[Statin reduced triglyceride level via activating peroxisome proliferator activated receptor α and upregulating apolipoprotein A5 in hypertriglyceridemic rats]

Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Sep;38(9):809-13.
[Article in Chinese]

Abstract

Objective: to explore the potential role of apolipoprotein A5 (apoA5) on the hypertriglyceridemia (HTG)-lowering effects of statin.

Methods: twenty-four Sprague-Dawley rats were randomized into 3 groups: (1) control group (n = 8), with no special treatment; (2) HTG group (n = 8), treated with 10% fructose water for 6 weeks; (3) statin group (n = 8), treated with 10% fructose water for 2 weeks and cotreated with atorvastatin 10 mg×kg(-1)×d(-1) for another 4 weeks. Body weight, fasting plasma lipids and the hepatic expressions of apoA5 and peroxisome proliferator activated receptor (PPAR)α were determined. In separate in vitro experiments, we tested the effects of atorvastatin on TG and the expressions of apoA5 and PPARα in HepG2 cells.

Results: (1) at 6 weeks, plasma TG was higher in rats in HTG group than in controls, which was significantly reduced in statin group (both P < 0.05). (2) Rat hepatic apoA5 expression in HTG group was significantly lower than in control group and was significantly higher in statin group than in HTG group (both P < 0.05). (3) Similarly, rat PPARα mRNA expression in HTG group was lower than in control group and was higher in statin group than in HTG group (both P < 0.05). (4) Statin significantly upregulated the expressions of apoA5 and PPARα and decreased TG in HepG2 cells. The above effects induced by statin was blocked in the presence of PPARα inhibitor.

Conclusions: upregulation of apoA5 expression contributes to TG lowering effect of statin via PPARα signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-V
  • Apolipoproteins / blood*
  • Atorvastatin
  • Down-Regulation
  • Hep G2 Cells
  • Heptanoic Acids / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypertriglyceridemia / metabolism*
  • Male
  • PPAR alpha / metabolism*
  • Pyrroles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / blood*
  • Up-Regulation

Substances

  • Apoa5 protein, rat
  • Apolipoprotein A-V
  • Apolipoproteins
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PPAR alpha
  • Pyrroles
  • Triglycerides
  • Atorvastatin