title: MiR-503 inhibits adipogenesis by targeting bone morphogenetic protein receptor 1a.
abstract: Adipogenesis plays a key role in the regulation of whole-body energy homeostasis and is critically related to obesity. To overcome obesity and its associated disorders, it is necessary to elucidate the molecular mechanisms involved in adipogenesis. An adipogenesis-related miRNA array analysis demonstrated that miR-503 was differentially expressed before and after adipocyte differentiation; however, the exact role of miR-503 in adipocyte differentiation is unclear. Thus, the objective of this study was to further examine miR-503 in adipocyte differentiation. We found significantly decreased expression of miR-503 during adipocyte differentiation process. Using bioinformatic analysis, miR-503 was identified as a potential regulator of Bone Morphogenetic Protein Receptor 1a (BMPR1a). We then validated BMPR1a as the target of miR-503 using a dual luciferase assay, and found decreased miR-503 and increased BMPR1a expression during adipogenesis. Overexpression of miR-503 in preadipocytes repressed expression of BMPR1a and adipogenic-related factors such as CCAAT/enhancer binding protein a (C/EBPα), proliferator-activated receptor-gamma (PPARγ), and adipocyte protein 2 (AP2). In addition, miR-503 overexpression impaired the phosphoinositol-3 kinase (PI3K)/Akt pathway. Inhibition of miR-503 had the opposite effect. Additionally, BMPR1a interference by siRNA attenuated adipocyte differentiation and the accumulation of lipid droplets via downregulating the PI3K/Akt signaling pathway. Our study provides the first evidence of the role miR-503 plays in adipocyte differentiation by regulating BMPR1a via the PI3K/Akt pathway, which may become a novel target for obesity therapy.
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Man
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Tan
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Hao-Neng
authors.initials: HN
authors.lastname: Tang
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Tang
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Ci-La
authors.initials: CL
authors.lastname: Zhou
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University Changsha City, Hunan Province, China.
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
keywords: Adipogenesis; BMPR1a; PI3K/Akt; miR-503