Identification of a single nucleotide polymorphism associated with adiposity following transcriptional profiling of gene expression in the anterior pituitary gland
Porter, Tom E
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Although the anterior pituitary secretes three hormones that affect metabolism and body fat stores, a comprehensive analysis of pituitary gene expression associated with body fat has not been performed. This research used cDNA microarrays to investigate pituitary gene expression in two chicken lines that were selected for low and high body fat (Lean and Fat). RNA was extracted from pituitaries at 1, 3, 5, and 7 weeks of age. 386 genes that showed significant differences in expression levels by line or in the line-by-age interaction were analyzed further. Differentially expressed genes between lines are potential candidates as genetic markers for high and low potential for body fat accumulation. One such candidate, the lysophosphatidic acid (LPA) receptor-1 (LPAR1), was identified as a potential marker, being differentially expressed between the 2 lines at the early ages. Genomic DNA from the Fat and Lean F0 generation was sequenced upstream of the LPAR1 coding region. A SNP consisting of a T to C transversion that introduces a GATA-1 transcription factor binding site was identified in the Lean line (Fisher's Exact Test, p &#8804; 0.001). The fattest and leanest animals of both sexes in the back-crossed F2 generation (n=48 each) were genotyped by allele-specific PCR, and an association was present between the genotype and phenotype (generalized linear model, p &#8804; 0.05). Expression of GATA transcription factors in mice inhibits differentiation of preadipocytes into mature adipocytes. LPAR1 also inhibits differentiation of preadipocytes in mice, and LPAR1 knock-out mice become significantly fatter than wild-type mice. A SNP that introduces a GATA site in the promoter of LPAR1 could up-regulate its expression in the Lean line, and increased LPA signaling could then inhibit preadipocyte differentiation. Conversely, loss of the GATA binding site could explain decreased levels of LPAR1 expression and attenuated inhibition of adipocyte maturation in the Fat line.