title: HRASLS3 is a PPARgamma-selective target gene that promotes adipocyte differentiation.
abstract: The prevalence of obesity and its associated metabolic diseases worldwide has focused attention on understanding the mechanisms underlying adipogenesis. The nuclear receptor PPARgamma has emerged as a central regulator of adipose tissue function and formation. Despite the identification of numerous PPARgamma targets involved in a range of processes, from lipid droplet formation to adipokine secretion, information is still lacking on targets downstream of PPARgamma that directly affect fat cell differentiation. Here we identify HRASLS3 as a novel PPARgamma 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 PPARgamma 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 PPARgamma/RXR heterodimers. Finally, we show that overexpression of HRASLS3 augments PPARgamma-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 PPARgamma action in adipogenesis.
authors.affiliation: Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hummasti
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hong
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bensinger
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D041681:NIH 3T3 Cells; D047495:PPAR gamma / Q000378:metabolism*; D054512:Phospholipases A2, Calcium-Independent; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D047495:PPAR gamma; D011506:Proteins; D054512:Phospholipases A2, Calcium-Independent; C490066:Plaat3 protein, mouse