Total and Regional Fat and Serum Cardiovascular Disease Risk Factors in Lean and Obese Children and Adolescents

Objective: This study was conducted to evaluate the association of total and central adiposity with serum cardiovascular disease (CVD) risk factors in lean and obese Portuguese children and adolescents. Research Methods and Procedures: A total of 87 girls (13.2 ± 1.6 years old, 29.9 ± 6.4% body fat [mean ± SD]) and 72 boys (13.2 ± 1.6 years old, 20.8 ± 9.9% body fat) volunteered for the study. Whole‐body composition and fat distribution, from DXA and anthropometry, and serum lipids, lipoproteins, and apolipoproteins were evaluated. Results: The sum of three trunk skinfolds (STS) was highly correlated with total trunk fat mass measured by DXA (p < 0.001). Body mass index, DXA‐measured percentage of body fat, trunk fat mass, STS, and the waist‐to‐height ratio were generally found to be associated with triacylglycerol, the ratio of total cholesterol (TC) to high density lipoprotein‐cholesterol (HDL‐C), low density lipoprotein‐cholesterol (LDL‐C), and apolipoprotein B levels, (significant age‐adjusted r between 0.16 and 0.27, p < 0.05). Body mass index, STS, and the waist circumference were also associated with HDL‐C (p < 0.05), whereas no body composition variable significantly correlated with TC or apolipoproteins A‐I. The STS was significantly correlated with HDL‐C (p < 0.01), TC/HDL‐C (p < 0.05), and apolipoproteins A‐I (p < 0.05) independently of whole‐body fatness. Obese subjects (n = 73) had higher TC, LDL‐C, TC/HDL‐C, and apolipoprotein B than did non‐obese subjects (n = 86), and significant associations between central adiposity and some lipid variables (triacylglycerol and HDL‐C) were found in obese children and adolescents that were not present in leaner individuals. Discussion: DXA‐ and anthropometry‐based whole‐body and central fat measures are associated with serum CVD risk factors in Portuguese boys and girls. Obese children and adolescents have a poorer lipid profile than do their leaner counterparts. Trunk skinfolds, which are easy to obtain even in large samples, predict CVD risk factors to the same extent as DXA‐based variables, in some cases, independently of total fatness.     

Gender specific effect of LIPC C‐514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children

Hepatic lipase (LIPC) is a key rate‐limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C‐514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case‐controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C‐514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta‐analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL‐C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL‐C) in obese boys, and triglyceride (TG), TC and LDL‐C in non‐obese girls (all P < 0.05). In the meta‐analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL‐C in the overall and boys, and LDL‐C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta‐analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.     

The Val103Ile Polymorphism of Melanocortin‐4 Receptor Regulates Energy Expenditure and Weight Gain

Objective: The melanocortin‐4 receptor (MC4R) regulates energy intake. On the basis of animal studies, it may also regulate energy expenditure. Research Methods and Procedures: The effect of the Val103Ile polymorphism of the MC4R gene on energy metabolism was studied in 229 middle‐aged nondiabetic subjects (Group 1, age 51.2 ± 9.8 years, BMI 26.8 ± 4.5 kg/m²) and on weight gain in 1013 elderly subjects (Group 2, age 69.9 ± 2.9 years, BMI 27.4 ± 4.1 kg/m²) during a 3.5‐year follow‐up study. In Group 1, insulin sensitivity, energy expenditure, and substrate oxidation were measured with the hyperinsulinemic euglycemic clamp combined with indirect calorimetry. Results: In Group 1, the Val103Ile genotype was associated with high rates of energy expenditure (63.42 ± 13.40 in eight subjects with the Val103Ile genotype vs. 59.86 ± 7.33 J/kg per minute in 221 subjects with the Val103Val genotype, p = 0.007), high rates of glucose oxidation (8.90 ± 6.15 vs. 6.07 ± 4.38 μmol/kg per minute, p = 0.020), and low levels of free fatty acids (0.45 ± 0.18 vs. 0.56 ± 0.23 mM, p = 0.029) in the fasting state, and with high rates of glucose oxidation during the clamp (18.88 ± 4.63 vs. 17.60 ± 3.24 μmol/kg per minute, p = 0.031). In Group 2, the 103Ile allele was associated with an increase in weight gain during the follow‐up (0.78 ± 3.98 vs. ?0.82 ± 3.98 kg, p = 0.038). Discussion: The Val103Ile polymorphism of the MC4R gene is associated with energy expenditure in humans. Furthermore, it may associate with glucose oxidation, free fatty acid levels, and weight gain.     

Cholesteryl ester transfer protein in metabolic syndrome

Objective: Low high‐density lipoprotein cholesterol (HDL‐C), hypertriglyceridemia, and small dense‐low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG‐rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL‐C and small dense‐LDL. The aim of this study was to investigate the role of CETP in subjects with MS. Research Methods and Procedures: In a cross‐sectional cohort of 234 middle‐aged men and 252 women randomly selected from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study, MS was diagnosed according to the National Cholesterol Education Program guidelines. CETP mass was determined by enzyme‐linked immunosorbent assay and LDL size‐by‐gradient polyacrylamide gel electrophoresis. Results: Men and women with MS had lower HDL‐C (45 ± 7 vs. 58 ± 13 and 48 ± 10 vs. 71 ± 14 mg/dL for men and women, respectively; p < 0.001 for all) and higher TG levels (222 ± 71 vs. 98 ± 54 and 167 ± 67 vs. 90 ± 35 mg/dL for men and women, respectively; p < 0.001 for all) than healthy subjects. LDL size was lower in subjects with MS (256 ± 11 Å vs. 267 ± 11 Å and 262 ± 10 Å vs. 273 ± 8 Å for men and women, respectively; p < 0.001 for all). CETP mass was higher in men with MS (1.87 ± 0.78 vs. 1.40 ± 0.65 μg/mL; p < 0.001) but not in women (1.74 ± 0.79 vs. 1.62 ± 0.62 μg/mL). CETP mass correlated inversely with LDL size in both men and women (r = ?0.19, p < 0.01 and r = ?0.13, p < 0.05 in men and women, respectively). Discussion: MS is associated with increased CETP mass in men. Increased CETP mass may be responsible for reduced HDL‐C and reduced LDL particle diameter in MS.     

Gender‐Specific Association of a Perilipin Gene Haplotype with Obesity Risk in a White Population

Objective: Perilipin is a class of protein‐coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single‐nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. Research Methods and Procedures: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI ≥ 30 kg/m². Results: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men. Discussion: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.     

Anti‐lipolytic Effects of Insulin in African American and White Prepubertal Boys

Objective: Relative to whites, African Americans have lower circulating triglycerides (TG) and greater highdensity lipoprotein cholesterol. The metabolic basis for this difference is not known. This study was conducted to test the hypothesis that insulin‐induced suppression of free fatty acids (FFA) results in lower serum TG in African American versus white prepubertal children. Research Methods and Procedures: Insulin, FFA, and TG were determined at baseline and during a frequently sampled, intravenous glucose tolerance test in eight African American and eight white prepubertal males pair‐matched for whole‐body insulin sensitivity. Results: Baseline TG was lower in African Americans (0.43 ± 0.10 vs. 0.79 ± 0.37 mM/L; mean ± SD; p < 0.01). African Americans had higher peak insulin (218 ± 102 vs. 100 ± 30 pM/L; mean ± SD; p < 0.01) and a greater acute insulin response (9282 ± 4272 vs. 4230 ± 1326 pM/L × 10 minutes; mean ± SD; p < 0.05). FFA and TG values determined at the FFA nadir were lower in African Americans (0.26 ± 0.02 vs. 0.30 ± 0.03 mEq/L; mean ± SD; p < 0.01 for FFA nadir and 0.49 ± 0.07 vs. 0.77 ± 0.33 mM/L; mean ± SD; p < 0.05 for TG). Among all subjects, FFA nadir was correlated with peak insulin (r = ?0.54; p < 0.05). After adjusting for FFA nadir, neither baseline nor postchallenge TG differed with ethnicity (p = 0.073 and 0.192, respectively). The ethnic difference in FFA nadir disappeared after adjusting for peak insulin (p = 0.073). Discussion: These data suggest that hyperinsulinemiainduced suppression of FFA among African Americans is a determinant of lower TG in this group.     

Effect of the Interleukin‐6 (−174) G/C Promoter Polymorphism on Adiponectin and Insulin Sensitivity

We investigated the relation among the interleukin (IL)‐6 (?174) G/C promoter polymorphism, adipose tissue gene expression of IL6, circulating adiponectin, and systemic insulin sensitivity. Eighty‐five Swedish male subjects who had participated in our previous prediabetic phenotype characterization study were genotyped for the IL6 (?174) G/C polymorphism. Subcutaneous adipose tissue gene expression of IL6 and adiponectin was measured in 44 subjects. The IL6 (?174) G allele carriers had higher fasting plasma insulin levels (C/C, 7.8 ± 1.1; G/C, 9.0 ± 0.6; G/G, 10.5 ± 1.0 mU/L) and higher homeostasis model assessment for insulin resistance (C/C, 1.6 ± 0.2; G/C, 1.9 ± 0.1; G/G, 2.2 ± 0.2) compared with subjects with the C/C genotype. The circulating adiponectin levels were lower in the G allele carriers (C/C, 7.93 ± 0.45; G/C, 7.05 ± 0.44; G/G, 7.02 ± 0.46 μg/mL), whereas the IL‐6 levels did not differ among the three genotypes. Adipose tissue IL6 gene expression was significantly higher in the G allele carriers compared with the subjects homozygous for the C allele (C/C, 0.29 ± 0.15; G/C, 0.84 ± 0.29; G/G, 0.62 ± 0.35). Our results suggest that IL6 (?174) G/C polymorphism is associated with insulin resistance and increased adipose tissue IL6 gene expression, which can impair adiponectin production.     

Association of the LCT-13910C>T polymorphism with obesity and its modulation by dairy products in a Mediterranean population

The ?13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity‐related variables and its modulation by dairy product intake in an elderly population. We studied 940 high‐cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome‐related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype was not associated with lower milk or dairy product consumption in the whole population. Only in women was dairy intake significantly lower in CC subjects. The most important association was obtained with anthropometric measurements. CC individuals had lower weight (P = 0.032), lower BMI (29.7 ± 4.2 vs. 30.6 ± 4.2 kg/m²; P = 0.003) and lower waist circumference (101.1 ± 11.8 vs. 103.5 ± 11.5 cm; P = 0.005) than T‐allele carriers. Obesity risk was also significantly higher in T‐allele carriers than in CC individuals (odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05–1.81; P = 0.01), and remained significant even after adjustment for sex, age, diabetes, physical activity, and energy intake. However, in subgroup analysis, these associations were found to be significant only among those consuming moderate or high lactose intakes (>8 g/day). No significant associations with lipids, glucose, or blood pressure were obtained after adjustment for BMI. In conclusion, despite not finding marked differences in dairy product consumption, this polymorphism was strongly associated with BMI and obesity and modulated by lactose intake in this Mediterranean population.     

The effects of Goami No. 2 rice, a natural fiber-rich rice, on body weight and lipid metabolism

Objective : Increased intake of dietary fiber reduces the risk of obesity and type 2 diabetes. We assessed the effects of a fiber‐rich diet on body weight, adipokine concentrations, and the metabolism of glucose and lipids in non‐obese and obese subjects in Korea, where rice is the main source of dietary carbohydrates. Research Methods and Procedures : Eleven healthy, non‐obese and 10 obese subjects completed two 4‐week phases of individual isoenergetic food intake. During the control diet phase, subjects consumed standard rice; during the modified diet phase, subjects consumed equal proportions of fiber‐rich Goami No. 2 rice and standard rice. We used a randomized, controlled, crossover study design with a washout period of 6 weeks between the two phases. Results : After the modified diet phase, body weight was significantly lower in both the non‐obese and obese subjects (non‐obese, 57.0 ± 2.9 vs. 56.1 ± 2.8 kg, p = 0.001; obese, 67.7 ± 2.1 vs. 65.7 ± 2.0 kg, p < 0.001 for before vs. after). The BMI was significantly lower in obese subjects (26.9 ± 0.5 vs. 26.0 ± 0.6 kg/m², p < 0.001). The modified diet was associated with lower serum triacylglycerol (p < 0.01), total cholesterol (p < 0.01), low‐density lipoprotein cholesterol (p < 0.05), and C‐peptide (p < 0.05) concentrations in the obese subjects. Discussion : These results indicate that fiber‐rich Goami No. 2 rice has beneficial effects and may be therapeutically useful for obese subjects.     

Association of the TNF‐α−308 G/A Promoter Polymorphism with Insulin Resistance in Obesity

Objective: Obesity is a major risk factor for the development of type 2 diabetes. Tumor necrosis factor (TNF)‐α is a candidate gene for the development of both obesity and insulin resistance. We investigated whether a common polymorphism in the promoter region (?308 G/A) of the TNF‐α gene was associated with increased risk for the development of insulin resistance and cardiovascular disease in an obese Australian population. Research Methods and Procedures: Obese, non‐diabetic subjects (146 women and 34 men) were genotyped with polymerase chain reaction‐restriction fragment length polymorphism techniques, and anthropometric and biochemical measurements were analyzed. A homeostasis model assessment (HOMA) score was used to gauge the level of insulin resistance. Results: The frequencies of the G allele and the A allele were 0.759 and 0.241, respectively. Subjects homozygous for the A allele had higher fasting insulin levels (226 vs. 131 pM; p < 0.001), higher HOMA scores (10.2 vs. 5.3; p < 0.001), higher systolic blood pressure (143 vs. 129 mm Hg; p = 0.02), and lower high‐density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p = 0.04) than did subjects homozygous for the G allele. Whereas an association between insulin resistance and body mass index or waist circumference was seen in all subjects, a highly significant negative correlation of HDL cholesterol to HOMA scores (r = ?0.710; p < 0.001) occurred in subjects with the A allele only. Discussion: The ?308 G/A TNF‐α gene variant conveys an increased risk for the development of insulin resistance in obese subjects. The presence of low HDL cholesterol levels further increases the risks associated with insulin resistance in carriers of the A allele.     

Apolipoprotein A‐II Polymorphism and Visceral Adiposity in African‐American and White Women

To determine the association between the ?265 T to C substitution in the apolipoprotein A‐II (APOA‐II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African‐American and white women, we genotyped 237 women (115 African‐American and 122 white) for this polymorphism. Body composition was assessed by DXA, and VAT was determined from a single computed tomography scan. In addition to VAT, we examined the association between the polymorphism and other phenotypes (total body fat, total abdominal adipose tissue, and subcutaneous abdominal adipose tissue). The mutant C allele in the APOA‐II gene was less frequent in African‐American compared with white women, 23% vs. 36%, respectively (p < 0.01). VAT was significantly higher in carriers of the C allele compared with noncarriers after adjustment for total body fat (p < 0.05). When separate analyses by ethnic group were conducted, the association between the polymorphism and VAT was observed in white (p < 0.05) but not African‐American (p = 0.57) women. There was no association between the polymorphism and the other phenotypes. These results indicate a significant association between the T265C APOA‐II polymorphism and levels of VAT in premenopausal women. This association is present in white but not African‐American women.     

Body Weight Modulates Cholesterol Metabolism in Non‐Insulin Dependent Type 2 Diabetics

Objective: Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes. Research Methods and Procedures: Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios. Results: The study population was divided into normal‐weight (body mass index, 24.1 ± 0.4 kg/m²; mean ± SEM; n = 20) and obese (31.0 ± 0.5 kg/m²; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 ± 78 vs. 1077 ± 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 ± 1 vs. 40 ± 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non‐obese groups. Serum sex hormone‐binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R² = 24%) and body mass index (R² = 15%) were the only variables explaining the variability of cholesterol synthesis. Discussion: Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.     

Association analysis of the E-selectin 98G > T polymorphism and the risk of childhood ischemic stroke

Genes related to platelet and arterial endothelial function have been recently considered as independent risk factors for stroke. We aimed to analyze a relationship between the E‐selectin 98G > T polymorphism and stroke in children and to observe the transmission of E‐selectin alleles from heterozygous parents to their affected children. We studied 59 children after stroke, 112 parents, and 87 healthy children. The E‐selectin 98G > T polymorphism was analyzed with the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. The frequency of the 98T allele in patients was almost twofold lower than in controls (5.1% vs. 9.8%, p = 0.145, odds ratios (OR) = 0.49) as well as carriers of the 98T allele (19.5% in controls vs. 8.5% in cases, p = 0.067, OR = 0.38). The G allele of the E‐selectin 98G > T polymorphism was more frequently transmitted to the children after stroke compared to the T allele (68% vs. 32%). In conclusion, we did not confirm the relationship between the 98G > T polymorphism of the E‐selectin gene and childhood ischemic stroke. There is still a need for further studies. Copyright © 2010 John Wiley & Sons, Ltd.     

Increased Serum Cholesteryl Ester Transfer Protein in Obese Children

Objective: To determine whether serum cholesteryl ester transfer protein (CETP), which is one of the physiologically active gene products secreted from adipose tissue, is increased and associated with atherogenic lipoprotein profile in obese children. Research Methods and Procedures: Subjects were 42 consecutive outpatient Japanese obese children, 29 boys and 13 girls, ranging in age from 5 to 14 years, and 25 age‐matched non‐obese children, 13 boys and 12 girls, as the control group for measuring CETP mass. Blood was drawn after an overnight fast and, at the same time, and anthropometric measurements including height, body weight, waist girth, hip girth, and triceps and subscapular skinfold thicknesses were taken. Paired samples were obtained from 15 obese children who underwent psychoeducational therapy. Serum CETP mass was assayed by an enzyme‐linked immunosorbent assay. Results: The serum levels of triglyceride, total cholesterol (TC), low‐density lipoprotein cholesterol, TC/high‐density lipoprotein cholesterol (HDLC), apolipoproteins (apo) B, apo B/apo A₁, and insulin in obese children were significantly higher than the respective reference values. Serum CETP level was ～2‐fold higher (98.7 ± 3.6 vs. 50.9 ± 4.0 nM, means ± SEM, p < 0.001) in the obese children than in the controls. In 15 obese children, whose percentage of overweight declined during therapy, CETP levels decreased significantly. CETP level was correlated with HDLC, TC/HDLC, and insulin, and with percentage of overweight when the data of the obese and non‐obese children were combined. Discussion: CETP is increased and associated with the atherogenic lipoprotein profile in obese children.     

An SNP in the Adiponectin Gene Is Associated with Decreased Serum Adiponectin Levels and Risk for Impaired Glucose Tolerance

Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p = 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 ± 0.24 μg/mL; G/T, 10.98 ± 0.32 μg/mL; T/T, 12.00 ± 0.92 μg/mL; p = 0.015) even after adjustment for sex, age, BMI, waist‐to‐hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p = 0.040). We found a significant negative association of circulating adiponectin levels with waist‐to‐hip ratio (r = ?0.42, p < 0.001), sagittal abdominal diameter (r = ?0.24, p < 0.001), triglycerides (r = ?0.32, p < 0.001), homeostasis model assessment index (r = ?0.14, p = 0.001), and uric acid (r = ?0.36, p < 0.001) and positive association with high‐density lipoprotein‐cholesterol (r = 0.41, p < 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.