Vitisin A-13-O-β-D-glucoside and Vitisin A from Iris lactea inhibit lipogenesis and promote lipolysis via the PKA/HSL pathway during adipogenic transdifferentiation of C2C12 cells

Eur J Pharmacol. 2023 Dec 5:960:176154. doi: 10.1016/j.ejphar.2023.176154. Epub 2023 Oct 24.

Abstract

Oligostilbenes are a group of natural products derived from the polymerization of stilbene monomers. Despite the demonstration of their activities in regulating lipid metabolism, the function of oligostilbenes in the adipogenic transdifferentiation of multipotent myoblast cells remains unknown. Hence, the five oligostilbenes from Iris lactea were tested for their regulatory effects on adipogenic transdifferentiation of C2C12 myoblast cells. As a result, it was shown that Vitisin A-13-O-β-D-glucoside (VitAOG), Vitisin A (VitA) and Hopeaphenol (Hop) can greatly inhibit the adipogenic transdifferentiation of C2C12 cells by reducing lipid accumulation and downregulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein beta (C/EBPβ) and fatty acid binding proteins 4 (FABP4). In contrast, Vitisin D (VitD) and Isohopeaphenol (Isohop) promote adipogenic transdifferentiation of C2C12 cells by increasing lipid accumulation and upregulating the expression of adipogenesis and lipogenesis markers. Further research found that the lipolytic protein levels of adipocyte triglyceride lipase (ATGL) and phosphorylation of hormone-sensitive lipase (HSL) were elevated by VitAOG and VitA. Additionally, VitAOG and VitA maintain lipid homeostasis by improving mitochondrial function. Taken together, our study reveals an effect of oligostilbenes on lipid metabolism in C2C12 cells, and VitAOG and VitA can be regarded as potential candidates for the treatment of obesity and other disorders of lipid metabolism.

Keywords: Adipogenic transdifferentiation; C2C12 cells; Lipid metabolism; Lipolysis; Oligostilbenes.

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis*
  • Animals
  • Cell Transdifferentiation
  • Glucosides / pharmacology
  • Iris Plant* / metabolism
  • Lipids
  • Lipogenesis
  • Lipolysis
  • Mice
  • PPAR gamma / metabolism
  • Sterol Esterase / metabolism

Substances

  • vitisin A
  • Sterol Esterase
  • Glucosides
  • Lipids
  • PPAR gamma