Increased Susceptibility to Insulin Resistance Associated with Abdominal Obesity in Aging Rats**

Objective: Recent data have suggested that the insulin resistance observed with aging may be more related to adiposity than aging per se. We asked whether the insulin resistance observed in aged rats was comparable (both in magnitude and location) to that of fat‐fed rats. Research Methods and Procedures: We performed hyperinsulinemic (5 mU/min per kg) euglycemic clamps with tracer in conscious, 6‐hour fasted young (YL), fat‐fed young (YF), fat‐fed old (OF), and calorically restricted old (OL) rats. Results: Intraabdominal fat measurements showed that OF and YF rats were more obese than YL (p ≤ 0.001; YF > OF > YL). Caloric restriction not only prevented age‐related obesity but also reduced the ratio of intraabdominal fat to lean body mass (LBM) compared with YL (OL: 0.59 ± 0.05 vs. YL: 1.07 ± 0.04; p = 0.017). Despite similar incremental insulin, YF and OF rats required 40% less infused glucose to maintain euglycemia than YL and OL rats (p < 0.001). Insulin‐stimulated glucose uptake (Si_Rd: ΔRd/(ΔInsulin × Glucose_SS) was impaired in OF rats (OF: 14.03 ± 1.79 vs. YL: 23.08 ± 1.87 × 10³ dL/min × kg LBM per pM; p = 0.004) and improved in OL rats (29.41 ± 1.84 × 10³ dL/min × kg LBM per pM; p = 0.031) compared with YL. Despite greater obesity, YF rats did not exhibit lower Si_Rd compared with OF rats (p = 0.58). In contrast, the ability of insulin to suppress endogenous glucose production (EGP; Si_EGP: ΔEGP/(ΔInsulin × Glucose_SS) was not impaired in OF rats (OF vs. YL; p = 0.61) but was markedly impaired in YF rats by ～75% (1.72 ± 0.66 × 10³ dL/min × kg per pM; p = 0.013). Surprisingly, separate regression analysis for old and young animals revealed that old rats exhibited a significantly steeper regression between Si (Rd and EGP) and adiposity than young rats (p < 0.05). Thus, older rats showed a proportionately greater decrement in insulin sensitivity with an equivalent increase in adiposity. Discussion: These data suggest that, in rodents, youth affords significant protection against obesity‐induced insulin resistance.     

Tripterygium Glycosides Impairs the Proliferation of Granulosa Cells and Decreases the Reproductive Outcomes in Female Rats

This study was carried out to investigate the impact of tripterygium glycosides (TGs) on ovarian function of female rats in vitro and in vivo. In vitro studies showed that TG induced cells decrease at G1 phase and inhibited cell proliferation in rat granulosa cells. In vivo, female rats were intragastrically administered with TG at the dose of 60 mg/kg/day for consecutive 50 days. TG caused a prolonged estrous cycle, and a significant reduction in ovarian index, serum E₂ level, and numbers of secondary and antral follicles (p < 0.05) in these rats. A significant reduction of viable embryos was demonstrated in TG‐treated female rats after mating (p < 0.01). Further, we observed observed the reduced expression level of TGF‐β1 after TG treatment in vitro and in vivo. Moreover, the expression of Smad2 and AKT was also decreased after TG treatment. These results suggest that TG can impair ovarian function through Smads‐mediated TGF‐β1 signal pathway     

Effect of Rosiglitazone on Insulin Sensitivity and Body Composition in Type 2 Diabetic Patients

Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes. Research Methods and Procedures: We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment. Results: There was a significant improvement in glycemic control (glycosylated hemoglobin −0.7 ± 0.7%, p ≤ 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 ± 14.5 μmol glucose/min/kg free fat mass, p < 0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (p ≤ 0.05) with RSG (2.1 ± 2.0 kg and 1.4 ± 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 ± 28.7 cm², p = 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (−6.7 ± 9.7%, concentration relative to water). Discussion: Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.     

S 23521 Decreases Food Intake and Body Weight Gain in Diet‐Induced Obese Rats

Objective: To investigate the effect of S 23521, a new glucagon‐like peptide‐1‐(7‐36) amide analogue, on food intake and body weight gain in obese rats, as well as on gene expression of several proteins involved in energy homeostasis. Research Methods and Procedures: Lean and diet‐induced obese rats were treated with either S 23521 or vehicle. S 23521 was given either intraperitoneally (10 or 100 μg/kg) or subcutaneously (100 μg/kg) for 14 and 20 days, respectively. Because the low‐dose treatment did not affect food intake and body weight, the subcutaneous treatment at high dose was selected to test the effect on selected end‐points. Results: Treated obese rats significantly decreased their cumulative energy intake in relation to vehicle‐treated counterparts (3401 ± 65 vs. 3898 ± 72 kcal/kg per 20 days; p < 0.05). Moreover, their body weight gain was reduced by 110%, adiposity was reduced by 20%, and plasma triglyceride levels were reduced by 38%. The treatment also improved glucose tolerance and insulin sensitivity of obese rats. Regarding gene expression, no changes in uncoupling protein‐1, uncoupling protein‐3, leptin, resistin, and peroxisome proliferator‐activated receptor (PPAR)‐γ were observed. Discussion: S 23521 is an effective glucagon‐like peptide‐1‐(7‐36) amide analogue, which induced a decrease in energy intake, body weight, and adiposity in a rat model of diet‐induced obesity. In addition, the treatment also improved glucose tolerance and insulin sensitivity of obese rats. These results strongly support S 23521 as a putative molecule for the treatment of obesity.     

Increased A‐ring Reduction of Glucocorticoids in Obese Zucker Rats: Effects of Insulin Sensitization

Objective: Obesity is associated with altered glucocorticoid metabolism, which may impact on hypothalamic‐pituitary‐adrenal axis activity. Here we characterize hepatic 5α‐ and 5β‐reductase in obese rats and their responses to insulin sensitization. Research Methods and Procedures: Hepatic A‐ring reductase protein and mRNA were assessed in lean and obese Zucker rats after insulin sensitization with metformin or rosiglitazone (n = 7 to 8/group). Results: Hepatic 5α‐reductase 1 and 5β‐reductase mRNA and protein (p < 0.01) were increased in obese rats. Insulin sensitization ameliorated increased 5α‐reductase 1 mRNA in obese rats (p < 0.01) and partially reversed increased 5β‐reductase activity. Discussion: Hepatic clearance of glucocorticoids by 5α‐ and 5β‐reductase is increased in obese Zucker rats, and this increase in clearance is attenuated by insulin sensitization. This increased hepatic clearance may underpin compensatory activation of the hypothalamic‐pituitary‐adrenal axis in obesity.     

Insulin Action,Regional Fat,and Myocyte Lipid: Altered Relationships with Increased Adiposity

Objective: Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity. Research Methods and Procedures: Myocyte triglyceride content (¹H‐magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.1 ± 7.8 years) with a broad range of adiposity (BMI 28.6 ± 4.1 kg/m², range 20.1 to 37.6 kg/m²). Results: Relationships between insulin‐stimulated glucose disposal and regional body fat depots appeared more appropriately described by nonlinear than linear models. When the group was subdivided using median total body fat as the cut‐point, insulin‐stimulated glucose disposal correlated negatively to all regional body fat measures (all p ≤ 0.004), serum triglycerides and free fatty acids (p < 0.02), and both soleus intramyocellular lipid (p = 0.003) and vastus lateralis triglyceride (p = 0.04) in the normal/less overweight group. In contrast, only visceral abdominal fat showed significant negative correlation with insulin‐stimulated glucose disposal in more overweight men (r = ?0.576, p = 0.01), some of whom surprisingly had lower than expected myocyte lipid levels. These findings persisted when the group was subdivided using different cut‐points or measures of adiposity. Discussion: Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.     

Possible Role of Triacylglycerol-Rich Lipoproteins in the Down-Regulation of Adipose Obese mRNA Expression in Rats Re-Fed a High-Fat Diet

Summary The large amount of absorbed dietary lipid after feeding a high-fat diet is mainly transported as triacylglycerol (TG)-rich lipoproteins (TRL) in the post-prandial blood and is subsequently distributed to peripheral tissues including adipose and muscle tissues. An in vivo and an in vitro study were conducted to investigate the possible role of post-prandial TRL after high fat feeding in the regulation of obese (ob) gene expression. Adult male Wistar rats were fasted for 48 h and re-fed either a fat-free/high-carbohydrate diet or a high-fat diet for 2, 4, or 8 h and plasma glucose, insulin, TG, and leptin as well as ob mRNA expression in epididymal fat pads were examined. Rats re-fed the high-fat diet had significantly higher plasma TG (p<0.05) and lower plasma leptin and adipose ob mRNA (p<0.05) than those fed the fat-free/high-carbohydrate diet; however, plasma glucose and insulin concentrations were not significantly different between the two groups. Plasma lipid analysis found large amount of TRL in rats fed with high-fat diet; however, only very small amount of the TRL was found in rats fed with fat-free/high-carbohydrate diet. We speculated that TRL might involve in regulation of ob gene expression. To further examine the regulation of TRL on ob mRNA expression, differentiated 3T3-L1 adipocytes were treated with TRL collected from rats fed 5 ml soybean oil by gastric intubations. TRL down-regulated ob mRNA not only in a dose and time dependent manner but also in the presence of insulin in 3T3-L1 adipocytes. These results suggest a possible role of TRL in the down-regulation of adipose ob mRNA expression and may account, at least in part, for the previous observations that short-term high fat feeding resulted in lower plasma leptin.     

Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability

Objective: To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability. Research Methods and Procedures: We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic‐euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL; by ¹H‐magnetic resonance spectroscopy). Our cohort included normal weight to obese men (n = 36). Results: Plasma adiponectin was directly associated with insulin sensitivity and high‐density lipoprotein‐cholesterol and inversely with plasma triglycerides but not IMCL. These findings are consistent with adiponectin promoting lipid uptake and subsequent oxidation in muscle and inhibiting TG synthesis in the liver. In multiple regression models that also included visceral and total fat, free fatty acids, TGs, and IMCL, either alone or in combination, adiponectin independently predicted insulin sensitivity, consistent with some of its insulin‐sensitizing effects being mediated through mechanisms other than modulation of lipid metabolism. Because VAT directly correlated with total fat and all three indices of local lipid availability, free fatty acids, and IMCL, an efficient regression model of insulin sensitivity (R² = 0.69, p < 0.0001) contained only VAT (part R² = 0.12, p < 0.002) and adiponectin (part R² = 0.41, p < 0.0001) as independent variables. Discussion: Given the broad range of total adiposity and body fat distribution in our cohort, we suggest that insulin sensitivity is robustly associated with adiponectin and VAT.     

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.     

Relation of Leptin to Insulin Resistance Syndrome in Children

Objectives: To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children. Research Methods and Procedures: Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11‐ to 14‐year‐old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (M_lbm). Children were divided by median BMI (boys = 20.5 kg/m²; girls = 21.4 kg/m²) into below‐median (thin) and above‐median (heavy) groups. Correlation coefficients between log‐leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race. Results: BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, M_lbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and M_lbm in heavy children and with insulin in thin children. Discussion: Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long‐term consequences in the development of the obesity‐insulin resistance‐related cardiovascular risk profile.     

Visceral Adipose Tissue and Markers of the Insulin Resistance Syndrome in Obese Black and White Teenagers

Objective: To determine the relationships between visceral and general adiposity, cardiovascular fitness, and markers of the insulin resistance syndrome in obese black and white teenagers. Research Methods and Procedures: Cross‐sectional survey of 81 obese 13‐ to 16‐year‐old youths. Visceral adipose tissue was measured with magnetic resonance imaging, and percentage body fat was measured with dual‐energy X‐ray absorptiometry. Cardiovascular fitness was assessed with a submaximal treadmill test. Fasting blood samples were analyzed for lipids/lipoproteins and insulin. Resting blood pressure was obtained using an automated cuff. Results: Visceral adipose tissue was significantly correlated with unfavorable levels of: triacylglycerol (r = 0.27, p < 0.05), total cholesterol (r = 0.27, p < 0.05), high‐density lipoprotein cholesterol (r = ?0.26, p < 0.05), the ratio of total cholesterol/high‐density lipoprotein cholesterol (r = 0.42, p < 0.01), low‐density lipoprotein cholesterol (r = 0.27, p < 0.05), apolipoprotein B (r = 0.38, p < 0.01), and systolic blood pressure (r = 0.30, p < 0.01). Multiple regression analyses revealed that visceral adipose tissue was more powerful than percentage body fat for explaining variance in lipoproteins (e.g., for the ratio of total cholesterol/high‐density lipoprotein cholesterol, r² = 0.13, p < 0.01, and for systolic blood pressure, r² = 0.07, p < 0.05). Ethnicity was the most powerful of the demographic predictors for blood lipids (r² = 0.15 for triacylglycerol with lower levels in blacks; r² = 0.10 for high‐density lipoprotein cholesterol with higher levels in blacks; r² = 0.06 for the ratio of total cholesterol/high‐density lipoprotein cholesterol with lower levels in blacks). Cardiovascular fitness was not retained as a significant predictor of markers of the insulin resistance syndrome. Discussion: Some of the deleterious relationships between visceral adiposity and markers for the insulin resistance syndrome seen in adults were already present in these obese young people.     

Monocyte chemoattractant protein-1 in obesity and type 2 diabetes. Insulin sensitivity study

Objective: Our goal was to test any association between human plasma circulating levels of monocyte chemoattractant protein‐1 (cMCP‐1) and insulin resistance and to compare monocyte chemoattractant protein‐1 (MCP‐1) adipose tissue gene expression and cMCP‐1 in relation with inflammatory markers. Research Methods and Procedures: cMCP‐1 was measured in n = 116 consecutive control male subjects to whom an insulin sensitivity (S_i) test was performed. Circulating levels of soluble CD14, soluble tumor necrosis factor receptor type 2 (sTNFR2), soluble interleukin‐6 (sIL‐6), and adiponectin also were measured. Subcutaneous adipose tissue samples were obtained from n = 107 non‐diabetic and type 2 diabetic subjects with different degrees of obesity. Real‐time polymerase chain reaction was used to measure gene expression of MCP‐1, CD68, tumor necrosis factor‐α (TNF‐α), and its receptor TNFR2. Results: In the S_i study, no independent effect of cMCP‐1 levels on insulin sensitivity was observed. In the expression study, in non‐diabetic subjects, MCP‐1 mRNA had a positive correlation with BMI (r = 0.407, p = 0.003), TNF‐α mRNA (r = 0.419, p = 0.002), and TNFR2 mRNA (r = 0.410, p = 0.003). In these subjects, cMCP‐1 was found to correlate with waist‐to‐hip ratio (r = 0.322, p = 0.048). In patients with type 2 diabetes, MCP‐1 mRNA was up‐regulated compared with non‐diabetic subjects. TNF‐α mRNA was found to independently contribute to MCP‐1 mRNA expression. In this group, CD68 mRNA was found to correlate with BMI (r = 0.455, p = 0.001). Discussion: cMCP‐1 is not associated with insulin sensitivity in apparently healthy men. TNF‐α is the inflammatory cytokine associated with MCP‐1 expression in subcutaneous adipose tissue.     

Diabetic modifier QTLs in F2 intercrosses carrying homozygous transgene of TGF-β

When the homozygous active form of porcine TGF-β1 transgene (Tgf/Tgf) (under control of the rat glucagon promoter) is introduced into the nonobese diabetic mouse (NOD) genetic background, the mice develop endocrine and exocrine pancreatic hypoplasia, low serum insulin concentrations, and impaired glucose tolerance. To identify genetic modifiers of the diabetic phenotypes, we crossed hemizygous NOD-Tgf with DBA/2J mice (D2) or C3H/HeJ mice (C3H) and used the “transgenic mice” for quantitative trait loci (QTL) analysis. Genome-wide scans of F₂-D Tgf/Tgf (D2 × NOD) and F₂-C Tgf/Tgf (C3H × NOD), homozygous for the TGF-β1 transgene, identified six statistically significant modifier QTLs: one QTL (Tdn1) in F₂-D Tgf/Tgf, and five QTLs (Tcn1 to Tcn5) in F₂-C Tgf/Tgf. Tdn1 (Chr 13, LOD = 4.39), and Tcn3 (Chr 2, LOD = 4.94) showed linkage to body weight at 8 weeks of age. Tcn2 (Chr 7, LOD = 4.38) and Tcn4 (Chr 14, LOD = 3.99 and 3.78) showed linkage to blood glucose (BG) concentrations in ipGTT at 30, 0, and 120 min, respectively. Tcn1 (Chr 1, LOD = 4.41) and Tcn5 (Chr 18, LOD = 4.99) showed linkage to serum insulin concentrations in ipGTT at 30 min. Tcn2 includes the candidate gene, uncoupling protein 2 (Ucp2), and shows linkage to Ucp2 mRNA levels in the soleus muscle (LOD = 4.90). Identification of six QTLs for diabetes-related traits in F₂-D Tgf/Tgf and F₂-C Tgf/Tgf raises the possibility of identifying candidate susceptibility genes and new targets for drug development for human type 2 diabetes. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Insulin Sensitivity,Cardiorespiratory Fitness,and Physical Activity in Overweight Hispanic Youth

Objective: To determine whether cardiorespiratory fitness and/or physical activity (PA) were related to measures of insulin sensitivity and secretion independent of body composition in overweight Hispanic children. Research Methods and Procedures: Ninety‐five Hispanic children (n = 55 boys; n = 40 girls; 8 to 13 years old) participated in this investigation. The frequently sampled intravenous glucose tolerance test was used to determine the insulin sensitivity index (SI), the acute insulin response, and the disposition index. Cardiorespiratory fitness [maximal oxygen uptake (Vo_2max)] was evaluated using a treadmill protocol, and PA was determined by an interviewer‐administered questionnaire. Body composition was measured using DXA. Results: Unadjusted correlations indicated that Vo_2max (milliliters of O₂ per minute) was negatively related to SI (r = ?0.46, p < 0.05) and disposition index (r = ?0.31, p < 0.05) and positively associated with fasting insulin (r = 0.29, p < 0.05), but these relationships were no longer significant once gender, Tanner stage, fat mass, and soft lean tissue mass were included as covariates (all p > 0.05). Multivariate linear regression analysis showed that body fat mass explained 53% of the variance in SI and that Vo_2max (milliliters of O₂ per minute) was not independently related to SI. Cardiorespiratory fitness was positively related to both fat mass (r = 0.43, p < 0.001) and soft lean tissue mass (r = 0.89, p < 0.001). PA was not related to any measure of insulin sensitivity and secretion. Discussion: Cardiorespiratory fitness, as determined by Vo_2max (milliliters of O₂ per minute), was not independently related to insulin sensitivity or secretion, suggesting that Vo_2max influences insulin dynamics indirectly through fat mass.     

Pleiotropic Effects of Genes for Insulin Resistance on Adiposity in Baboons

Objective: Previous research has suggested a genetic contribution to the development of insulin resistance and obesity. We hypothesized that the same genes influencing insulin resistance might also contribute to the variation in adiposity. Research Methods and Procedures: A total of 601 (200 male, 401 female) adult baboons (Papio hamadryas) from nine families with pedigrees ranging in size from 43 to 121 were used in this study. Plasma insulin, glucose, C‐peptide, and adiponectin were analyzed, and homeostasis model assessment of insulin resistance (HOMA IR) was calculated. Fat biopsies were collected from omental fat tissue, and triglyceride concentration per gram of fat tissue was determined. Body weight and length were measured, and BMI was derived. Univariate and bivariate quantitative genetic analyses were performed using SOLAR. Results: Insulin, glucose, C‐peptide, and adiponectin levels, HOMA IR, triglyceride concentration of fat tissue, body weight, and BMI were all found to be significantly heritable, with heritabilities ranging from 0.15 to 0.80. Positive genetic correlations (r_Gs) were observed for HOMA IR with C‐peptide (r_G = 0.88 ± 0.10, p = 0.01), triglyceride concentration in fat tissue (r_G = 0.86 ± 0.33, p = 0.02), weight (r_G = 0.50 ± 0.20, p = 0.03), and BMI (r_G = 0.64 ± 0.22, p = 0.02). Discussion: These results suggest that a set of genes contributing to insulin resistance also influence general and central adiposity phenotypes. Further genetic research in a larger sample size is needed to identify the common genes that constitute the genetic basis for the development of insulin resistance and obesity.     

Spousal Resemblance and Risk of 7-Year Increases in Obesity and Central Adiposity in the Canadian Population

KATZMARZYK, PETER T., LOUIS PÉRUSSE, D. C. RAO, AND CLAUDE BOUCHARD. Spousal resemblance and risk of 7-year increases in obesity and central adiposity in the Canadian population. Obes Res. Objective: Spousal similarities in 7-year changes in obesity and obesity-related phenotypes were examined in a sub-sample of 376 pairs of spouses from a sample of 1487 participants in the 1988 Campbell's Survey follow-up of the 1981 Canada Fitness Survey. Measures: Indicators of body fatness included the body mass index (BMI), the sum of five skinfolds (SF5), and waist circumference (WAIST), whereas those for relative adipose tissue (AT) distribution included the ratio of two trunk to three extremity skinfolds, adjusted for SF5 (TER_adj), and WAIST adjusted for BMI (WAIST_adj). Results: Spouse correlations were 0. 17, 0. 17, and 0. 17 for the BMI (p<0. 05) and 0. 20, 0. 20, and 0. 21 for SF5 (p<0. 05) for the initial measurement, follow-up, and 7-year change, respectively. Spouse correlations for WAIST were somewhat lower: 0. 16 (p<0. 05), 0. 11 (p<0. 05), and 0. 11 (p<0. 05) for the initial measurement, follow-up, and 7-year change, respectively, whereas those for TER_adj and WAIST_adj were low and not significant. Spouses of probands who had increases in adiposity and central AT distribution had elevated risks of also increasing in these parameters. Spousal risks (risk ratios) were 1. 48 (95% CI = 1. 08-2. 03), 1. 49 (95% CI= 1. 10-2. 02), and 1. 68 (95% CI= 1. 28-2. 21) for increases in BMI, SF5, and WAIST, respectively, whereas the risks for increases in central adiposity were 1. 22 (95% CI = 0. 86-1-73), and 1. 05 (95% CI = 0. 72–153) for TER_adj, and WAIST_adj, respectively. Discussion: The results indicate significant spousal resemblance and risk for increases in fatness in the general Canadian population, whereas both the spousal resemblance and risks for increases in AT distribution, adjusted for level of fatness, are non-significant. The results suggest that shared environmental factors may be important determinants of spousal similarities in changes in total body fatness over time; however, cohabitation in the short term may not lead to increases in spousal resemblance.     

Adolescent Sex Differences in Adiponectin Are Conditional on Pubertal Development and Adiposity

Objective: Adiponectin is an adipose tissue protein with important insulin‐sensitizing, anti‐inflammatory, and cardioprotective properties but is paradoxically lower in obese individuals. Sex differences in adiponectin have been reported in adults and adolescents but not in prepubertal children. In this study, we hypothesized that sex differences in adiponectin would develop during puberty and would be influenced by level of adiposity. Research Methods and Procedures: Adiponectin levels were measured in 1196 white and African‐American adolescents. Insulin resistance was estimated using the homeostasis model (HOMA‐IR). Demographic, developmental, and metabolic variables, including interactions with adiposity measurements, were evaluated for independent relationships with adiponectin levels. Results: Overall, adiponectin levels varied significantly by sex, race, adiposity, and puberty stage. Significant sex differences in adiponectin developed after the onset of puberty, particularly in lean adolescents. Adolescent boys had lower adiponectin levels in post‐puberty compared with pre‐puberty (p = 0.01) and had lower levels than girls in both puberty and post‐puberty (both p < 0.001), after adjusting for race, BMI z‐score, and natural logarithm‐(HOMA‐IR). Sex differences were also conditional on adiposity level, with significant sex differences among lean (p < 0.001) but not among non‐lean (p = 0.16) adolescents. Adiponectin levels in girls decreased more with increasing adiposity than in boys (p = 0.004), but only marginally so after standardizing for girls’ higher mean adiponectin level (p = 0.11). Discussion: Sex differences in adiponectin are dependent on both puberty stage and adiposity in adolescents, such that by post‐puberty, non‐lean boys exhibit the lowest levels of adiponectin.