Ursolic acid improves lipid and glucose metabolism in high-fat-fed C57BL/6J mice by activating peroxisome proliferator-activated receptor alpha and hepatic autophagy

Yaoyao Jia, Seyoung Kim, Jiyoung Kim, Bobae Kim, Chunyan Wu, Ji Hae Lee, Hee jin Jun, Nahyun Kim, Dongho Lee, Sung-Joon Lee

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Scope: This study investigated metabolic effects of ursolic acid (UA), a peroxisome proliferation-activated receptor (PPAR)-α activator, in vivo. Methods and results: High-fat diet (HFD)-fed C57BL/6J mice were orally administered UA (50 or 200 mg/kg body weight) for 8 wk. UA reduced liver and adipose tissue mass, adipocyte size, and plasma leptin concentrations, plasma triglyceride and low-density-lipoprotein cholesterol concentrations, while it elevated the high-density-lipoprotein cholesterol and adiponectin concentrations significantly compared with controls. UA induced the expression of PPARα and its responsive genes involved in fatty acid uptake and β-oxidation in the livers, whereas genes involved in lipogenesis, including sterol regulatory element-binding proteins-1c, were downregulated. UA administration improved glucose tolerance and insulin sensitivity significantly compared with the HFD-fed control livers. UA administration also activated hepatic autophagy as assessed by the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II and other key proteins in the autophagy pathway. Conclusion: Our findings suggest that UA ameliorates lipid and glucose metabolism in HFD-fed mice primarily by the activation of PPARα and induction of the hepatic autophagy pathway. Thus, intake of UA in the diet or in an isolated form may ameliorate lipid and glucose metabolism.

Original languageEnglish
Pages (from-to)344-354
Number of pages11
JournalMolecular Nutrition and Food Research
Volume59
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

Keywords

  • Autophagy
  • Glucose metabolism
  • Lipid metabolism
  • PPARα
  • Ursolic acid

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

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