Prostaglandin D 2 enhances lipid accumulation through suppression of lipolysis via DP2 (CRTH2) receptors in adipocytes

Biochem Biophys Res Commun. 2017 Aug 19;490(2):393-399. doi: 10.1016/j.bbrc.2017.06.053. Epub 2017 Jun 13.

Abstract

Prostaglandin (PG) D2 enhanced lipid accumulation in adipocytes. However, its molecular mechanism remains unclear. In this study, we investigated the regulatory mechanisms of PGD2-elevated lipid accumulation in mouse adipocytic 3T3-L1 cells. The Gi-coupled DP2 (CRTH2) receptors (DP2R), one of the two-types of PGD2 receptors were dominantly expressed in adipocytes. A DP2R antagonist, CAY10595, but not DP1 receptor antagonist, BWA868C cleared the PGD2-elevated intracellular triglyceride level. While, a DP2R agonist, 15R-15-methyl PGD2 (15R) increased the mRNA levels of the adipogenic and lipogenic genes, and decreased the glycerol release level. In addition, the forskolin-mediated increase of cAMP-dependent protein kinase A (PKA) activity and phosphorylation of hormone-sensitive lipase (HSL) was repressed by the co-treatment with 15R. Moreover, the lipolysis was enhanced in the adipocyte-differentiated DP2R gene-knockout mouse embryonic fibroblasts. These results indicate that PGD2 suppressed the lipolysis by repression of the cAMP-PKA-HSL axis through DP2R in adipocytes.

Keywords: Adipocyte; DP2 (CRTH2) receptor; Lipolysis; PGD(2).

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Gene Knockout Techniques
  • Lipolysis*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Prostaglandin D2 / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Prostaglandin / genetics
  • Receptors, Prostaglandin / metabolism*
  • Signal Transduction

Substances

  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Cyclic AMP-Dependent Protein Kinases
  • Prostaglandin D2
  • prostaglandin D2 receptor