PPARγ-mediated G-protein coupled receptor 120 signaling pathway promotes transcriptional activation of miR-143 in adipocytes.

ABSTRACT

MicroRNAs (miRNAs), the small noncoding RNAs, regulate various biological processes such as adipogenesis. MicroRNA-143 (miR-143) promotes adipocyte differentiation, and is correlated with obesity in mice fed a high-fat diet. However, the transcriptional regulation of miR-143 is largely unknown. In this study, we identified that miR-143 is a target of peroxisome proliferator-activated receptor γ (PPARγ), a key transcription factor in adipogenesis. Four putative peroxisome proliferator response elements (PPREs) were identified in the miR-143 promoter region. Using chromatin immune-precipitation, we observed that PPARγ was bound with two PPRE regions of the miR-143 promoter in 3T3-L1 adipocytes. A luciferase reporter assay showed that the PPRE1 region (-1330/-1309) of the miR-143 promoter played an important role in PPARγ transcriptional activation. In addition, we determined that G-protein coupled receptor 120 (GPR 120), which functions as an omega 3 fatty acid receptor, affected miR-143 expression in adipocytes. GPR120 silencing in adipocytes inhibited the expression of PPARγ and miR-143, whereas GPR120 overexpression led to increased expressions of PPARγ and miR-143. Silencing of PPARγ inhibited the induction of miR-143 by GPR-120. These results suggested that a PPARγ-mediated GPR120 signaling pathway promotes transcriptional activation of miR-143 in adipocytes.