Preferential reductions in intermuscular and visceral adipose tissue with exercise-induced weight loss compared with calorie restriction

Intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) are associated with insulin resistance. We sought to determine whether exercise-induced weight loss (EX) results in greater reductions in IMAT and VAT compared with similar weight loss induced by calorie restriction (CR) and whether these changes are associated with improvements in glucoregulation. Sedentary men and women (50-60 yr; body mass index of 23.5-29.9 kg/m(2)) were randomized to 1 yr of CR (n = 17), EX (n = 16), or a control group (CON; n = 6). Bilateral thigh IMAT and VAT volumes were quantified using multi-slice magnetic resonance imaging. Insulin sensitivity index (ISI) was determined from oral glucose tolerance test glucose and insulin levels. Weight loss was comparable (P = 0.25) in the CR (-10.8 ± 1.4%) and EX groups (-8.3 ± 1.5%) and greater than in the control group (-2.0 ± 2.4%; P < 0.05). IMAT and VAT reductions were larger in the CR and EX groups than in the CON group (P ≤ 0.05). After controlling for differences in total fat mass change between the CR and EX groups, IMAT and VAT reductions were nearly twofold greater (P ≤ 0.05) in the EX group than in the CR group (IMAT: -45 ±5 vs. -25 ± 5 ml; VAT: -490 ± 64 vs. -267 ± 61 ml). In the EX group, the reductions in IMAT were correlated with increases in ISI (r = -0.71; P = 0.003), whereas in the CR group, VAT reductions were correlated with increases in ISI (r = -0.64; P = 0.006). In conclusion, calorie restriction and exercise-induced weight loss both decrease IMAT and VAT volumes. However, exercise appears to result in preferential reductions in these fat depots.     

Intermuscular adipose tissue-free skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in adults.

Skeletal muscle (SM) is a large and physiologically important compartment. Adipose tissue is found interspersed between and within SM groups and is referred to as intermuscular adipose tissue (IMAT). The study objective was to develop prediction models linking appendicular lean soft tissue (ALST) estimates by dual-energy X-ray absorptiometry (DXA) with whole body IMAT-free SM quantified by magnetic resonance imaging. ALST and total-body IMAT-free SM were evaluated in 270 healthy adults [body mass index (BMI) of <35 kg/m(2)]. The SM prediction models were then validated by the leave-one-out method and by application in a new group of subjects who varied in SM mass [anorexia nervosa (AN), n = 23; recreational athletes, n = 16; patients with acromegaly, n = 7]. ALST alone was highly correlated with whole body IMAT-free SM [model 1: R(2) = 0.96, standard error (SE) = 1.46 kg, P < 0.001]; age (model 2: R(2) = 0.97, SE = 1.38 kg, P < 0.001) and sex and race (model 3: R(2) = 0.97, SE = 1.06 kg, both P < 0.001) added significantly to the prediction models. All three models validated in the athletes and patients with acromegaly but significantly (P < 0.01-0.001) over-predicted SM in the AN group as a whole. However, model 1 was validated in AN patients with BMIs in the model-development group range (n = 11; BMI of >16 kg/m(2)) but not in those with a BMI of <16 kg/m(2) (n = 12). The DXA-based models are accurate for predicting IMAT-free SM in selected populations and thus provide a new opportunity for quantifying SM in physiological and epidemiological investigations.     

Insulin resistance and serum concentrations of ovarian and adrenal androgen in obese women without additional disease and with policystic ovary syndrome

THE AIM: of the present study was to evaluate serum concentrations of adrenal and ovarian androgens and sex hormone-binding globulin in obese women without additional diseases and in obese women with polycystic ovary syndrome with and without insulin resistance. MATERIAL AND METHODS: The study group involved 73 obese women (39 with PCOS--A and 34 obese without additional diseases--B). The serum concentration of glucose and insulin were measured and the study group was divided on the basis of HOMA index into two subgroups: A I-PCO without insulin resistance (n=18, mean age 27.2+/-5.9 yr; BMI 33.2+/-3.5 kg/m2); AII-PCO with insulin resistance (n=21, mean age 27.5+/-7.1 yr; BMI 37.6+/-6.5 kg/m2); B I-obese without insulin resistance (n=8, age 33.5+/-7.5 yr; BMI 35.2+/-4.8 kg/m2); B II-obese with insulin resistance (n=24, age 30.3+/-5.2 yr; BMI 36.4+/-5.8 kg/m2). Body mass and height were measured and body mass index was calculated with formula. Body composition was measured using bioimpedance method. The serum concentrations of FSH, LH, total and free testosterone, androstendione, DHEAS, SHBG and insulin were determined by RIA method and glucose was determined by enzymatic procedure. RESULTS: We observed significantly higher body mass, fat mass and BMI in AII subgroup when compared to AI, BI and BII subgroups. Only serum concentration of free testosterone was significantly higher in AII subgroup when compared to AI subgroup. We observed a positive correlation between serum concentrations of insulin and free testosterone in both groups A and B, moreover we observed positive correlations between serum concentrations of insulin and both DHEAS and LH in group B. CONCLUSIONS: It seems that insulin resistance plays a key role in the development of hyperandrogenism in obese women. However mechanisms leading to hyperandrogenism in PCOS are still unrevealed and seem to be more complex.     

Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women

We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 +/- 1 kg/m(2)] and 10 upper body obese (UBO) women (BMI: 38 +/- 1 kg/m(2); waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 microgram. kg fat-free mass(-1). min(-1)) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (R(a)) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and (133)Xe clearance methods. Basal whole body FFA R(a) and glycerol R(a) were both greater (P < 0.05) in obese (449 +/- 31 and 220 +/- 12 micromol/min, respectively) compared with lean subjects (323 +/- 44 and 167 +/- 21 micromol/min, respectively). Epinephrine infusion significantly increased FFA R(a) and glycerol R(a) in lean (71 +/- 21 and 122 +/- 52%, respectively; P < 0.05) but not obese subjects (7 +/- 6 and 39 +/- 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.     

Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image.

A single abdominal cross-sectional computerized axial tomography and magnetic resonance image is often obtained in studies examining adipose tissue (AT) distribution. An abdominal image might also provide additional useful information on total body skeletal muscle (SM) and AT volumes with related physiological insights. We therefore investigated the relationships between abdominal SM and AT areas from single images and total body component volumes in a large and diverse sample of healthy adult subjects. Total body SM and AT volumes were derived by whole body multislice magnetic resonance imaging in 123 men [age (mean +/- SD) of 41.6 +/- 15.8 yr; body mass index of 25.9 +/- 3.4 kg/m(2)] and 205 women (age of 47.8 +/- 18.7 yr; body mass index of 26.7 +/- 5.6 kg/m(2)). Single abdominal SM and AT slice areas were highly correlated with total body SM (r = 0.71-0.92; r = 0.90 at L(4)-L(5) intervertebral space) and AT (r = 0.84-0.96; r = 0.94 at L(4)-L(5) intervertebral space) volumes, respectively. R(2) increased by only 5.7-6.1% for SM and 2.7-4.4% for AT with the inclusion of subject sex, age, ethnicity, scanning position, body mass index, and waist circumference in the model. The developed SM and AT models were validated in an additional 49 subjects. To achieve equivalent power to a study measuring total body SM or AT volumes, a study using a single abdominal image would require 17-24% more subjects for SM and 6-12% more subjects for AT. Measurement of a single abdominal image can thus provide estimates of total body SM and AT for group studies of healthy adults.     

Ethnic differences in in vitro glyceride synthesis in subcutaneous and omental adipose tissue

Considerable evidence suggests that there are ethnic differences in lipid metabolism between African American and Caucasian women, which may result in increased synthesis of fat in adipose tissue. The purpose of this study was to measure the in vitro rates of [14C]glucose incorporation into the glyceride-glycerol backbone of triglycerides (TG) and diglycerides (DG) in abdominal subcutaneous (SAT) and omental adipose tissue (OAT). Morbidly obese [African American (n = 15): body mass index (BMI) = 45 +/- 2.3; Caucasian (n = 18): BMI = 51 +/- 2.3] and preobese [African American (n = 7): BMI = 27 +/- 1.0; Caucasian (n = 7): BMI = 25 +/- 1.0] women were examined in this study. There were no significant differences in the rates of synthesis of either TG or DG in SAT of either preobese or obese women. On the other hand, both preobese and obese African American women had higher rates of synthesis of TG in OAT compared with their Caucasian counterparts. This increase in TG synthesis in OAT was not due to differences in cell size or rates of reesterification. Thus African American woman have an increased capacity to synthesize TG in OAT compared with Caucasian women, which may contribute to the higher prevalence of obesity in African American women.     

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 +/- 2 yr, BMI = 25.5 +/- 0.9 kg/m(2)) and low (IR; n = 18, 12 females and 6 males, age 45 +/- 2 yr, P = 0.49, BMI = 27.5 +/- 1.1 kg/m(2), P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU.min(-1).m(-2)) isoglycemic clamp tests. M(100-120 min) was higher in IS (10.7 +/- 0.7) than in IR (4.4 +/- 0.2 mg.min(-1).kg(-1), P < 10(-9)), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 +/- 6% vs. IS: 82 +/- 5%, P < 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24-28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 +/- 26 pg/ml vs. IS: 469 +/- 23 pg/ml, P < 0.02). Clamp insulin infusion reduced plasma obestatin to approximately 81% of basal values in IS (P < 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M (r = 0.34, P = 0.04), HDL cholesterol (r = 0.45, P = 0.01), and plasma ghrelin concentrations (r = 0.80, P < 0.000001) and negatively with measures of adiposity, plasma FFA during clamp (r = -0.42, P < 0.01), and systolic blood pressure (r = -0.33, P < 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.     

Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables

The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.     

Regional muscle and adipose tissue amino acid metabolism in lean and obese women

The effect of obesity on regional skeletal muscle and adipose tissue amino acid metabolism is not known. We evaluated systemic and regional (forearm and abdominal subcutaneous adipose tissue) amino acid metabolism, by use of a combination of stable isotope tracer and arteriovenous balance methods, in five lean women [body mass index (BMI) <25 kg/m(2)] and five women with abdominal obesity (BMI 35.0-39.9 kg/m(2); waist circumference >100 cm) who were matched on fat-free mass (FFM). All subjects were studied at 22 h of fasting to ensure that the subjects were in net protein breakdown during this early phase of starvation. Leucine rate of appearance in plasma (an index of whole body proteolysis), expressed per unit of FFM, was not significantly different between lean and obese groups (2.05 +/- 0.18 and 2.34 +/- 0.04 micromol x kg FFM(-1) x min(-1), respectively). However, the rate of leucine release from forearm and adipose tissues in obese women (24.0 +/- 4.8 and 16.6 +/- 6.5 nmol x 100 g(-1) x min(-1), respectively) was lower than in lean women (66.8 +/- 10.6 and 38.6 +/- 7.0 nmol x 100 g(-1) x min(-1), respectively; P < 0.05). Approximately 5-10% of total whole body leucine release into plasma was derived from adipose tissue in lean and obese women. The results of this study demonstrate that the rate of release of amino acids per unit of forearm and adipose tissue at 22 h of fasting is lower in women with abdominal obesity than in lean women, which may help obese women decrease body protein losses during fasting. In addition, adipose tissue is a quantitatively important site for proteolysis in both lean and obese subjects.     

Determining the waist circumference in african americans which best predicts insulin resistance

Total body size and central fat distribution are important determinants of insulin resistance. The BMI and waist circumference (WC) thresholds in African Americans that best predict insulin resistance are unknown. Our goal was to determine the BMI and WC values in African Americans, which optimally predict insulin resistance. The subjects were African Americans (68 men, 63 women), aged 35 +/- 8 years (mean +/- s.d.), with a BMI of 30.9 +/- 7.5, in the range of 18.5-54.7 kg/m(2), and with a WC of 98 +/- 18, in the range of 69-173 cm. Insulin resistance was defined by the lowest tertile of the insulin sensitivity index (S(I)). The Youden index was calculated to determine the WC and BMI thresholds that predict insulin resistance with an optimal combination of sensitivity and specificity. In men the thresholds that optimally predicted insulin resistance were a BMI > or =30 kg/m(2) or a WC > or =102 cm. For women, insulin resistance was best predicted by a BMI > or =32 kg/m(2) or a WC > or =98 cm. In African Americans, insulin resistance (in men) was best predicted by a WC > or =102 cm, and in women by a WC > or =98 cm, or by a BMI value that fell in the obese category (men: > or =30 kg/m(2), women: > or =32 kg/m(2)).     

Pedometer-determined physical activity and indicators of health in Japanese adults

Recently, many cross-sectional studies observed that body mass index (BMI) and percentage of body fat (%BF) were inversely associated with pedometer-determined physical activities, but studies on Asian populations, including the Japanese, are sparse. Height, weight, body fat percentage (%BF, bioelectrical impedance analyzer), and waist circumference were measured on 117 women (62.8+/-4.5 years, 22.2+/-2.2 kg/m(2)) and 62 men (64.0+/-4.6 years, 23.6+/-2.5 kg/m(2)). Pearson correlations and partial correlation coefficients after controlling for age were calculated between steps/day and variables. Furthermore, participants were classified into four groups as follows: <5,000, 5,000-7,499, 7,500-9,999, and >or=10,000 steps/day, and analyzed using ANOVA across activity groups. In women, a significant correlation was found between steps/day and BMI (r=-0.217, p=0.018), %BF (r=-0.292, p=0.0014), and the relationship was still significant after controlling for age. The relationship between steps/day and waist circumference was not significant. In men, a significant relationship was not observed between steps/day and obesity indices. The correlations between steps/day and both BMI and %BF were significant in Japanese women, but weak compared with Caucasian and African-American women as reported previously. A possible cause is racial difference in degree of obesity and body shape. The effects of physical activity on body shape and composition may differ according to race.     

Fatty acid oxidation in African-American and Caucasian women during physical activity.

The goal of this study was to determine whether differences in physical activity-related fat oxidation exist between lean and obese African-American (LAA and OAA) and lean and obese Caucasian (LC and OC) premenopausal women. Lean AA (28.4 +/- 2.8 yr, n = 7), LC (24.7 +/- 1.8 yr, n = 9), OAA (30.9 +/- 2.2 yr, n = 11), and OC (34.1 +/- 2.5 yr, n = 9) women underwent preliminary assessment of peak aerobic capacity (VO2 peak). On a subsequent testing day, participants exercised after an 8-h fast on a cycle ergometer at 15 W (approximately 40% VO2 peak) for 10 min and then for 10 min at approximately 65% VO2 peak). Fatty acid oxidation was determined using the average respiratory exchange ratio and O2 consumption during minutes 5-9 of the exercise session. Percent body fat and fat-free mass were lower (P < 0.05) in LAA (25.8 +/- 2.8% and 48.3 kg) and LC (26.4 +/- 2.0% and 45.8 +/- 1.7 kg) than in OAA (41.2 +/- 1.3% and 58.8 +/- 3.3 kg) and OC (39.3 +/- 2.7% and 58.6 kg) women. Fat oxidation among the groups was analyzed statistically using analysis of covariance with fat-free mass and VO2 peak) as covariates. During exercise at 15 W, fat oxidation was as low in LAA (0.134 +/- 0.024 g/min) as in OAA (0.144 +/- 0.026 g/min) and OC (0.156 +/- 0.020 g/min) women: all these rates of fat oxidation were lower than in LC women (0.200 +/- 0.021 g/min, P < 0.05, LC vs. all other groups). Fatty acid oxidation during higher-intensity exercise (65% VO2 peak)) was higher in LC than in OC women but was not statistically different between African-American and Caucasian groups. Fatty acid oxidation was therefore lower during low-intensity physical activity in OAA, LAA, and OC than in LC women.     

Body mass index, free insulin-like growth factor I, and physical function among older adults: results from the ilSIRENTE study

The aim of the present study was to evaluate the mediating role played by obesity on the relationship of free insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) with muscle strength and physical performance. Data were from baseline evaluation of the ilSIRENTE Study. Muscle strength was measured by hand grip strength. Physical performance was assessed using the walking speed and the 0-3 Short Physical Performance Battery (SPPB) score. Based on its median value, free IGF-I was categorized in the following two groups: low IGF-I (IGF-I <0.65 ng/ml; n = 174) and high IGF-I (IGF-I > or =0.65 ng/ml; n = 175). Similarly, IGFBP-3 was categorized in the following two groups: low IGFBP-3 (IGFBP-3 <4,319.9 ng/ml; n = 174) and high IGFBP-3 (IGFBP-3 > or =4,319.9 ng/ml; n = 175). Body mass index (BMI) was categorized as follows: <25 kg/m(2) (n = 160), 25-29.9 kg/m(2) (n = 133), > or =30 kg/m(2) (n = 56). Mean age of the 349 participants was 85.8 yr, and 234 (67%) were women. After adjusting for potential confounders, no significant association of IGF-I and IGFBP-3 with study outcomes was observed. After the study sample was stratified by BMI groups, compared with participants with low IGF-I level, those with high IGF-I level had a significantly better grip strength [35.2 +/- 1.6 vs. 29.2 +/- 2.0 (SE) kg, P = 0.03], walking speed (0.55 +/- 0.04 vs. 0.40 +/- 0.04 m/s, P = 0.01), and SPPB score (1.9 +/- 0.1 vs. 1.5 +/- 0.1 m/s, P = 0.01) but only in the group with BMI > or =30 kg/m(2) and not in other BMI groups. A statistically significant interaction between BMI and IGF-I level was observed on all study outcomes. By contrast, no association was observed between IGFBP-3 and study outcomes, independently of BMI. In conclusion, high IGF-I level is associated with better physical function in older persons with obesity, but not in nonobese subjects.     

Impaired plasma fatty acid oxidation in extremely obese women

Skeletal muscle from extremely obese individuals exhibits decreased lipid oxidation compared with muscle from lean controls. It is unknown whether this effect is observed in vivo or whether the phenotype is preserved after massive weight loss. The objective of this study was to compare free fatty acid (FFA) oxidation during rest and exercise in female subjects who were either lean [n = 7; body mass index (BMI) = 22.6 +/- 2.2 kg/m(2)] or extremely obese (n = 10; BMI = 40.8 +/- 5.4 kg/m(2)) or postgastric bypass patients who had lost >45 kg (weight reduced) (n = 6; BMI = 33.7 +/- 9.9 kg/m(2)) with the use of tracer ([(13)C]palmitate and [(14)C]acetate) methodology and indirect calorimetry. The lean group oxidized significantly more plasma FFA, as measured by percent fatty acid uptake oxidized, than the extremely obese or weight-reduced group during rest (66.6 +/- 14.9 vs. 41.5 +/- 16.4 vs. 39.9 +/- 15.3%) and exercise (86.3 +/- 11.9 vs. 56.3 +/- 22.1 vs. 57.3 +/- 20.3%, respectively). BMI significantly correlated with percent uptake oxidized during both rest (r = -0.455) and exercise (r = -0.459). In conclusion, extremely obese women and weight-reduced women both possess inherent defects in plasma FFA oxidation, which may play a role in massive weight gain and associated comorbidities.     

Adipose tissue distribution in relation to insulin resistance in type 2 diabetes mellitus

Insulin resistance (IR) is typically more severe in obese individuals with type 2 diabetes (T2DM) than in similarly obese non-diabetics but whether there are group differences in body composition and whether such differences contribute to the more severe IR of T2DM is uncertain. DEXA and regional CT imaging were conducted to assess adipose tissue (AT) distribution and fat content in liver and muscle in 67 participants with T2DM (F39/M28, age 60 +/- 7 yr, BMI 34 +/- 3 kg/m(2)) and in 35 similarly obese, non-DM volunteers (F20/M15, age 55 +/- 8 yr, BMI 33 +/- 2 kg/m(2)). A biopsy of subcutaneous abdominal AT was done to measure adipocyte size. A glucose clamp was performed at an insulin infusion of 80 mU x min(-1) x m(-2). There was more severe IR in T2DM (6.1 +/- 2.3 vs. 9.9 +/- 3.3 mg x min(-1) x kg FFM(-1); P < 0.01). Group comparisons of body composition parameters was performed after adjusting for the effect of age, gender, race, height and total fat mass (FM). T2DM was associated with less leg FM (-1.2 +/- 0.4 kg, P < 0.01), more trunk FM (+1.1 +/- 0.4 kg, P < 0.05), greater hepatic fat (P < 0.05), and more subfascial adipose tissue around skeletal muscle (P < 0.05). There was a significant group x sex interaction for VAT (P < 0.01), with greater VAT in women with T2DM (P < 0.01). Mean adipocyte size (AS) did not significantly differ across groups, and smaller AS was associated with increased leg FM, whereas larger AS was related to more trunk FM (both P < 0.05). Group differences in IR were less after adjusting for group differences in leg FM, trunk FM, and hepatic fat, but these adjustments only partially accounted for the greater severity of IR in T2DM. In summary, T2DM, compared with similarly obese nondiabetic men and women, is associated with less leg FM and greater trunk FM and hepatic fat.     

Leptin production during early starvation in lean and obese women

We evaluated abdominal adipose tissue leptin production during short-term fasting in nine lean [body mass index (BMI) 21 +/- 1 kg/m(2)] and nine upper body obese (BMI 36 +/- 1 kg/m(2)) women. Leptin kinetics were determined by arteriovenous balance across abdominal subcutaneous adipose tissue at 14 and 22 h of fasting. At 14 h of fasting, net leptin release from abdominal adipose tissue in obese subjects (10.9 +/- 1.9 ng x 100 g tissue x (-1) x min(-1)) was not significantly greater than the values observed in the lean group (7.6 +/- 2.1 ng x 100 g(-1) x min(-1)). Estimated whole body leptin production was approximately fivefold greater in obese (6.97 +/- 1.18 microg/min) than lean subjects (1.25 +/- 0.28 microg/min) (P < 0.005). At 22 h of fasting, leptin production rates decreased in both lean and obese groups (to 3.10 +/- 1.31 and 10.5 +/- 2.3 ng x 100 g adipose tissue(-1) x min(-1), respectively). However, the relative declines in both arterial leptin concentration and local leptin production in obese women (arterial concentration 13.8 +/- 4.4%, local production 10.0 +/- 12.3%) were less (P < 0.05 for both) than the relative decline in lean women (arterial concentration 39.0 +/- 5.5%, local production 56.9 +/- 13.0%). This study demonstrates that decreased leptin production accounts for the decline in plasma leptin concentration observed after fasting. However, compared with lean women, the fasting-induced decline in leptin production is blunted in women with upper body obesity. Differences in leptin production during fasting may be responsible for differences in the neuroendocrine response to fasting previously observed in lean and obese women.     

Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/- 0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin (r = -0.46, P < 0.05) and tended to be negatively related to adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/- 0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.     

The Q121/Q121 genotype of ENPP1/PC-1 is associated with lower BMI in non-diabetic whites

This study investigated the role of the ENPP1/PC-1 gene K121Q polymorphism in predicting BMI (kg/m2) in non-diabetic individuals. Three independent samples (n = 631, n = 304, and n = 505) of adult whites were analyzed. Selection criteria were fasting plasma glucose level <126 mg/dL, absence of severe obesity (BMI > or =40 kg/m2), and lack of treatment known to modulate BMI. In Sample 1, BMI values were different in individuals carrying the K121/K121 (KK), K121/Q121 (KQ), and Q121/Q121 (QQ) genotypes (25.5 +/- 4.3, 25.3 +/- 4.1, and 22.8 +/- 2.5 kg/m2, respectively (adjusted p = 0.022); BMI values in Samples 2 and 3 also tended to be different, although the differences, after adjustment for age and sex, did not reach statistical significance. When data were pooled, BMI values were 25.8 +/- 4.4, 25.6 +/- 4.4, and 23.6 +/- 3.3 kg/m2 in KK, KQ, and QQ individuals (adjusted p = 0.029). According to a recessive model, QQ individuals had lower BMI values than KK and KQ individuals combined (23.6 +/- 3.3 kg/m2 vs. 25.7 +/- 4.4 kg/m2; adjusted p = 0.008). These data suggest that the QQ genotype of the ENPP1/PC-1 gene is associated with lower BMI. If similar results are confirmed in prospective studies, the K121Q polymorphism may help identify people at risk for obesity.     

Fasting for 72 h increases intramyocellular lipid content in nondiabetic,physically fit men

The purpose of this study was to determine changes in intramyocellular lipid (IMCL) content in the vastus lateralis of nondiabetic, physically fit males over 72 h of fasting. Six men, mean age 35 yr (range 23-55 yr), body mass index 23.7 kg/m2 (21.2-27.4 kg/m2), undertook a water-only fast for 84 h. Vastus lateralis IMCL content was determined using proton magnetic resonance spectroscopy after 12 and 84 h of fasting. Venous blood was sampled at 12-h intervals throughout the fast. IMCL-(CH2)n/water and IMCL-(CH2)n/total creatine ratios increased from 0.00623 +/- 0.00065 to 0.0142 +/- 0.0015 (P = 0.002) and 6.82 +/- 0.87 to 14.96 +/- 1.73 (P = 0.001), respectively. Plasma free fatty acid (FFA), serum triglyceride, and whole blood 3-hydroxybutyrate concentrations increased (P < 0.001, <0.05, <0.03, respectively), whereas plasma glucose and serum insulin concentrations decreased (both P < 0.001) during fasting. In conclusion, 72-h water-only fasting produces a large increase in plasma FFA concentration, a drop in serum insulin concentration, and accumulation of IMCL in the vastus lateralis muscle of nondiabetic, physically fit men.