NYMC Faculty Publications

Rotenoisin A is a Novel Anti-Adipogenic Compound

DOI

10.1016/j.bmcl.2018.11.008

Journal Title

Bioorganic & Medicinal Chemistry Letters

First Page

89

Last Page

96

Document Type

Article

Publication Date

January 2019

Department

Environmental Health Science

Abstract

The purpose of this study was to investigate the mechanisms underlying the inhibitory effects of rotenoisin A on adipogenesis in 3T3-L1 preadipocytes. 3T3-L1 cells were treated with rotenoisin A for 8days after the induction of differentiation. Oil-red O staining showed that rotenoisin A significantly inhibited DMI-induced lipid accumulation and adipocyte differentiation. We found that rotenoisin A treatment of 3T3-L1 preadipocytes significantly reduced the mRNA and protein levels of the key adipocyte-specific transcription factors C/EBPbeta, C/EBPalpha, and PPARgamma and markedly inhibited the expression of fatty acid-binding protein (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Furthermore, we observed that rotenoisin A substantially increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated acetyl CoA carboxylase (ACC). However, co-treatment with Compound C, an AMPK inhibitor, reversed the rotenoisin A-induced inhibition of the expression of the adipogenic transcription factors C/EBPalpha and PPARgamma and decreased the levels of phosphorylated AMPK in differentiated 3T3-L1 cells. These results demonstrated that the anti-adipogenesis mechanism involves the down-regulation of critical adipogenic transcription factors, including C/EBPbeta, C/EBPalpha, and PPARgamma, through activation of the AMPK signaling pathway by rotenoisin A.

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