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(G)s) 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.