Dibenzoylmethane Suppresses Lipid Accumulation and Reactive Oxygen Species Production through Regulation of Nuclear Factor (Erythroid-Derived 2)-Like 2 and Insulin Signaling in Adipocytes

Biol Pharm Bull. 2018;41(5):680-689. doi: 10.1248/bpb.b17-00837.

Abstract

The aim of this study was to investigate the effects of dibenzoylmethane (1,3-diphenyl-1,3-propanedione, DBM) from licorice roots on lipid accumulation and reactive oxygen species (ROS) production in 3T3-L1 cells. DBM effectively inhibited lipid accumulation during adipogenesis, and its inhibitory effect was shown to be due to the down-regulation of adipogenic factors such as CCAAT-enhancer-binding protein-α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid-binding protein 4 (FABP4). DBM was observed to exert its inhibitory effect on lipid accumulation in the early adipogenic stage (days 0-2) by regulating early adipogenic factors including CCAAT-enhancer-binding protein-β (C/EBPβ) and Krueppel-like factor (KLF) 2. DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.

Keywords: 3T3-L1; dibenzoylmethane; insulin signaling; lipid accumulation; nuclear factor (erythroid-derived 2)-like 2; reactive oxygen species.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adiponectin / genetics
  • Animals
  • Catalase / genetics
  • Cell Differentiation
  • Cell Survival / drug effects
  • Chalcones / pharmacology*
  • Glutathione Peroxidase / genetics
  • Heme Oxygenase-1 / metabolism
  • Insulin / metabolism*
  • Lipid Metabolism / drug effects*
  • Membrane Proteins / metabolism
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Resistin / genetics
  • Signal Transduction
  • Superoxide Dismutase / genetics

Substances

  • Adiponectin
  • Adipoq protein, mouse
  • Chalcones
  • Insulin
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species
  • Resistin
  • Retn protein, mouse
  • dibenzoylmethane
  • Catalase
  • Glutathione Peroxidase
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Superoxide Dismutase