Evidence for a major role of skeletal muscle lipolysis in the regulation of lipid oxidation during caloric restriction in vivo.

A lipolytic process in skeletal muscle has recently been demonstrated. However, the physiological importance of this process is unknown. We investigated the role of skeletal muscle lipolysis for lipid utilization during caloric restriction in eight obese women before and after 11 days of very low-calorie diet (VLCD) (2.2 MJ per day). Subjects were studied with indirect calorimetry and microdialysis of skeletal muscle and adipose tissue in order to analyze substrate utilization and glycerol (lipolysis index) in connection with a two-step euglycemic-hyperinsulinemic (12 and 80 mU/m(2). min) clamp. Local blood flow rates in the two tissues were determined with (133)Xe-clearance. Circulating free fatty acids and glycerol decreased to a similar extent during insulin infusion before and during VLCD, and there was a less marked insulin-induced reduction in lipid oxidation during VLCD. Adipose tissue glycerol release was hampered by insulin infusion to the same extent ( approximately 40%) before and during VLCD. Skeletal muscle glycerol release was not influenced by insulin before VLCD. However, during VLCD insulin caused a marked (fivefold) (P < 0.01) increase in skeletal muscle glycerol release. The effect was accompanied by a fourfold stimulation of skeletal muscle blood flow (P < 0.01). We propose that, during short-term caloric restriction, the reduced ability of insulin to inhibit lipids, despite a preserved antilipolytic effect of the hormone in adipose tissue, is caused by an augmented mobilization of fat from skeletal muscle, and that a physiological role of muscle lipolysis provides a local source of fatty acids.     

Changes in Visceral and Subcutaneous Adipose Tissue and Body Composition in Kidney Transplant Recipients at 1, 3, and 5 Years After Kidney Transplant

BackgroundBody composition changes 1 year after kidney transplant (KT) have been studied extensively. However, the number of reports on midterm body composition changes has been limited.MethodsThe medical records and computed tomography scans of 10 living kidney recipients (6 men, 4 women) before KT and at 1, 3, and 5 years post KT were analyzed. Each patient's body mass index was calculated, and the skeletal muscle mass was evaluated using the skeletal muscle mass index and psoas muscle mass index. Each patient's abdominal adipose tissue mass was also quantified by examining the visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratios. These changes were assessed using repeated-measures analysis of variance.ResultsThe body mass index, skeletal muscle mass index, and psoas muscle mass index values did not differ significantly between the pre-KT and 1-, 3-, and 5-year post KT measurements. Conversely, a significant difference was found in the average VAT, SAT, and VAT/SAT ratio values between the pre-KT and at 1, 3, and 5 years post KT (P < .05). The average VAT measurements before and at 1, 3, and 5 years post KT were 66, 94, 108, and 113 cm², respectively, indicating an increasing trend over time.ConclusionsWe observed an increase in the VAT, SAT, and VAT/SAT ratio in patients at 1, 3, and 5 years post KT.     

A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents

The innate immune cell sensor leucine-rich–containing family, pyrin domain containing 3 (NLRP3) inflammasome controls the activation of caspase-1, and the release of proinflammatory cytokines interleukin (IL)-1β and IL-18. The NLRP3 inflammasome is implicated in adipose tissue inflammation and the pathogenesis of insulin resistance. Herein, we tested the hypothesis that adipose tissue inflammation and NLRP3 inflammasome are linked to the downregulation of subcutaneous adipose tissue (SAT) adipogenesis/lipogenesis in obese adolescents with altered abdominal fat partitioning. We performed abdominal SAT biopsies on 58 obese adolescents and grouped them by MRI-derived visceral fat to visceral adipose tissue (VAT) plus SAT (VAT/VAT+SAT) ratio (cutoff 0.11). Adolescents with a high VAT/VAT+SAT ratio showed higher SAT macrophage infiltration and higher expression of the NLRP3 inflammasome–related genes (i.e., TLR4, NLRP3, IL1B, and CASP1). The increase in inflammation markers was paralleled by a decrease in genes related to insulin sensitivity (ADIPOQ, GLUT4, PPARG2, and SIRT1) and lipogenesis (SREBP1c, ACC, LPL, and FASN). Furthermore, SAT ceramide concentrations correlated with the expression of CASP1 and IL1B. Infiltration of macrophages and upregulation of the NLRP3 inflammasome together with the associated high ceramide content in the plasma and SAT of obese adolescents with a high VAT/VAT+SAT may contribute to the limited expansion of the subcutaneous abdominal adipose depot and the development of insulin resistance.     

Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance

Despite extensive studies implicating tumor necrosis factor (TNF)-alpha as a contributing cause of insulin resistance, the mechanism(s) by which TNF-alpha alters energy metabolism in vivo and the tissue specificity of TNF-alpha action are unclear. Here, we investigated the effects of TNF-alpha infusion on gene expression and energy metabolism in adult rats. A 1-day TNF-alpha treatment decreased overall insulin sensitivity and caused a 70% increase (P = 0.005) in plasma levels of free fatty acids (FFAs) and a 46% decrease (P = 0.01) in ACRP30. A 4-day TNF-alpha infusion caused insulin resistance and significant elevation of plasma levels of FFAs and triglycerides and reduction of ACRP30. Plasma glucose concentration was not altered following TNF-alpha infusion for up to 4 days. As revealed by oligonucleotide microarrays, TNF-alpha evoked major and rapid changes in adipocyte gene expression, favoring FFA release and cytokine production, and fewer changes in liver gene expression, but favoring FFA and cholesterol synthesis and VLDL production. There was only a moderate repressive effect on skeletal muscle gene expression. We demonstrate that TNF-alpha antagonizes the actions of insulin, at least in part, through regulation of adipocyte gene expression including reduction in ACRP30 mRNA and induction of lipolysis resulting in increased plasma FFAs. TNF-alpha later alters systemic energy homeostasis that closely resembles the insulin resistance phenotype. Our data suggest that blockade of TNF-alpha action in adipose tissue may prevent TNF-alpha-induced insulin resistance in vivo.     

SIRT1 Transcription Is Decreased in Visceral Adipose Tissue of Morbidly Obese Patients with Severe Hepatic Steatosis

Background  

Visceral adipose tissue is known to release greater amounts of adipokines and free fatty acids into the portal vein, being one of the most predictive factors of nonalcoholic fatty liver disease (NAFLD). Our study has the purpose to evaluate sirtuin 1 (SIRT1), adiponectin, Forkhead/winged helix (FOXO1), peroxisome proliferator-activated receptor (PPAR)γ1–3, and PPARβ/δ mRNA expression in morbidly obese patients in three different lipid depots: visceral (VAT), subcutaneous (SAT), and retroperitoneal (RAT). Recent studies suggest that SIRT1, a NAD⁺-dependent deacetylase, protects rats from NAFLD.     

Subcutaneous and Visceral Adipose Tissue FTO Gene Expression and Adiposity,Insulin Action,Glucose Metabolism,and Inflammatory Adipokines in Type 2 Diabetes Mellitus and in Health

Background  

FTO gene variants are linked to obesity. We tested for site-specific differences in FTO gene expression in subcutaneous and visceral adipose tissue (SAT and VAT, respectively) from individuals with and without type 2 diabetes mellitus (T2D) and the relationships between fasting glucose, in vivo insulin action, and measures of adiposity with FTO gene expression in adipose tissue.     

Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects

Skeletal muscle and adipose tissue lipolysis rates were quantitatively compared in 12 healthy nonobese and 14 insulin-resistant obese subjects for 3.5 h after an oral glucose load using microdialysis measurements of interstitial glycerol concentrations and determinations of local blood flow with 133Xe clearance in the gastrocnemius muscle and in abdominal subcutaneous adipose tissue. Together with measurements of arterialized venous plasma glycerol, the absolute rates of glycerol mobilization were estimated. In the basal state, skeletal muscle and adipose tissue glycerol levels were 50% higher (P < 0.05-0.01) and adipose tissue blood flow (ATBF) and muscle blood flow (MBF) rates were 30-40% lower (P < 0.02-0.05) in obese versus nonobese subjects. After glucose ingestion, adipose tissue glycerol levels were rapidly and transiently reduced, whereas in muscle, a progressive and less pronounced fall in glycerol levels was evident. MBF remained unchanged in both study groups, whereas ATBF increased more markedly (P < 0.01) in the nonobese versus obese subjects after the oral glucose load. The fasting rates of glycerol release per unit of tissue weight from skeletal muscle were between 20 and 25% of that from adipose tissue in both groups. After glucose ingestion, the rates of glycerol release from skeletal muscle and from adipose tissue were almost identical in nonobese and obese subjects. However, the kinetic patterns differed markedly between tissues; in adipose tissue, the rate of glycerol mobilization was suppressed by 25-30% (P < 0.05) after glucose ingestion, whereas no significant reduction was registered in skeletal muscle. We conclude that significant amounts of glycerol are released from skeletal muscle, which suggests that muscle lipolysis provides an important endogenous energy source in humans. In response to glucose ingestion, the regulation of skeletal muscle glycerol release differs from that in adipose tissue; although the rate of glycerol release from adipose tissue is clearly suppressed, the rate of glycerol mobilization from skeletal muscle remains unaltered. In quantitative terms, the rate of glycerol release per unit of tissue weight in adipose tissue and in skeletal muscle is similar in nonobese and obese subjects in both the postabsorptive state and after glucose ingestion.     

Insulin action in muscle and adipose tissue in type 2 diabetes: The significance of blood flow

Under normal metabolic conditions insulin stimulates microvascular perfusion(capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physical exercise.This helps the delivery of insulinitself but also that of substrates and of other signalling molecules to multiple tissues beds and facilitates glucose disposal and lipid kinetics.This effect is impaired in insulin resistance and type 2 diabetes early in the development of metabolic dysregulation and reflects early-onset endothelial dysfunction.Failure of insulin to increase muscle and adipose tissue blood flow results in decreased glucose handling.In fat depots,a blunted postprandial blood flow response will result in an insufficient suppression of lipolysis and an increased spill over of fatty acids in the circulation,leading to a more pronounced insulin resistant state in skeletal muscle.This defect in blood flow response is apparent even in the prediabetic state,implying that it is a facet of insulin resistance and exists long before overt hyperglycaemia develops.The following review intends to summarize the contribution of blood flow impairment to the development of the atherogenic dysglycemia and dyslipidaemia.     

Insulin sensitivity, insulin secretion, and abdominal fat: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study

The relationship between insulin sensitivity and overall obesity is well established. However, there remains debate as to which of the fat depots, visceral abdominal tissue (VAT) or subcutaneous abdominal tissue (SAT), is of greater importance. Also, the relationship between fat distribution and insulin secretion is largely unknown. We studied SI, acute insulin response (AIR), and disposition index (DI), as obtained by minimal model analysis, in 999 Hispanic and 458 African-American men and women as part of the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. VAT and SAT were measured from computed tomography scans performed at the L4/L5 vertebral region. A mixed-model approach was used to determine the relationship between each of the glucose homeostasis measures (SI, AIR, and DI) versus abdominal fat measures. Mean values were as follows: age, 41 years; SI, 1.98 10(-4).min(-1).microU(-1).ml(-1); AIR, 840 pmol.ml(-1).min(-1); BMI, 28.5 kg/m2; VAT, 100 cm2; and SAT, 333 cm2. SAT, VAT, and their joint interaction were each inversely and significantly associated with SI, adjusting for age, sex, ethnicity, and BMI. SAT, but not VAT, was positively associated with AIR, except when additionally adjusting for SI, in which case VAT was inversely associated with AIR. VAT and the joint interaction of VAT and SAT were inversely associated with DI. The fat measures explained 27% of the model R2 for SI, 16% for AIR, and 16% for DI. Thus, fat distribution is an important determinant of both insulin resistance and insulin secretion.     

Oscillations of fatty acid and glycerol release from human subcutaneous adipose tissue in vivo

We sought evidence for pulsatility of lipolysis in human subcutaneous adipose tissue in vivo. Arterialized and adipose tissue venous blood samples were drawn at 2-min intervals from nine healthy subjects. This procedure was repeated during hyperinsulinemic-euglycemic clamp to remove insulin pulsatility. We found evidence for pulsatile release of both nonesterified fatty acids (NEFAs) (seven of nine subjects) and glycerol (five of six subjects) with a period of approximately 12-14 min. This pulsatility was maintained even during the hyperinsulinemic clamp. Checks were made for spurious pulse detection, including the creation of "mock" venoarterialized differences by subtracting one subject's arterialized concentrations from another's venous; the peaks detected were less consistent in character than with real data (peak width, P = 0.006; peak interval, P < 0.004). Significant cross-correlations between NEFA and glycerol release also provided evidence of a real effect. Arterialized norepinephrine concentrations were also pulsatile, but the period did not match that of NEFA and glycerol release. Insulin concentrations were pulsatile with a typical period of 12 min, but this was not significantly cross-correlated with lipolysis. We conclude that release from adipose tissue of the products of lipolysis is pulsatile in humans.     

Increased plasma interleukin 6 concentrations and exaggerated adipose tissue interleukin 6 content in severely obese patients after operative trauma

BACKGROUND: The cytokine response to operative trauma may be altered in obesity. Thus, we monitored changes in systemic and adipose tissue content of interleukin 6 (IL-6) and in insulin resistance in nonobese versus severely obese patients before and immediately after abdominal operations. METHODS: At the beginning and the end of operation, blood samples and biopsies consisting of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were collected from 13 nonobese and 33 severely obese patients. Systemic concentrations of glucose, insulin, and IL-6, as well as adipose tissue content of IL-6, were determined. RESULTS: Plasma IL-6 concentration and adipose tissue content of IL-6 increased, compared with baseline in patients after operation (plasma, 13- and 5.7-fold; VAT, 270- and 210-fold; SAT, 79- and 8.2-fold in severely obese vs nonobese patients, respectively). The increase in IL-6 in plasma and in both VAT and SAT was exaggerated in severely obese patients, compared with nonobese patients. Increases after operation in plasma IL-6 concentrations were correlated positively to the corresponding increases in both SAT and VAT IL-6 content (r = 0.57 and 0.66, respectively). Also, we found a positive correlation between the worsening of insulin resistance and increases in both plasma and SAT IL-6 concentrations (r = 0.40 and 0.51, respectively). CONCLUSIONS: Circulating IL-6 concentrations both at baseline and after operation are related strongly to abdominal adipose tissue content of content of IL-6 and are exaggerated in severely obese persons. After operation, worsening of insulin resistance is associated with increasing plasma and adipose tissue content of IL-6.     

Differential Intra-abdominal Adipose Tissue Profiling in Obese, Insulin-resistant Women

Background

We recently identified differences in abdominal subcutaneous adipose tissue (SAT) from insulin-resistant (IR) as compared to obesity-matched insulin sensitive individuals, including accumulation of small adipose cells, decreased expression of cell differentiation markers, and increased inflammatory activity. This study was initiated to see if these changes in SAT of IR individuals were present in omental visceral adipose tissue (VAT); in this instance, individuals were chosen to be IR but varied in degree of adiposity. We compared cell size distribution and genetic markers in SAT and VAT of IR individuals undergoing bariatric surgery.

Methods

Eleven obese/morbidly obese women were IR by the insulin suppression test. Adipose tissue surgical samples were fixed in osmium tetroxide for cell size analysis via Beckman Coulter Multisizer. Quantitative real-time polymerase chain reaction for genes related to adipocyte differentiation and inflammation was performed.

Results

While proportion of small cells and expression of adipocyte differentiation genes did not differ between depots, inflammatory genes were upregulated in VAT. Diameter of SAT large cells correlated highly with increasing proportion of small cells in both SAT and VAT (r?=?0.85, p?=?0.001; r?=?0.72, p?=?0.01, respectively). No associations were observed between VAT large cells and cell size variables in either depot. The effect of body mass index (BMI) on any variables in both depots was negligible.

Conclusions

The major differential property of VAT of IR women is increased inflammatory activity, independent of BMI. The association of SAT adipocyte hypertrophy with hyperplasia in both depots suggests a primary role SAT may have in regulating regional fat storage.     

Fibronectin Gene Expression in Human Adipose Tissue and Its Associations with Obesity-Related Genes and Metabolic Parameters

Background

Limited data are available on the in vivo expression of fibronectin, one of the main extracellular matrix components. We investigated the expression of fibronectin in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the associations of leptin, adiponectin, and vaspin gene expression with metabolic parameters in obese women.

Methods

We recruited female subjects undergoing bariatric surgery for obesity (n?=?24) and patients undergoing benign gynecological surgery as the control group (n?=?23). We measured anthropometric variables, abdominal fat distribution, metabolic parameters, serum concentrations of leptin, adiponectin, and vaspin, and depot-specific mRNA expression of fibronectin, leptin, adiponectin, and vaspin.

Results

Fibronectin expression in both VAT and SAT was significantly lower in the obese group than in the control group. Fibronectin expression in both VAT and SAT were negatively correlated with body mass index or waist circumference, with higher prominence in VAT. In multiple regression analysis, fibronectin expression in both VAT and SAT was negatively correlated with serum leptin concentration. Fibronectin expression in VAT was negatively correlated with leptin expression in VAT. Additionally, fibronectin expression in SAT was negatively correlated with leptin expression in SAT and positively correlated with adiponectin expression in VAT and SAT.

Conclusions

We found significant negative associations between depot-specific fibronectin expression in human adipose tissue and obesity indices and obesity-related biomarkers. Our results suggest that fibronectin expression may contribute to obesity and metabolic dysregulation in humans.     

Expression of peroxisome proliferator-activated receptor-gamma1 and peroxisome proliferator-activated receptor-gamma2 in visceral and subcutaneous adipose tissue of obese women

Data regarding the expression of peroxisome proliferator-activated receptor (PPAR)-gamma(1) and PPAR-gamma(2) in human visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are conflicting. To clarify this issue, we studied 50 women who had a BMI >35 kg/m(2) were undergoing gastric reduction surgery. Phenotyping included recording of anthropometric parameters and of a biological profile. Quantification of the expression of PPAR-gamma(1) and PPAR-gamma(2) in samples of VAT and SAT was performed by real-time RT-PCR. In both SAT and VAT, the level of expression of PPAR-gamma(2) were >20-fold that of PPAR-gamma(1) (P < 0.001 for both). However, only PPAR-gamma(1) was differentially expressed, its levels in SAT being 216 +/- 34% those in VAT (P < 0.001). In a stepwise, multivariate regression analysis, the levels of PPAR-gamma(1) in both SAT and VAT were the major determinants of waist circumference (R(2) = 21% for both; P < 0.01). Finally, leptin but not PPARs appeared as the single parameter explaining the largest part of the variability of BMI in our cohort of patients (R(2) = 22%, P < 0.001). These results are consistent with the putative roles of PPAR-gamma(1) and PPAR-gamma(2) in carbohydrate metabolism and energy homeostasis, respectively. As such, they constitute an important step toward the identification of potential targets for novel therapeutic strategies in the fields of obesity.     

Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients: is cellular insulin resistance a secondary phenomenon?

To elucidate potential mechanisms for insulin resistance occurring early in the development of type 2 diabetes, we studied 10 young healthy individuals, each with two first-degree relatives with type 2 diabetes, and 10 control subjects without known type 2 diabetic relatives. They were pairwise matched for age (35 +/- 1 vs. 35 +/- 1 years), BMI (23.6 +/- 0.6 vs. 23.1 +/- 0.4 kg/m2), and sex (four men, six women). Glucose turnover was assessed during a euglycemic clamp at two insulin levels (low approximately 20 mU/l; high approximately 90 mU/l), and abdominal subcutaneous adipose tissue (SAT) lipolysis and blood flow were concomitantly studied with microdialysis and 133Xe clearance. HbA1c was higher in patients with type 2 diabetic relatives than in control subjects (4.8 +/- 0.1 vs. 4.5 +/- 0.1%, P < 0.02), but fasting glucose, insulin, and C-peptide levels were similar. During the clamp, the insulin sensitivity index for glucose disposal was lower (P < 0.03) in relatives than in control subjects (low 12.0 +/- 1.6 vs. 18.1 +/- 1.4; high 9.4 +/- 0.8 vs. 12.9 +/- 0.6 [100 x mg x l x kg(-1) x mU(-1) x min(-1)]). This difference was partially attributed to slightly higher clamp insulin levels in the relatives (P < 0.03), suggesting an impaired rate for insulin clearance. SAT lipolysis measured as in situ glycerol release did not differ under basal conditions (2.0 +/- 0.2 vs. 2.1 +/- 0.2 micromol x kg(-1) x min(-1)), but the suppression during the insulin infusion was less marked in relatives than in control subjects (glycerol release: low 0.92 +/- 0.09 vs. 0.68 +/- 0.16; high 0.71 +/- 0.10 vs. 0.34 +/- 0.10 micromol x kg(-1) x min(-1); P < 0.03). Plasma nonesterified fatty acids also tended to be higher in relatives than in control subjects during the insulin infusion (NS). In contrast, in vitro experiments with isolated subcutaneous adipocytes displayed similar effects of insulin in relatives and control subjects with respect to both glucose uptake and antilipolysis. In conclusion, insulin action in vivo on both lipolysis and glucose uptake is impaired early in the development of type 2 diabetes. Since this impairment was not found in isolated adipocytes, it may be suggested that neural or hormonal perturbations precede cellular insulin resistance in type 2 diabetes.     

Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis

Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with alpha/beta hydrolase folds, the GXSXG motif for serine esterase and the His-Gly dipeptide motif, has provided a previously unannotated gene that is induced during 3T3-L1 adipocytic differentiation. Because of its remarkable structural resemblance to triacylglycerol hydrolase (TGH) with 70.4% identity, we have tentatively designated this enzyme as TGH-2 and the original TGH as TGH-1. TGH-2 is also similar to TGH-1 in terms of tissue distribution, subcellular localization, substrate specificity, and regulation. Both enzymes are predominantly expressed in liver, adipose tissue, and kidney. In adipocytes, they are localized in microsome and fatcake. Both enzymes hydrolyzed p-nitophenyl butyrate, triolein, and monoolein but not diolein, cholesteryl oleate, or phospholipids; hydrolysis of short-chain fatty acid ester was 30,000-fold more efficient than that of long-chain fatty acid triacylglycerol. Fasting increased the expression of both genes in white adipose tissue, whereas refeeding suppressed their expression. RNA silencing of TGH-2 reduced isoproterenol-stimulated glycerol release by 10% in 3T3-L1 adipocytes, while its overexpression increased the glycerol release by 20%. Thus, TGH-2 may make a contribution to adipocyte lipolysis during period of increased energy demand.     

Relationship between abdominal fat and bone mineral density in white and African American adults

Several studies have documented relationships between adipose tissue and bone mineral density (BMD); however, the degree to which there are racial differences in this relationship is not known. The purpose of this study was to examine the relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and BMD among white and African American adults. The sample included 330 white women, 328 African American women, 307 white men, and 116 African American men 18-74 years of age. Dual-energy X-ray absorptiometry scans were used to measure BMD and computed tomography scans were used to measure abdominal VAT and SAT. Linear regression was used to assess the relationships between abdominal adiposity and BMD and to explore possible sex and race differences in the associations. In the total sample as well as in all sex-by-race groups, VAT and SAT were negatively related to BMD, after adjustment for lean body mass (LBM) and several covariates. The VAT model (including covariates) explained 33.3% of the variance in BMD and the SAT model (including covariates) explained 32.7% of the variance in BMD. Being African American, being male, and having high LBM were all associated with higher BMD. Race and sex interactions were not significant, indicating that the relationships were similar across race and sex groups. In conclusion, BMD was inversely related to abdominal VAT and SAT in white and African American adults after adjustment for LBM.     

Extreme insulin resistance of the central adipose depot in vivo

Despite the well-described association between obesity and insulin resistance, the physiologic mechanisms that link these two states are poorly understood. The present study was performed to elucidate the role of visceral adipose tissue in whole-body glucose homeostasis. Dogs made abdominally obese with a moderately elevated fat diet had catheters placed into the superior mesenteric artery so that the visceral adipose bed could be insulinized discretely. Omental insulin infusion was extracted at approximately 27%, such that systemic insulin levels were lower than in control (portal vein) insulin infusions. Omental infusion did not lower systemic free fatty acid levels further than control infusion, likely because of the resistance of the omental adipose tissue to insulin suppression and the confounding lower systemic insulin levels. The arteriovenous difference technique showed that local infusion of insulin did suppress omental lipolysis, but only at extremely high insulin concentrations. The median effective dose for suppression of lipolysis was almost fourfold higher in the visceral adipose bed than for whole-body suppression of lipolysis. Thus, the omental adipose bed represents a highly insulin-resistant depot that drains directly into the portal vein. Increased free fatty acid flux to the liver may account for hepatic insulin resistance in the moderately obese state.