Rev-erbα Inhibits Proliferation and Promotes Apoptosis of Preadipocytes through the Agonist GSK4112

Int J Mol Sci. 2019 Sep 12;20(18):4524. doi: 10.3390/ijms20184524.

Abstract

Proliferation and apoptosis are important physiological processes of preadipocytes. Rev-erbα is a circadian clock gene, and its activity contributes to several physiological processes in various cells. Previous studies demonstrated that Rev-erbα promotes preadipocyte differentiation, but a role of Rev-erbα on preadipocyte proliferation and apoptosis has not been demonstrated. GSK4112 is often used as an agonist of Rev-erbα. In this study, we used GSK4112 to explore the effects of Rev-erbα on preadipocyte proliferation and apoptosis by RT-qPCR, Western blot, Cell Counting Kit-8 (CCK8) measurement, 5-Ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/PI staining, and flow cytometry. These results revealed that GSK4112 inhibited the viability of 3T3-L1 preadipocytes and decreased cell numbers. There was also decreased expression of the proliferation-related gene Cyclin D and the canonical Wingless-type (Wnt) signaling effect factor β-catenin. Furthermore, palmitate (PA)-inducing cell apoptosis was promoted. Overall, these results reveal that Rev-erbα plays a role in proliferation and palmitate (PA)-inducing apoptosis of 3T3-L1 preadipocytes, and thus may be a new molecular target in efforts to prevent and treat obesity and related disease.

Keywords: GSK4112; Rev-erbα; apoptosis; proliferation; β-catenin.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Animals
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Mice
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / agonists*
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism
  • Thiophenes / pharmacology*

Substances

  • GSK4112
  • Nr1d1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Thiophenes
  • Glycine