Dipeptidyl-peptidase-IV by cleaving neuropeptide Y induces lipid accumulation and PPAR-γ expression

Peptides. 2012 Sep;37(1):49-54. doi: 10.1016/j.peptides.2012.06.014. Epub 2012 Jul 20.

Abstract

We evaluated the effects of dipeptidyl peptidase-IV (DPPIV), and its inhibitor, vildagliptin, on adipogenesis and lipolysis in a pre-adipocyte murine cell line (3T3-L1). The exogenous rDPPIV increased lipid accumulation and PPAR-γ expression, whereas an inhibitor of DPPIV, the anti-diabetic drug vildagliptin, suppresses the stimulatory role of DPPIV on adipogenesis and lipid accumulation, but had no effect on lipolysis. NPY immunoneutralization or NPY Y(2) receptor blockage inhibited DPPIV stimulatory effects on lipid accumulation, collectively, indicating that DPPIV has an adipogenic effect through NPY cleavage and subsequent NPY Y(2) activation. Vildagliptin inhibits PPAR-γ expression and lipid accumulation without changing lipolysis, suggesting that this does not impair the ability of adipose tissue to store triglycerides inside lipid droplets. These data indicate that DPPIV and NPY interact on lipid metabolism to promote adipose tissue depot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adamantane / analogs & derivatives
  • Adamantane / pharmacology
  • Adipocytes / enzymology
  • Adipocytes / metabolism
  • Adipocytes / physiology
  • Animals
  • Cell Differentiation
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl Peptidase 4 / physiology*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Gene Expression
  • Insulin / pharmacology
  • Insulin / physiology
  • Lipid Metabolism*
  • Mice
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism*
  • Nitriles / pharmacology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Proteolysis
  • Pyrrolidines / pharmacology
  • Receptors, Neuropeptide Y / metabolism
  • Vildagliptin

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Insulin
  • Neuropeptide Y
  • Nitriles
  • PPAR gamma
  • Pyrrolidines
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • Dipeptidyl Peptidase 4
  • Vildagliptin
  • Adamantane