again at 2, 4, 6, and 12 months postoperatively. Fasting plasma glucose, hemoglobin A1c, and lipid profile were also evaluated. Results: A reduction of 68 ± 15% in initial excess body weight was evident within 1 year. Along with weight loss, the following statistically significant changes were found: an increase in the insulin‐sensitivity index (Kitt) and a decrease in fasting plasma glucose and hemoglobin A1c, most notably in the type 2 diabetes group. An overall improvement in lipid profile was observed in all three groups. Discussion: Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Significant correlations were found between insulin resistance and metabolic improvements. Weight loss after bariatric surgery induced an improvement in metabolic fitness, related to the reduction in insulin resistance over a range of glucose tolerance statuses from normal to diabetic.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.