出版社：American Society for Biochemistry and Molecular Biology
摘要：The prevalence of obesity and its associated metabolic diseases worldwide has focused attention on understanding the mechanisms underlying adipogenesis. The nuclear receptor PPARγ has emerged as a central regulator of adipose tissue function and formation. Despite the identification of numerous PPARγ targets involved in a range of processes, from lipid droplet formation to adipokine secretion, information is still lacking on targets downstream of PPARγ that directly affect fat cell differentiation. Here we identify HRASLS3 as a novel PPARγ regulated gene with a role in adipogenesis. HRASLS3 expression increases during the differentiation of preadipocyte cell lines and is highly expressed in white and brown adipose tissue in mice. HRASLS3 expression is induced by PPARγ ligands in preadipocyte cell lines as well in adipose tissue in vivo. We demonstrate that the HRASLS3 promoter contains a functional PPAR response element and is a direct target for regulation by PPARγ/RXR heterodimers. Finally, we show that overexpression of HRASLS3 augments PPARγ-driven lipid accumulation and adipogenesis, whereas siRNA-mediated knockdown of HRASLS3 expression decreases differentiation. Together, these results identify HRASLS3 as one of the downstream effectors of PPARγ action in adipogenesis.
