Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway

Biochem Biophys Res Commun. 2016 Sep 23;478(3):1173-8. doi: 10.1016/j.bbrc.2016.08.087. Epub 2016 Aug 17.


Introduction: Apolipoprotein A5 (apoA5) is a key regulator of triglyceride (TG) metabolism. This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions.

Methods: Two obese mouse models, including high-fat diet-induced obese mice and ob/ob obese mice, were adopted. The effects of low- and high-dose metformin were determined on plasma and hepatic TG and apoA5 of these obese mice. Besides, the effects of metformin on TG and apoA5 were also detected in mouse and human hepatocytes in vitro.

Results: (1) Plasma apoA5 levels in the obese mice were markedly elevated and positively correlated with TG. Hepatic TG contents and apoA5 expressions were also remarkably increased in the obese mice. (2) Metformin dose-dependently decreased hepatic and plasma TG and apoA5 in the obese mice. Similarly, metformin dose-dependently reduced cellular TG contents and apoA5 expressions in hepatocytes in vitro. Compared to APOA5 knock-down (KD), metformin plus APOA5 KD resulted in more TG reduction of hepatocytes.

Conclusion: Increased hepatic and plasma apoA5 could be a result of obesity-associated hypertriglyceridemia, and metformin displays hypotriglyceridemic effects on obese mice partly via the apoA5 pathway.

Keywords: Apolipoprotein A5; Metformin; Obesity; Triglyceride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-V / metabolism*
  • Body Weight / drug effects
  • Hep G2 Cells
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / drug therapy*
  • Hypertriglyceridemia / metabolism*
  • Male
  • Metformin / pharmacology
  • Metformin / therapeutic use*
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / blood
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism*
  • Triglycerides / blood


  • Apolipoprotein A-V
  • Triglycerides
  • Metformin