3,3′-Diindolylmethane Suppresses Adipogenesis Using AMPK α -Dependent Mechanism in 3T3-L1 Adipocytes and Caenorhabditis elegans

Abstract

3,3′-diindolylmethane is a major in vivo metabolite of indole-3-carbinol, a bioactive compound found in cruciferous vegetables. Although 3,3′-diindolylmethane has been implicated to possess antitumorigenic and anti-inflammatory properties, the effect of 3,3′-diindolylmethane on adipogenesis has not been explored previously. Thus, the present study was conducted to determine if 3,3′-diindolylmethane affects adipogenesis using 3T3-L1 adipocytes and Caenorhabditis elegans. Treatment of 3,3′-diindolylmethane significantly reduced fat accumulation without affecting viability in 3T3-L1 adipocytes. 3,3′-diindolylmethane suppressed expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), fatty acid binding protein 4 (FABP4), and perilipin. In addition, 3,3′-diindolylmethane activated AMP-activated protein kinase α (AMPKα), which subsequently inactivated acetyl CoA carboxylase (ACC), resulting in reduced fat accumulation. These observations were further confirmed in C. elegans as treatment with 3,3′-diindolylmethane significantly reduced body fat accumulation, which was partly associated with aak-1, but not aak-2, orthologs of AMPKα catalytic subunits α1 and α2, respectively. The current results demonstrate that 3,3′-diindolylmethane, a biologically active metabolite of indole-3-carbinol, may prevent adipogenesis through the AMPKα-dependent pathway.