Regulation of the expression of adiponectin, resistin, and GLUT4 in omental adipose tissue of baboon




Tejero-Barrera, Maria Elizabeth

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The purpose of this research was to identify the chromosomal regions influencing the mRNA expression of the hormones resistin and adiponectin, and the glucose transporter 4 (GLUT4) in omental adipose tissue of baboons. These baboon genes were cloned using a two-step reverse transcription- polymerase chain reaction (RT-PCR) technique. Real- time, quantitative RT-PCR assays were developed and standardized for measurement of mRNA levels of each gene. Total RNA was isolated from 460 samples of adipose tissue from adult pedigreed baboons, and used for the quantification of adiponectin, resistin and GLUT4 mRNA. Quantitative genetic analyses were conducted using the mRNA abundance of each gene as a quantitative phenotype applying the variance decomposition approach. Heritabilities were calculated for resistin (h2 = 0.23, p = 0.005), adiponectin (h2 = 0.23, p = 0.001) and GLUT4 (h2 = 0.24, p = 0.001). Genome scan analyses were conducted to locate the chromosomal regions influencing the expression of the studied genes. The identified regions and corresponding LOD scores are: 19p13 (LOD score = 3.8) for resistin, 6q13 (LOD score =1.6) for adiponectin mRNA and same location (LOD score =1.0) for adiponectin protein, and 10q24-26 (LOD score = 1.4) for GLUT4 mRNA. A parallel study in 120 baboons indicated a relationship between body weight and indicators for insulin sensitivity, and an association between adiponectin levels and insulin resistance (HOMA-IR index) in baboons. No correlation between the analyzed phenotypes and resistin expression in monocytes was found. The relationships between mRNA expression in adipose tissue of resistin, adiponectin and GLUT4 and circulating levels of selected cytokines (TNFa, IL-6 and IL-1b) and phenotypes associated to insulin resistance were investigated in a sub-sample of unrelated baboons (n=40). Resistin expression in adipose tissue was related to insulin sensitivity, adiponectin mRNA was inversely associated with cytokines in plasma, and GLUT4 abundance and the HOMA-IR index were correlated. Collectively, these results revealed novel findings on the genetic component of the endocrine function of adipose tissue, and confirmed the value of the baboon as a model for the genetic study of obesity-related conditions.