HM-chromanone inhibits adipogenesis by regulating adipogenic transcription factors and AMPK in 3T3-L1 adipocytes

Abstract

Portulaca oleracea L. is used as a folk medicine in many countries because of its wide range of pharmacological effects. HM-chromanone, isolated from P. oleracea using bioassay-guided fractionation and HPLC, belongs to the homoisoflavonoid group and has been shown to exert several biological effects. In this study, we evaluated whether HM-chromanone inhibits adipogenesis by regulating adipogenic transcription factors in 3T3-L1 adipocytes. The results showed that HM-chromanone suppresses adipocyte differentiation and adipogenesis in a dose-dependent manner in 3T3-L1 adipocytes. The HM-chromanone-treated adipocytes exhibited lower triglyceride accumulation and leptin secretion, and higher glycerol and adiponectin secretion than the control adipocytes. Microscopic observation using oil red O staining revealed a dose-dependent reduction in the number of lipid droplets in the HM-chromanone-treated adipocytes compared to the control group. HM-chromanone significantly down-regulated the protein expression of major adipogenic transcription factors sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα) and markedly inhibited several key adipogenic enzymes including fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were both more activated in the HM-chromanone-treated adipocytes than in the control adipocytes. HM-chromanone also promoted the phosphorylation of 5' Adenosine monophosphate-activated protein kinase (AMPK), which inhibits adipogenesis through the regulation of adipogenic transcription factors. These results suggest that HM-chromanone may be an effective anti-adipogenesis agent that functions via the suppression of adipogenic transcription factors and the activation of AMPK.

Keywords: 3T3-L1 adipocytes; AMPK; Anti-adipogenesis; HM-chromanone; Homoisoflavonoid; Obesity.