Abdominal adiposity and insulin resistance in obese men

We examined the independent relationships among various visceral and abdominal subcutaneous adipose tissue (AT) depots, glucose tolerance, and insulin sensitivity in 89 obese men. Measurements included an oral glucose tolerance test (OGTT), glucose disposal by euglycemic clamp, and abdominal and nonabdominal (e.g., peripheral) AT by magnetic resonance imaging (MRI). OGTT glucose and glucose disposal rates were related (P < 0.05) to visceral AT (r = 0.50 and -0.41, respectively). These observations remained significant (P < 0.05) after control for nonabdominal and abdominal subcutaneous AT, and maximal O(2) consumption (VO(2 max)). Abdominal subcutaneous AT was not a significant correlate (P > 0.05) of any metabolic variable after control for nonabdominal and visceral AT and VO(2 max). Division of abdominal subcutaneous AT into deep and superficial depots and visceral AT into intra- and extraperitoneal AT depots did not alter the observed relationships. Further analysis matched two groups of men for abdominal subcutaneous AT but also for low and high visceral AT. Men with high visceral AT had higher OGTT glucose values and lower glucose disposal rates compared with those with low visceral AT values (P < 0.05). A similar analysis performed on two groups of men matched for visceral AT but also for high and low abdominal subcutaneous AT revealed no statistically different values for any metabolic variable (P > 0.10). In conclusion, visceral AT alone is a strong correlate of insulin resistance independent of nonabdominal and abdominal subcutaneous AT and cardiovascular fitness. Subdivision of visceral and abdominal subcutaneous AT by MRI did not provide additional insight into the relationship between abdominal obesity and metabolic risk in obese men.     

Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance

Whereas truncal (central) adiposity is strongly associated with the insulin resistant metabolic syndrome, it is uncertain whether this is accounted for principally by visceral adiposity (VAT). Several recent studies find as strong or stronger association between subcutaneous abdominal adiposity (SAT) and insulin resistance. To reexamine the issue of truncal adipose tissue depots, we performed cross-sectional abdominal computed tomography, and we undertook the novel approach of partitioning SAT into the plane superficial to the fascia within subcutaneous adipose tissue (superficial SAT) and that below this fascia (deep SAT), as well as measurement of VAT. Among 47 lean and obese glucose-tolerant men and women, insulin-stimulated glucose utilization, measured by euglycemic clamp, was strongly correlated with both VAT and deep SAT (r = -0.61 and -0.64, respectively; both P < 0.001), but not with superficial SAT (r = -0.29, not significant). Also, VAT and deep SAT followed a highly congruent pattern of associations with glucose and insulin area under the curve (75-g oral glucose tolerance test), mean arterial blood pressure, apoprotein-B, high-density lipoprotein cholesterol, and triglyceride. Superficial SAT had markedly weaker association with all these parameters and instead followed the pattern observed for thigh subcutaneous adiposity. We conclude that there are two functionally distinct compartments of adipose tissue within abdominal subcutaneous fat and that the deep SAT has a strong relation to insulin resistance.     

Visceral fat and liver fat are independent predictors of metabolic risk factors in men

We examined the independent associations among abdominal adipose tissue (AT), liver fat, cardiorespiratory fitness (CRF), and lipid variables in 161 Caucasian men who had a wide variation in adiposity. We measured AT and liver fat by computed tomography and CRF by a maximal exercise test on a treadmill. Visceral AT remained a significant (P or= 0.05) correlate of any lipid variable after control for visceral AT and CRF. Furthermore, subdivision of subcutaneous AT into deep and superficial depots did not alter these observations. Visceral AT was the strongest correlate of liver fat and remained so after control for abdominal subcutaneous AT, CRF, and alcohol consumption (r = -0.34, P < 0.01). In contrast, abdominal subcutaneous AT and CRF were not significant (P > 0.10) correlates of liver fat after control for visceral AT. Visceral AT remained a significant (P < 0.01) correlate of TG, HDL-C, and TC/HDL-C independent of liver fat. However, liver fat was also a significant correlate (P 相似文献   

Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus

We examined the relationship between peripheral/hepatic insulin sensitivity and abdominal superficial/deep subcutaneous fat (SSF/DSF) and intra-abdominal visceral fat (VF) in patients with type 2 diabetes mellitus (T2DM). Sixty-two T2DM patients (36 males and 26 females, age = 55 +/- 3 yr, body mass index = 30 +/- 1 kg/m2) underwent a two-step euglycemic insulin clamp (40 and 160 mU. m(-2). min(-1)) with [3-3H]glucose. SSF, DSF, and VF areas were quantitated with magnetic resonance imaging at the L(4-5) level. Basal endogenous glucose production (EGP), hepatic insulin resistance index (basal EGP x FPI), and total glucose disposal (TGD) during the first and second insulin clamp steps were similar in male and female subjects. VF (159 +/- 9 vs. 143 +/- 9 cm2) and DSF (199 +/- 14 vs. 200 +/- 15 cm(2)) were not different in male and female subjects. SSF (104 +/- 8 vs. 223 +/- 15 cm2) was greater (P < 0.0001) in female vs. male subjects despite similar body mass index (31 +/- 1 vs. 30 +/- 1 kg/m2) and total body fat mass (31 +/- 2 vs. 33 +/- 2 kg). In male T2DM, TGD during the first insulin clamp step (1st TGD) correlated inversely with VF (r = -0.45, P < 0.01), DSF (r = -0.46, P < 0.01), and SSF (r = -0.39, P < 0.05). In males, VF (r = 0.37, P < 0.05), DSF (r = 0.49, P < 0.01), and SSF (r = 0.33, P < 0.05) were correlated positively with hepatic insulin resistance. In females, the first TGD (r = -0.45, P < 0.05) and hepatic insulin resistance (r = 0.49, P < 0.05) correlated with VF but not with DSF, SSF, or total subcutaneous fat area. We conclude that visceral adiposity is associated with both peripheral and hepatic insulin resistance, independent of gender, in T2DM. In male but not female T2DM, deep subcutaneous adipose tissue also is associated with peripheral and hepatic insulin resistance.     

Elevated plasma nonesterified fatty acids are associated with deterioration of acute insulin response in IGT but not NGT

High concentrations of nonesterified fatty acids (NEFA) are a risk factor for developing type 2 diabetes in Pima Indians. In vitro and in vivo, chronic elevation of NEFA decreases glucose-stimulated insulin secretion. We hypothesized that high fasting plasma NEFA would increase the risk of type 2 diabetes by inducing a worsening of glucose-stimulated insulin secretion in Pima Indians. To test this hypothesis, fasting plasma NEFA concentrations, body composition, insulin action (M), acute insulin response (AIR, 25-g IVGTT), and glucose tolerance (75-g OGTT) were measured in 151 Pima Indians [107 normal glucose tolerant (NGT), 44 impaired glucose tolerant (IGT)] at the initial visit. These subjects, participants in ongoing studies of the pathogenesis of obesity and type 2 diabetes, had follow-up measurements of body composition, glucose tolerance, M, and AIR. In NGT individuals, cross-sectionally, high fasting plasma NEFA concentrations at the initial visit were negatively associated with AIR after adjustment for age, sex, percent body fat, and M (P = 0.03). Longitudinally, high fasting plasma NEFA concentrations at the initial visit were not associated with change in AIR. In individuals with IGT, cross-sectionally, high fasting plasma NEFA concentrations at the initial visit were not associated with AIR. Longitudinally, high fasting plasma NEFA concentrations at the initial visit were associated with a decrease in AIR before (P < 0.0001) and after adjustment for sex, age at follow-up, time of follow-up, change in percent body fat and insulin sensitivity, and AIR at the initial visit (P = 0.0006). In conclusion, findings in people with NGT indicate that fasting plasma NEFA concentrations are not a primary etiologic factor for beta-cell failure. However, in subjects who have progressed to a state of IGT, chronically elevated NEFA seem to have a deleterious effect on insulin-secretory capacity.     

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.     

Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity

Expansion of adipose tissue mass results from increased number and size of adipocyte cells. We hypothesized that subcutaneous abdominal preadipocytes in obese individuals might have an intrinsically higher propensity to differentiate into adipocytes. Thus we investigated the relationship between obesity and the level of in vitro preadipocyte differentiation in Pima Indians. Subcutaneous abdominal stromal vascular fractions containing preadipocytes were cultured from 58 nondiabetic subjects [31 M/27 F, 30 +/- 6 yr, body fat 34 +/- 8% by dual-energy X-ray absorptiometry (means +/- SD)]. The average percentage of preadipocyte differentiation (PDIFF; cell count by microscopy) was 11 +/- 11% (range 0.2-51%). PDIFF correlated negatively with percent body fat (r = -0.35, P = 0.006) and waist circumference (r = -0.45, P = 0.0004). Multiple regression analysis indicated that waist circumference (P = 0.01), sex (P = 0.01), and percent body fat (P = 0.05) were significant determinants of PDIFF. Molecular characterization of predifferentiated cultured cells was performed by real-time PCR measurements of glucocorticoid receptor-alpha (GRalpha), insulin-like growth factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-gamma (PPARgamma), enhancer-binding protein GATA-3, CCAAT/enhancer-binding protein-alpha undifferentiated protein (CUP/AP-2alpha), and endothelial cell-specific marker 2 (ECSM2). The mRNA concentrations of GRalpha correlated with PDIFF (r = 0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPARgamma, r = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2alpha, r = -0.2, P = 0.1; ECSM2, r = 0.04, P = 0.7). Contrary to our hypothesis, the results may indicate a blunted in vitro differentiation potential of preadipocytes in centrally obese individuals. The lower differentiation potential of preadipocytes in the obese subjects might be due, at least partly, to decreased glucocorticoid receptor expression.     

Dietary Calcium Intake Is Associated With Less Gain in Intra‐Abdominal Adipose Tissue Over 1 Year

Calcium intake is reported to enhance weight loss with a preferential loss in trunk fat. Discrepant findings exist as to the effects of calcium intake on longitudinal changes in total fat mass and central fat deposition. Therefore, the purpose of this study was to determine associations between dietary calcium intake and 1‐year change in body composition and fat distribution, specifically intra‐abdominal adipose tissue (IAAT). A total of 119 healthy, premenopausal women were evaluated at baseline and 1 year later. Average dietary calcium was determined via 4‐day food records. Total fat was determined by dual‐energy X‐ray absorptiometry (DXA) and subcutaneous abdominal adipose tissue (SAAT) and IAAT by computed tomography. Over the study period, participants' reported daily calcium and energy intakes were 610.0 ± 229.9 mg and 1,623.1 ± 348.5 kcal, respectively. The mean change in weight, total fat, IAAT, and SAAT was 4.9 ± 4.4 kg, 5.3 ± 4.0 kg, 7.7 ± 19.5 cm², and 49.3 ± 81.1 cm², respectively. Average calcium intake was significantly, inversely associated with 1‐year change in IAAT (standardized β: ?0.23, P < 0.05) after adjusting for confounding variables. For every 100 mg/day of calcium consumed, gain in IAAT was reduced by 2.7 cm². No significant associations were observed for average calcium intake with change in weight, total fat, or SAAT. In conclusion, dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women. Further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution.     

Association of Breakfast Skipping With Visceral Fat and Insulin Indices in Overweight Latino Youth

Few studies have investigated the relationship between breakfast consumption and specific adiposity or insulin dynamics measures in children. The goal of this study is to determine whether breakfast consumption is associated with adiposity, specifically intra‐abdominal adipose tissue (IAAT), and insulin dynamics in overweight Latino youth. Participants were a cross‐sectional sample of 93 overweight (≥85th percentile BMI) Latino youth (10–17 years) with a positive family history of type 2 diabetes. Dietary intake was assessed by two 24‐h recalls, IAAT, and subcutaneous abdominal adipose tissue (SAAT) by magnetic resonance imaging, body composition by dual energy X‐ray absorptiometry, and insulin dynamics by a frequently sampled intravenous glucose tolerance test and minimal modeling. Participants were divided into three breakfast consumption categories: those who reported not eating breakfast on either day (breakfast skippers; n = 20), those who reported eating breakfast on one of two days (occasional breakfast eaters; n = 39) and those who ate breakfast on both days (breakfast eaters; n = 34). Using analyses of covariance, breakfast omission was associated with increased IAAT (P = 0.003) independent of age, Tanner, sex, total body fat, total body lean tissue mass, and daily energy intake. There were no significant differences in any other adiposity measure or in insulin dynamics between breakfast categories. Eating breakfast is associated with lower visceral adiposity in overweight Latino youth. Interventions focused on increasing breakfast consumption are warranted.     

Familiality of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in Pima Indians.

Susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) is largely genetically determined. In Pima Indians, obesity, insulin resistance, and a low acute insulin response (AIR) to an intravenous glucose infusion are each predictors of the disease. To ascertain whether these phenotypes are genetically determined, we estimated their familiality in nondiabetic Pima Indians with a maximum-likelihood method. Percentage body fat (PFAT) was highly familial (h2 =.76), whereas waist/ thigh circumference ratio (W/T ratio) was not significantly familial after controlling for PFAT (h2 = .16). AIR was also highly familial (h2 = .80 at 10 min), even after controlling for PFAT and insulin action (h2 = .70). Insulin action at physiologic plasma insulin concentrations was familial (h2 = .61) but less so after controlling for PFAT and W/T ratio (h2 = .38). At maximally stimulating insulin concentrations, insulin action was familial (h2 = .45) and was less influenced by controlling for PFAT and W/T ratio (h2 = .49). We conclude that in Pima Indians (1) PFAT and AIR are highly familial traits, (2) central distribution of fat is not a familial trait when controlled for PFAT, (3) 38%-49% of the variance in insulin action, independent of the effect of obesity, is familial, and (4) PFAT, AIR, and insulin action are useful traits to study genetic susceptibility to NIDDM. Because genetic parameter estimates are applicable only to the populations from which they were estimated, it is important to determine whether these estimates of familialities in Pima Indians can be confirmed in other populations before the utility of these traits in searching for NIDDM susceptibility genes in those populations can be fully advocated.     

Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU x m(-2) x min(-1)) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-D-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 +/- 0.4 vs. 2.3 +/- 0.5 micromol x kg tissue(-1) x min(-1), P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal (r2 = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area (r = -0.75, P = 0.008), and whole body glucose disposal (r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.     

The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat

Individual compartments of abdominal adiposity and lipid content within the liver and muscle are differentially associated with metabolic risk factors, obesity and insulin resistance. Subjects with greater intra-abdominal adipose tissue (IAAT) and hepatic fat than predicted by clinical indices of obesity may be at increased risk of metabolic diseases despite their "normal" size. There is a need for accurate quantification of these potentially hazardous depots and identification of novel subphenotypes that recognize individuals at potentially increased metabolic risk. We aimed to calculate a reference range for total and regional adipose tissue (AT) as well as ectopic fat in liver and muscle in healthy subjects. We studied the relationship between age, body-mass, BMI, waist circumference (WC), and the distribution of AT, using whole-body magnetic resonance imaging (MRI), in 477 white volunteers (243 male, 234 female). Furthermore, we used proton magnetic resonance spectroscopy (MRS) to determine intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid content. The anthropometric variable which provided the strongest individual correlation for adiposity and ectopic fat stores was WC in men and BMI in women. In addition, we reveal a large variation in IAAT, abdominal subcutaneous AT (ASAT), and IHCL depots not fully predicted by clinically obtained measurements of obesity and the emergence of a previously unidentified subphenotype. Here, we demonstrate gender- and age-specific patterns of regional adiposity in a large UK-based cohort and identify anthropometric variables that best predict individual adiposity and ectopic fat stores. From these data we propose the thin-on-the-outside fat-on-the-inside (TOFI) as a subphenotype for individuals at increased metabolic risk.     

Relation of the White Blood Cell Count to Obesity and Insulin Resistance: Effect of Race and Gender

PRATLEY, RICHARD E, CHARLTON WILSON AND CLIFTON BOGARDUS. Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender. Obes Res. Recent reports suggest that the white blood cell (WBC) count is related to plasma insulin concentrations and insulin resistance in healthy individuals. The present study examines whether these relations are independent of obesity and the pattern of body fat distribution and tests whether race and gender affect these relations. WBC counts, insulin responses to a 75 gram oral glucose tolerance test (OGTT) and glucose disposal during a two-step hyperinsulinemic euglycemic clamp were measured in 300 men and women (149 Pima Indians, 100 whites, and 51 blacks) with a wide range of obesity. WBC counts were lower in blacks than Pima Indians or whites and tended to be higher in women than men. The subgroups were comparable in age and body weight, but percent body fat and plasma insulin concentrations were higher and glucose disposal during the glucose clamp was lower in Pima Indians than in blacks or whites. In the group as a whole, the WBC count correlated with obesity (body mass index and percent body fat), the waist to thigh ratio (an index of the pattern of body fat distribution), and plasma insulin concentrations and was negatively related to age and glucose disposal during the clamp. In multiple regression analyses, only age, race and obesity were significantly associated with the WBC count. When the analyses were restricted to Pima men, in whom correlations between the WBC count and the metabolic variables appeared the strongest, the WBC count remained significantly associated with plasma insulin concentrations, but not glucose disposal, after controlling for age and obesity. The results of this study indicate that age, race, and obesity are significantly associated with the WBC count in healthy individuals. Plasma insulin concentrations, but not insulin resistance per se, may also be weakly associated with the WBC count, but this may be population specific.     

In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue

We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdominal adipose tissues and in the preperitoneal adipose tissue in the round ligament were measured by microdialysis and (133)Xe washout under basal, postabsorptive conditions and during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the basal state and during epinephrine stimulation, the superficial subcutaneous adipose tissue had higher interstitial glycerol concentrations than the two other depots. Similarly, the calculated glycerol outputs from the superficial depot were significantly higher than those from the deep subcutaneous and the preperitoneal depots. Thus, it is concluded that the lipolytic rate of the superficial subcutaneous adipose tissue on the anterior abdominal wall is higher than that of the deep subcutaneous adipose tissue on the posterior abdominal wall and that of the preperitoneal adipose tissue in the round ligament.     

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.     

Relationships Between Changes in Body Composition and Changes in Cardiovascular Risk Factors: The SOS Intervention Study

SJÖSTRÖM, C DAVID, LAUREN LISSNER, LARS SJÖSTROM. Relationships between changes in body composition and changes in cardiovascular risk factors: The SOS Intervention Study. Relationships between 2-year changes in body composition (estimated from computed tomography-validated anthropometry based on sagittal trunk diameter, weight, and height), adipose tissue (AT) distribution, and cardiovascular risk factors (blood pressure, lipids, glucose, insulin, uric acid) were examined in 842 treated adults with severe obesity with weight changes from ?95. 5 to +30. 6 kg. Although the change (Δ) of visceral AT mass (expressed in % total AT) for a given change in body mass index (ΔBMI) was 6-fold larger in men than in women, Δwaist and Δwaist/hip were similar in both sexes. In men, risk factor changes were similarly related to Awaist, Abodyweight, and ΔBMI, whereas in women, Δbodyweight seemed to be the single independent variable with the highest explanatory power. In multivariate regressions adjusted for ΔBMI and baseline conditions, Δvisceral AT mass was more strongly associated with risk factor changes than were Δwaist and ?waist/hip. When using a three-compartment model (lean body mass, subcutaneous and visceral AT masses) plus neck and thigh girths (indicators of subcutaneous AT distribution), risk factor changes were related both to ?subcutaneous and ?visceral AT masses but not to Δlean body mass. In agreement with cross-sectional findings, Δneck was positively and Δthigh was negatively related to some risk factor changes. Thus, the use of waist as a single risk factor indicator seems less effective for epidemiological studies than the simple anthropometric measures presented here, which are able to separate the effects of visceral AT mass, subcutaneous AT mass, and subcutaneous AT distribution on metabolic parameters under both cross-sectional and longitudinal conditions.     

11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance

Objective: Increased mRNA and activity levels of 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11βHSD1 expression or activity in abdominal subcutaneous AT of non‐diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA‐IR)]. Research Methods and Procedures: Prospective analyses were performed in 20 subjects (two whites and 18 Pima Indians) who had baseline measurements of 11βHSD1 mRNA and activity in whole AT (follow‐up, 0.3 to 4.9 years) and in 47 Pima Indians who had baseline assessments of 11βHSD1 mRNA in isolated adipocytes (follow‐up, 0.8 to 5.3 years). Results: In whole AT, although 11βHSD1 mRNA levels showed positive associations with changes in weight and HOMA‐IR, 11βHSD1 activity was associated with changes in HOMA‐IR but not in body weight. 11βHSD1 mRNA levels in isolated adipocytes were not associated with follow‐up changes in any of the anthropometric or metabolic variables. Discussion: Our results indicate that increased expression of 11βHSD1 in subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin resistance. This prospective relationship does not seem to be mediated by increased 11βHSD1 expression in adipocytes.     

Age-Related Different Relationships between Ectopic Adipose Tissues and Measures of Central Obesity in Sedentary Subjects

Accumulation of fat at ectopic sites has been gaining attention as pivotal contributor of insulin resistance, metabolic syndrome and related cardiovascular complications. Intermuscular adipose tissue (IMAT), located between skeletal muscle bundles and beneath muscle fascia, has been linked to physical inactivity, ageing and body mass index, but little is known about its relationship with the other AT compartments, in particular with increasing age. To address this issue, erector spinae IMAT, epicardial (EAT), intraabdominal (IAAT) and abdominal subcutaneous adipose tissue (SAT) were simultaneously measured by Magnetic Resonance Imaging (MRI) and related to waist circumference measurements and age in 32 sedentary subjects without cardiovascular disease (18 men; 14 women; mean age 48.5±14 years). Fasting glucose, triglycerides and HDL-cholesterol were also assessed. We observed that, after dividing individuals according to age (≤ or >50 years), IMAT and EAT depots were significantly more expanded in older subjects (63.2±8.3 years) than in the younger ones (38.4±5.2 years) (p<0.001). Overall, both IMAT and EAT showed stronger positive associations with increasing age (β = 0.63 and 0.67, respectively, p<0.001 for both) than with waist circumference (β = 0.55 and 0.49, respectively, p<0.01 for both) after adjusting for gender. In addition, the gender-adjusted associations of IMAT and EAT with waist circumference and IAAT were significant in individuals ≤50 years only (p<0.05 for all) and not in the older ones. In contrast, no age-related differences were seen in the relationships of IAAT and SAT with waist circumference. Finally, serum triglycerides levels turned out not to be independently related with ectopic IMAT and EAT. In conclusion, the expansion of IMAT and EAT in sedentary subjects is more strongly related to age than waist circumference, and a positive association of these ectopic depots with waist circumference and IAAT amount can be postulated in younger individuals only.     

Adipose tissue volume measured by magnetic resonance imaging and computerized tomography in rats

The primary purpose of this study was to investigate the viability of magnetic resonance imaging (MRI) as a means of measuring the body composition of rodents. To do so we compared adipose tissue (AT) volumes measured by MRI with those obtained by X-ray computerized tomography (CT) in a group of rats (n = 17) varying in weight (465-815 g) and percent body fat (5.4-31.1%), with the latter determined by chemical analysis. For both MRI and CT, AT volumes (cm3) per transverse slice (3-mm thickness, 21-mm centers) were determined using a computer-based image analysis system that permitted detailed comparisons of both visceral and subcutaneous AT depots. Total AT volumes were calculated using a linear interpolation of AT areas obtained on consecutive slices. Correlation coefficients between MRI and CT for visceral [r = 0.98, standard error of estimate (SEE) = 6.8 cm3], subcutaneous (r = 0.98, SEE = 6.5 cm3), and total AT volumes (r = 0.99, SEE = 9.0 cm3) were highly significant (P less than 0.001). Both MRI- and CT-predicted AT mass (assuming fat density = 0.90 g/ml) correlated strongly with chemically extracted lipid (grams) values (r = 0.98, SEE 9.6 g and r = 0.99, SEE = 6.9 g, respectively). Post hoc Scheffé contrasts demonstrated that the mean AT and lipid mass values derived by the three methods were not significantly different (P = 0.01). No systematic differences were observed because the regression lines derived for either MRI or CT vs. chemical analysis were not significantly different from the identity line.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT

We have separated the effect of insulin on glucose distribution/transport, glucose disposal, and endogenous production (EGP) during an intravenous glucose tolerance test (IVGTT) by use of a dual-tracer dilution methodology. Six healthy lean male subjects (age 33 +/- 3 yr, body mass index 22.7 +/- 0.6 kg/m(2)) underwent a 4-h IVGTT (0.3 g/kg glucose enriched with 3-6% D-[U-(13)C]glucose and 5-10% 3-O-methyl-D-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg of D-[U-(13)C]glucose and 8 mg/kg of 3-O-methyl-D-glucose). A new model described the kinetics of the two glucose tracers and native glucose with the use of a two-compartment structure for glucose and a one-compartment structure for insulin effects. Insulin sensitivities of distribution/transport, disposal, and EGP were similar (11.5 +/- 3.8 vs. 10.4 +/- 3.9 vs. 11.1 +/- 2.7 x 10(-2) ml small middle dot kg(-1) small middle dot min(-1) per mU/l; P = nonsignificant, ANOVA). When expressed in terms of ability to lower glucose concentration, stimulation of disposal and stimulation of distribution/transport accounted each independently for 25 and 30%, respectively, of the overall effect. Suppression of EGP was more effective (P < 0.01, ANOVA) and accounted for 50% of the overall effect. EGP was suppressed by 70% (52-82%) (95% confidence interval relative to basal) within 60 min of the IVGTT; glucose distribution/transport was least responsive to insulin and was maximally activated by 62% (34-96%) above basal at 80 min compared with maximum 279% (116-565%) activation of glucose disposal at 20 min. The deactivation of glucose distribution/transport was slower than that of glucose disposal and EGP (P < 0.02) with half-times of 207 (84-510), 12 (7-22), and 29 (16-54) min, respectively. The minimal-model insulin sensitivity was tightly correlated with and linearly related to sensitivity of EGP (r = 0.96, P < 0.005) and correlated positively but nonsignificantly with distribution/transport sensitivity (r = 0.73, P = 0.10) and disposal sensitivity (r = 0.55, P = 0.26). We conclude that, in healthy subjects during an IVGTT, the two peripheral insulin effects account jointly for approximately one-half of the overall insulin-stimulated glucose lowering, each effect contributing equally. Suppression of EGP matches the effect in the periphery.