Adipose tissue interleukin-18 mRNA and plasma interleukin-18: effect of obesity and exercise

Objectives: Obesity and a physically inactive lifestyle are associated with increased risk of developing insulin resistance. The hypothesis that obesity is associated with increased adipose tissue (AT) interleukin (IL)‐18 mRNA expression and that AT IL‐18 mRNA expression is related to insulin resistance was tested. Furthermore, we speculated that acute exercise and exercise training would regulate AT IL‐18 mRNA expression. Research Methods and Procedures: Non‐obese subjects with BMI < 30 kg/m² (women: n = 18; men; n = 11) and obese subjects with BMI >30 kg/m² (women: n = 6; men: n = 7) participated in the study. Blood samples and abdominal subcutaneous AT biopsies were obtained at rest, immediately after an acute exercise bout, and at 2 hours or 10 hours of recovery. After 8 weeks of exercise training of the obese group, sampling was repeated 48 hours after the last training session. Results: AT IL‐18 mRNA content and plasma IL‐18 concentration were higher (p < 0.05) in the obese group than in the non‐obese group. AT IL‐18 mRNA content and plasma IL‐18 concentration was positively correlated (p < 0.05) with insulin resistance. While acute exercise did not affect IL‐18 mRNA expression at the studied time‐points, exercise training reduced AT IL‐18 mRNA content by 20% in both sexes. Discussion: Because obesity and insulin resistance were associated with elevated AT IL‐18 mRNA and plasma IL‐18 levels, the training‐induced lowering of AT IL‐18 mRNA content may contribute to the beneficial effects of regular physical activity with improved insulin sensitivity.     

Regular Multicomponent Exercise Increases Physical Fitness and Muscle Protein Anabolism in Frail,Obese, Older Adults

Aging is associated with a decline in strength, endurance, balance, and mobility. Obesity worsens the age‐related impairment in physical function and often leads to frailty. The American College of Sports Medicine recommends a multicomponent (strength, endurance, flexibility, and balance) exercise program to maintain physical fitness. However, the effect of such an exercise program on physical fitness in frail, obese older adults is not known. We therefore determined the effect of a 3‐month long multicomponent exercise training program, on endurance (peak aerobic capacity (VO₂ peak)), muscle strength, muscle mass, and the rate of muscle protein synthesis (basal rate and anabolic response to feeding) in nine 65‐ to 80‐year‐old, moderately frail, obese older adults. After 3 months of training, fat mass decreased (P < 0.05) whereas fat‐free mass (FFM), appendicular lean body mass, strength, and VO₂ peak increased (all P < 0.05). Regular strength and endurance exercise increased the mixed muscle protein fractional synthesis rate (FSR) but had no effect on the feeding‐induced increase in muscle protein FSR (～0.02%/h increase from basal values both before and after exercise training; effect of feeding: P = 0.02; effect of training: P = 0.047; no interaction: P = 0.84). We conclude that: (i) a multicomponent exercise training program has beneficial effects on muscle mass and physical function and should therefore be recommended to frail, obese older adults, and (ii) regular multicomponent exercise increases the basal rate of muscle protein synthesis without affecting the magnitude of the muscle protein anabolic response to feeding.     

Resistance Training Improves Cardiovascular Risk Factors in Obese Women Despite a Significative Decrease in Serum Adiponectin Levels

Increased circulating adiponectin and insulin sensitivity are usually observed after body fat loss induced by a weight‐loss diet. Progressive resistance training (PRT) without a concomitant weight‐loss diet significantly decreases visceral fat, thus improving insulin sensitivity. Therefore, the purpose of this study was to ascertain the effects of combined 16‐week PRT and weight‐loss diet on circulating adiponectin and insulin sensitivity index. Thirty‐four obese (BMI: 30–40 kg/m²) women, aged 40–60 year, were randomized to three groups: a control group (C; n = 9); a diet group (WL; n = 12) with a caloric restriction of 500 kcal/d; and a diet plus resistance training group (WL+RT; n = 13) with the same caloric restriction as group WL and a 16‐week supervised whole body PRT of two sessions/week. Both WL and WL+RT groups showed similar decreases in body mass (?6.3% and ?7.7%) and visceral fat (?19.9% and ?20.5%). WL resulted in an expected increase in circulating levels of adiponectin (P = 0.07) and insulin sensitivity. However, circulating total adiponectin decreased (P < 0.05) in WL+RT group, whereas an improvement in different cardiovascular risk factors (insulin sensitivity, low‐density lipoprotein cholesterol (LDL‐C), etc.) was observed. In conclusion, in obese women a 16‐week combined PRT and weight‐loss diet is accompanied by significant improvements in different cardiovascular risk factors in spite of a significant decrease of circulating adiponectin.     

Severe Obesity Is Associated With Impaired Arterial Smooth Muscle Function in Young Adults

The degree of arterial dilatation induced by exogenous nitrates (nitrate‐mediated dilatation, NMD) has been similar in obese and normal‐weight adults after single high‐dose glyceryl trinitrate (GTN). We examined whether NMD is impaired in obesity by performing a GTN dose‐response study, as this is a potentially more sensitive measure of arterial smooth muscle function. In this cross‐sectional study, subjects were 19 obese (age 31.0 ± 1.2 years, 10 male, BMI 44.1 ± 2.1) and 19 age‐ and sex‐matched normal‐weight (BMI 22.4 ± 0.4) young adults. Blood pressure (BP), triglycerides, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL)‐cholesterol, glucose, insulin, high‐sensitivity C‐reactive protein (hs‐CRP), carotid intima‐media thickness (CIMT), and flow‐mediated dilatation (FMD) were measured. After incremental doses of GTN, brachial artery maximal percent dilatation (maximal NMD) and the area under the dose‐response curve (NMD AUC) were calculated. Maximal NMD (13.4 ± 0.9% vs. 18.3 ± 1.1%, P = 0.002) and NMD AUC (54,316 ± 362 vs. 55,613 ± 375, P = 0.018) were lower in obese subjects. The obese had significantly higher hs‐CRP, insulin, and CIMT and lower HDL‐cholesterol. Significant bivariate associations existed between maximal NMD or NMD AUC and BMI‐group (r = ?0.492, P = 0.001 or r = ?0.383, P = 0.009), hs‐CRP (r = ?0.419, P = 0.004 or r = ?0.351, P = 0.015), and HDL‐cholesterol (r = 0.374, P = 0.01 or r = 0.270, P = 0.05). On multivariate analysis, higher BMI‐group remained as the only significant determinant of maximal NMD (r² = 0.242, β = ?0.492, P = 0.002) and NMD AUC (r² = 0.147, β = ?0.383, P = 0.023). In conclusion, arterial smooth muscle function is significantly impaired in the obese. This may be important in their increased cardiovascular risk.     

Effects of Exercise on Metabolic Risk Variables in Overweight Postmenopausal Women: A Randomized Clinical Trial

Objective: This study examined the effects of exercise on metabolic risk variables insulin, leptin, glucose, and triglycerides in overweight/obese postmenopausal women. Research Methods and Procedures: Sedentary women (n = 173) who were overweight or obese (BMI ≥ 25 kg/m² or ≥24 kg/m² with ≥33% body fat), 50 to 75 years of age, were randomized to 12 months of exercise (≥45 minutes of moderate‐intensity aerobic activity 5 d/wk) or to a stretching control group. Body composition (DXA) and visceral adiposity (computed tomography) were measured at baseline and 12 months. Insulin, glucose, triglycerides, and leptin were measured at baseline and 3 and 12 months. Insulin resistance was evaluated by the homeostasis model assessment formula. Differences from baseline to follow‐up were calculated and compared across groups. Results: Exercisers had a 4% decrease and controls had a 12% increase in insulin concentrations from baseline to 12 months (p = 0.0002). Over the same 12‐month period, leptin concentrations decreased by 7% among exercisers compared with remaining constant among controls (p = 0.03). Homeostasis model assessment scores decreased by 2% among exercisers and increased 14% among controls from baseline to 12 months (p = 0.0005). The exercise effect on insulin was modified by changes in total fat mass (trend, p = 0.03), such that the exercise intervention abolished increases in insulin concentrations associated with gains in total fat mass. Discussion: Regular moderate‐intensity exercise can be used to improve metabolic risk variables such as insulin and leptin in overweight/obese postmenopausal women. These results are promising for health care providers providing advice to postmenopausal women for lifestyle changes to reduce risk of insulin resistance, coronary heart disease, and diabetes.     

Resistance training lowers exercise-induced oxidative stress and homocysteine levels in overweight and obese older adults

Objective: To compare exercise‐induced oxidative stress and levels of homocysteine and cholesterol in normal‐weight and overweight older adults after resistance exercise (RX). Research Methods and Procedures: This interventional study was conducted at a wellness center. Forty‐nine older adults (age range, 60 to 72 years) were stratified by BMI (<25 kg/m² normal weight, ≥25 kg/m² overweight/obese) and then randomly assigned to either a control non‐exercise group or an RX group. The RX group completed a 6‐month training program. Exercise‐induced lipid hydroperoxides (PEROXs) and thiobarbituric‐reactive acid substances, homocysteine, lipoprotein a, cholesterol, and high‐density lipoprotein cholesterol were measured before and after the 6‐month RX program. Results: PEROXs and thiobarbituric‐reactive acid substances were lower in both the overweight/obese and normal‐weight RX‐trained groups compared with control groups (p < 0.05). Homocysteine levels were lower in both overweight/obese and normal‐weight RX groups compared with control groups (p < 0.05). Lipoprotein a, total cholesterol, and high‐density lipoprotein cholesterol were not different in normal‐weight and overweight/obese groups before or after RX. The change in muscle strength was correlated with homocysteine at 6 months (r = ?0.452, p < 0.05), whereas the change in PEROXs was correlated with the change in body fat (r = ?0.329). Discussion: To our knowledge, these data are the first to show that RX reduces exercise‐induced oxidative stress and homocysteine regardless of adiposity, indicating that this protection can be afforded in an older, overweight/obese population as effectively as in healthy older adults. These data suggest that RX may afford some protection against emerging cardiovascular risk factors using a mode of exercise that supports body weight.     

Fat Depot‐specific Impact of Visceral Obesity on Adipocyte Adiponectin Release in Women

Our objective was to examine omental and subcutaneous adipocyte adiponectin release in women. We tested the hypothesis that adiponectin release would be reduced to a greater extent in omental than in subcutaneous adipocytes of women with visceral obesity. Omental and subcutaneous adipose tissue samples were obtained from 52 women undergoing abdominal hysterectomies (age: 47.1 ± 4.8 years; BMI: 26.7 ± 4.7 kg/m²). Adipocytes were isolated and their adiponectin release in the medium was measured over 2 h. Measures of body fat accumulation and distribution were obtained using dual‐energy X‐ray absorptiometry and computed tomography, respectively. Adiponectin release by omental and subcutaneous adipocytes was similar in lean individuals; however, in subsamples of obese or visceral obese women, adiponectin release by omental adipocytes was significantly reduced while that of subcutaneous adipocytes was not affected. Omental adipocyte adiponectin release was significantly and negatively correlated with total body fat mass (r = ?0.47, P < 0.01), visceral adipose tissue area (r = ?0.50, P < 0.01), omental adipocyte diameter (r = ?0.43, P < 0.01), triglyceride levels (r = ?0.32, P ≤ 0.05), cholesterol/high‐density lipoprotein (HDL)‐cholesterol (r = ?0.31, P ≤ 0.05), fasting glucose (r = ?0.39, P ≤ 0.01), fasting insulin (r = ?0.36, P ≤ 0.05), homeostasis model assessment index (r = ?0.39, P ≤ 0.01), and positively associated with HDL‐cholesterol concentrations (r = 0.33, P ≤ 0.05). Adiponectin release from subcutaneous cells was not associated with any measure of adiposity, lipid profile, or glucose homeostasis. In conclusion, compared to subcutaneous adipocyte adiponectin release, omental adipocyte adiponectin release is reduced to a greater extent in visceral obese women and better predicts obesity‐associated metabolic abnormalities.     

The Macrophage‐Specific Serum Marker,Soluble CD163, Is Increased in Obesity and Reduced After Dietary‐Induced Weight Loss

Objective: Soluble CD163 (sCD163) is a new macrophage‐specific serum marker elevated in inflammatory conditions. sCD163 is elevated in obesity and found to be a strong predictor of the development of type 2 diabetes. We investigated whether dietary intervention and moderate exercise was related to changes in sCD163 and how sCD163 is associated to insulin resistance in obesity. Design and Methods: Ninety‐six obese subjects were enrolled: 62 followed a very low energy diet (VLED) program for 8 weeks followed by 3‐4 weeks of weight stabilization, 20 followed a moderate exercise program for 12 weeks, and 14 were included without any intervention. Fasting blood samples and anthropometric measures were taken at baseline and after intervention. Thirty‐six lean subjects were included in a control group. Results: sCD163 was significantly higher in obese subjects (2.3 ± 1.0 mg/l) compared with lean (1.6 ± 0.4 mg/l, P < 0.001). Weight loss (11%) induced by VLED resulted in a reduction and partial normalization of sCD163 to 2.0 ± 0.9 mg/l (P < 0.001). Exercise for 12 weeks had no effect on sCD163. At baseline, sCD163 was significantly correlated with BMI (r = 0.46), waist circumference (r = 0.40), insulin resistance measured by the homeostasis model assessment (HOMA‐IR; r = 0.41; all P < 0.001), and the leptin‐to‐adiponectin ratio (r = 0.28, P < 0.05). In a multivariate linear regression analysis with various inflammatory markers, sCD163 (β = 0.25), adiponectin (β = ?0.24), and high sensitivity C‐reactive protein (hs‐CRP; β = 0.20) remained independently and significantly associated to HOMA‐IR (all P < 0.05). After further adjustment for waist circumference, only sCD163 was associated with HOMA‐IR (P < 0.05). Conclusion: The macrophage‐specific serum marker sCD163 is increased in obesity and partially normalized by dietary‐induced weight loss but not by moderate exercise. Furthermore, we confirm that sCD163 is a good marker for obesity‐related insulin resistance.     

Racial Differences in Adipocyte Size and Relationship to the Metabolic Syndrome in Obese Women

Objective: To determine whether racial differences exist in the relationship of the abnormalities defining the metabolic syndrome (MS) to regional adiposity and fat cell size (FCS) in obese postmenopausal women. Research Methods and Procedures: We determined the relationship of metabolic variables associated with the MS to regional body composition and abdominal (ABD) and gluteal (GLT) FCS in 25 white (CAU) and 25 African‐American (AF‐AMER) older women matched for age (58 ± 5 years; mean ± SD) and BMI (35 ± 4 kg/m²). Results: MS was present in 36% of the AF‐AMER and 57% of the CAU women. There were no differences in total body, trunk, gluteofemoral fat mass or regional FCS, but AF‐AMER women had 22% lower visceral fat, 24% higher insulin, and 31% lower triglyceride levels than CAU women (p < 0.05). Multiple regression analysis with body fat, visceral ABD fat area, and FCS as independent variables showed that GLT FCS was independently correlated with 2‐hour insulin (r = 0.56), triglyceride (r = 0.62), and high‐density lipoprotein cholesterol (r = ?0.72) levels in AF‐AMER women but not in CAU women, where only systolic blood pressure correlated with subcutaneous ABD fat area (r = 0.57) (p < 0.05). Discussion: The associations between GLT FCS and metabolic dysfunction in obese AF‐AMER but not CAU women suggest that central obesity is a less valid predictor of the MS in obese postmenopausal AF‐AMER women than in CAU women and that GLT FCS may be a more sensitive indicator of risk for the MS in AF‐AMER women.     

Ethnic Differences in Visceral Adipose Tissue and Type 2 Diabetes: Filipino,African‐American,and White Women

Objective: To compare ethnic differences in visceral adipose tissue (VAT), assessed by computed tomography, and type 2 diabetes risk among 55‐ to 80‐year‐old Filipino, African‐American, and white women without known cardiovascular disease. Research Methods and Procedures: Subjects were participants in the Rancho Bernardo Study (n = 196), the Filipino Women's Health Study (n = 181), and the Health Assessment Study of African‐American Women (n = 193). Glucose and anthropometric measurements were assessed between 1995 and 2002. Results: African‐American women had significantly higher age‐adjusted BMI (29.7 kg/m²) and waist girth (88.1 cm) compared with Filipino (BMI, 25.5 kg/m²; waist girth, 81.9 cm) or white (BMI: 26.0 kg/m²; waist girth: 80.7 cm) women. However, VAT was significantly higher among Filipino (69.1 cm³) compared with white (62.3 cm³; p = 0.037) or African‐American (57.5 cm³, p < 0.001) women. VAT correlated better with BMI (r = 0.69) and waist (r = 0.77) in whites, compared with Filipino (r = 0.42; r = 0.59) or African‐American (r = 0.50; r = 0.56) women. Age‐adjusted type 2 diabetes prevalence was significantly higher in Filipinas (32.1%) than in white (5.8%) or African‐American (12.1%) women. Filipinas had higher type 2 diabetes risk compared with African Americans [adjusted odds ratio, 2.30; 95% confidence interval (CI), 1.09 to 4.86] or whites (adjusted odds ratio, 7.51; 95% CI, 2.51 to 22.5) after adjusting for age, VAT, exercise, education, and alcohol intake. Discussion: VAT was highest among Filipinas despite similar BMI and waist circumference as whites. BMI and waist circumference were weaker estimates of VAT in Filipino and African‐American women than in whites. Type 2 diabetes prevalence was highest among Filipino women at every level of VAT, but VAT did not explain their elevated type 2 diabetes risk.     

Influence of Visceral Obesity and Liver Fat on Vascular Structure and Function in Obese Subjects

Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = ?0.577, P < 0.0001 and r = ?0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r² = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r² = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.     

The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss

Age‐related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ‐agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m²) and women (n = 40, BMI = 33.3 ± 4.9 kg/m²) during weight loss. All participants underwent a 16‐week hypocaloric weight‐loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow‐up using computed tomography (CT). Lean mass was measured using dual X‐ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (?1,160 vs. ?647 cm³, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (?104 vs. ?298 cm³, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: ?43 vs. ?88 cm³, P = 0.005; women: ?34 vs. ?59 cm³, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.     

Adipocytes IGFBP‐2 Expression in Prepubertal Obese Children

Aims of the study were to measure insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP‐2 expression, circulating IGFBP‐2, obesity, and insulin sensitivity in obese children. Thirty‐eight obese children were recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test and body composition by total‐body dual‐energy X‐ray absorptiometry. Serum free and total IGF‐I, IGFBP‐2, adiponectin, and leptin were measured. Relative quantification of IGFBP‐2 mRNA by subcutaneous adipose tissue biopsies was obtained using real‐time PCR. Circulating IGFBP‐2 was positively associated with insulin sensitivity, in agreement with previous studies. IGFBP‐2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = ?0.604; P < 0.05), free IGF‐I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP‐2 (r = 0.003, P = ns). The association between IGFBP‐2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate). In conclusion, circulating IGFBP‐2 was positively associated with insulin sensitivity. IGFBP‐2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity. IGFBP‐2 expression may potentially be one of the local mechanisms used by adipocytes to limit further fat gain.     

Improved insulin sensitivity and adiponectin level after exercise training in obese Korean youth

Objective: The objective of this study was to investigate the association among adiposity, insulin resistance, and inflammatory markers [high‐sensitivity C‐reactive protein (hs‐CRP), interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α] and adiponectin and to study the effects of exercise training on adiposity, insulin resistance, and inflammatory markers among obese male Korean adolescents. Research Methods and Procedures: Twenty‐six obese and 14 lean age‐matched male adolescents were studied. We divided the obese subjects into two groups: obese exercise group (N = 14) and obese control group (N = 12). The obese exercise group underwent 6 weeks of jump rope exercise training (40 min/d, 5 d/wk). Adiposity, insulin resistance, lipid profile, hs‐CRP, IL‐6, TNF‐α, and adiponectin were measured before and after the completion of exercise training. Results: The current study demonstrated higher insulin resistance, total cholesterol, LDL‐C levels, triglyceride, and inflammatory markers and lower adiponectin and HDL‐C in obese Korean male adolescents. Six weeks of increased physical activity improved body composition, insulin sensitivity, and adiponectin levels in obese Korean male adolescents without changes in TNF‐α, IL‐6, and hs‐CRP. Discussion: Obese Korean male adolescents showed reduced adiponectin levels and increased inflammatory cytokines. Six weeks of jump rope exercise improved triglyceride and insulin sensitivity and increased adiponectin levels.     

A 12‐Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese,Hispanic Adolescents

The rise in obesity‐related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized that a 12‐week controlled aerobic exercise program without weight loss reduces visceral, hepatic, and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents. Twenty‐nine postpubertal (Tanner stage IV and V), Hispanic adolescents, 15 obese (7 boys, 8 girls; 15.6 ± 0.4 years; 33.7 ± 1.1 kg/m²; 38.3 ± 1.5% body fat) and 14 lean (10 boys, 4 girls; 15.1 ± 0.3 years; 20.6 ± 0.8 kg/m²; 18.9 ± 1.5% body fat), completed a 12‐week aerobic exercise program (4 × 30 min/week at ≥70% of peak oxygen consumption (VO₂peak)). Measurements of cardiovascular fitness, visceral, hepatic, and intramyocellular fat content (magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS)), and insulin resistance were obtained at baseline and postexercise. In both groups, fitness increased (obese: 13 ± 2%, lean: 16 ± 4%; both P < 0.01). In obese participants, intramyocellular fat remained unchanged, whereas hepatic fat content decreased from 8.9 ± 3.2 to 5.6 ± 1.8%; P < 0.05 and visceral fat content from 54.7 ± 6.0 to 49.6 ± 5.5 cm²; P < 0.05. Insulin resistance decreased indicated by decreased fasting insulin (21.8 ± 2.7 to 18.2 ± 2.4 µU/ml; P < 0.01) and homeostasis model assessment of insulin resistance (HOMA_IR) (4.9 ± 0.7 to 4.1 ± 0.6; P < 0.01). The decrease in visceral fat correlated with the decrease in fasting insulin (R² = 0.40; P < 0.05). No significant changes were observed in any parameter in lean participants except a small increase in lean body mass (LBM). Thus, a controlled aerobic exercise program, without weight loss, reduced hepatic and visceral fat accumulation, and decreased insulin resistance in obese adolescents.     

Association Between the 4 bp Proinsulin Gene Insertion Polymorphism (IVS‐69) and Body Composition in Black South African Women

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS‐69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS‐69 genotype were measured in 115 normal‐weight (BMI <25 kg/m²) and 138 obese (BMI ≥30 kg/m²) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI ≥35kg/m²) compared with the normal‐weight group (P = 0.029). Obese subjects with the insertion allele had greater fat mass (42.3 ± 0.9 vs. 38.9 ± 0.9 kg, P = 0.034) and fat‐free soft tissue mass (47.4 ± 0.6 vs. 45.1 ± 0.6 kg, P = 0.014), and more abdominal subcutaneous adipose tissue (SAT, 595 ± 17 vs. 531 ± 17 cm², P = 0.025) but not visceral fat (P = 0.739), than obese homozygotes for the wild‐type allele. Only SAT was greater in normal‐weight subjects with the insertion allele (P = 0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild‐type allele in the normal‐weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat‐free soft tissue mass and fat mass, particularly SAT, in obese black South African women.     

Triglyceride‐to‐HDL‐cholesterol Ratio and Metabolic Syndrome as Contributors to Cardiovascular Risk in Overweight Patients

Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL) ≥3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was ≥3.0 in 97 patients (group A) and <3.0 in 204 (group B). Overall, 93–97% of group A patients and 38–51% of group B patients had MS, depending on the diagnostic criterion. Group A patients with MS had significantly higher waist‐to‐hip ratio, total and non‐HDL cholesterol than group B patients with MS. In group B, MS and non‐MS patients had similar waist‐to‐hip ratio, blood pressure, total and non‐HDL cholesterol. Ten year coronary risk, calculated by the Framingham equations (n = 243), was 10.3 ± 5% in group B, non‐MS patients; 13.1 ± 6% in group B, MS patients; 19.9 ± 8% in group A (F = 32.8; P < 0.001). At the multiple regression analysis, TG/HDL ratio was associated with coronary risk (r² = 0.227) more closely than gender, blood pressure, waist‐to‐hip ratio, non HDL cholesterol, and MS considered as a whole. A separate regression analysis showed that the logarithmically transformed TG/HDL ratio, an index of the HDL cholesterol esterification rate, is also associated with coronary risk (r² = 0.252). Thus, TG/HDL ratio could help to characterize high‐risk overweight patients deserving a special therapeutic effort. Cardiovascular risk profile of insulin‐sensitive patients, identified by lower values of this parameter, is only moderately affected by MS.     

Sphingolipid Content of Human Adipose Tissue: Relationship to Adiponectin and Insulin Resistance

Ceramides (Cer) are implicated in obesity‐associated skeletal muscle and perhaps adipocyte insulin resistance. We examined whether the sphingolipid content of human subcutaneous adipose tissue and plasma varies by obesity and sex as well as the relationship between ceramide content and metabolic indices. Abdominal subcutaneous adipose biopsies were performed on 12 lean adults (males = 6), 12 obese adults (males = 6) for measurement of sphingolipid content and activity of the main ceramide metabolism enzymes. Blood was sampled for glucose, insulin (to calculate homeostasis model assessment‐estimated insulin resistance (HOMA_IR)) adiponectin, and interleukin‐6 (IL‐6) concentrations. Compared to lean controls, total ceramide content (pg/adipocyte) was increased by 31% (P < 0.05) and 34% (P < 0.05) in obese females and males, respectively. In adipocytes from obese adults sphingosine, sphinganine, sphingosine‐1‐phosphate, C14‐Cer, C16‐Cer, and C24‐Cer were all increased. C18:1‐Cer was increased in obese males and C24:1‐Cer in obese females. For women only, there was a negative correlation between C16‐Cer ceramide and plasma adiponectin (r = ?0.77, P = 0.003) and a positive correlation between total ceramide content and HOMA_IR (r = 0.74, P = 0.006). For men only there were significant (at least P < 0.05), positive correlations between adipocyte Cer‐containing saturated fatty acid and plasma IL‐6 concentration. We conclude that the sexual dimorphism in adipose tissue behavior in humans extends to adipose tissue sphingolipid content its association with adiponectin, IL‐6 and insulin resistance.     

25‐Hydroxyvitamin D Concentration Correlates With Insulin‐Sensitivity and BMI in Obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25‐hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin‐sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin‐sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin‐sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50 nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low‐density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin‐sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = ?0.58; P = 0.01), PTH (r = ?0.44; P < 0.01), insulin‐sensitivity (r = 0.43; P < 0.01), total (r = ?0.34; P = 0.030) and LDL (r = ?0.40; P = 0.023) (but not high‐density lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin‐sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = ?0.52; P < 0.01), whereas insulin‐sensitivity was not significant. Our study suggested that there is no cause–effect relationship between vitamin D and insulin‐sensitivity. In obesity, both low 25(OH)D concentration and insulin‐resistance appear to be dependent on the increased body size.     

BMI vs. waist circumference for identifying vascular risk

Objective: Current guidelines recommend measurement of both BMI and waist circumference (WC) in individuals with BMI between 25.0 and 34.9 kg/m². We investigated the relative contributions of BMI and WC toward identifying risk of adverse vascular events in a community‐based sample. Methods and Procedures: We evaluated Framingham Study participants (n = 4,195 person‐examinations, 53% women) using pooled logistic regression to assess the incremental prognostic utility of WC in predicting risk of a first cardiovascular disease (CVD) event in the three BMI categories (normal, <25 kg/m²; overweight, 25 to <30 kg/m²; obese, ≥ 30 kg/m²) and to assess the incremental prognostic utility of BMI and WC separately for predicting risk of a first cardiovascular event. Results: On follow‐up (16 years), 430 participants (158 women) had experienced a first CVD event. In overweight women, but not in overweight men, larger WC was found to be an independent predictor of CVD incidence, longitudinally (in women, multivariable‐adjusted odds ratio (OR) per s.d. increment in WC 1.86, 95% confidence interval (CI) = 1.03–3.36, P = 0.04; in men adjusted OR per s.d. increment in WC 0.91, 95% CI 0.60–1.38, P = 0.66). In obese individuals and in those with normal BMI, WC was not associated independently with incident CVD. When BMI and WC were analyzed separately for predicting risk of a first cardiovascular event, the c statistics associated with the multivariable CVD models incorporating BMI vs. WC were nearly identical in men and women. Discussion: Knowledge of WC aids identification of vascular risk among overweight women. Among normal weight or obese women and men (regardless of BMI category) WC did not appear to substantially add to prediction of risk of vascular events.