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Ursolic acid improves lipid and glucose metabolism in high‐fat‐fed C57BL/6J mice by activating peroxisome proliferator‐activated receptor alpha and hepatic autophagy
Author(s) -
Jia Yaoyao,
Kim Seyoung,
Kim Jiyoung,
Kim Bobae,
Wu Chunyan,
Lee Ji Hae,
Jun Heejin,
Kim Nahyun,
Lee Dongho,
Lee SungJoon
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400399
Subject(s) - endocrinology , lipogenesis , medicine , adiponectin , lipid metabolism , peroxisome proliferator activated receptor , peroxisome , chemistry , autophagy , adipose tissue , beta oxidation , triglyceride , fatty acid metabolism , biology , cholesterol , receptor , metabolism , insulin resistance , biochemistry , insulin , apoptosis
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.