Inhibitory effect of sinigrin on adipocyte differentiation in 3T3-L1 cells: Involvement of AMPK and MAPK pathways

Biomed Pharmacother. 2018 Jun:102:670-680. doi: 10.1016/j.biopha.2018.03.124. Epub 2018 Apr 5.

Abstract

Adipocyte differentiation is a critical adaptive response to nutritional overload and affects the metabolic outcome of obesity. Sinigrin (2-propenyl glucosinolate) is a glucosinolate belong to the glucoside contained in broccoli, brussels sprouts, and black mustard seeds. We investigated the effects of sinigrin on adipogenesis in 3T3-L1 preadipocytes and its underlying mechanisms. Sinigrin remarkably inhibited the accumulation of lipid droplets and adipogenesis by downregulating the expression of CCAAT-enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), leptin and aP2. Sinigrin arrested cells in the G0/G1 phase of the cell cycle and increased the expression of p21 and p27. CDK2 expression was suppressed by sinigirn in MDI-induced adipocytes. Sinigrin increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and acetyl-CoA carboxylase (ACC) in the early stage of adipocyte differentiation, suggesting that sinigrin has anti-adipogenic effects through AMPK, MAPK and ACC activation. Sinigrin also inhibited the production of pro-inflammatory cytokines including tumor necrosis factor -alpha (TNF-α) and interleukin (IL)-6, IL-1β and IL-18. Taken together, these data suggest that sinigrin inhibits early-stage adipogenesis of 3T3-L1 adipocytes through the AMPK and MAPK signaling pathways.

Keywords: 2-Propenyl glucosinolate; 3T3-L1 cells; AMPK; Adipocytes; Adipogenesis.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / enzymology*
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Animals
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Clone Cells
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Glucosinolates / pharmacology*
  • Inflammation / pathology
  • Lipid Metabolism / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mitosis / drug effects
  • PPAR gamma / metabolism

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Cytokines
  • Glucosinolates
  • PPAR gamma
  • sinigrin
  • AMP-Activated Protein Kinases