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Ursolic acid increases energy expenditure through enhancing free fatty acid uptake and β‐oxidation via an UCP3/AMPK‐dependent pathway in skeletal muscle
Author(s) -
Chu Xia,
He Xuan,
Shi Zhiping,
Li Chunjuan,
Guo Fuchuan,
Li Songtao,
Li Ying,
Na Lixin,
Sun Changhao
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.201400670
Subject(s) - ampk , skeletal muscle , beta oxidation , endocrinology , medicine , ucp3 , chemistry , ursolic acid , amp activated protein kinase , lipogenesis , fatty acid , triglyceride , adenosine monophosphate , protein kinase a , biochemistry , adenosine , adipose tissue , brown adipose tissue , uncoupling protein , biology , kinase , chromatography , cholesterol
Scope Ursolic acid (UA) is a triterpenoid compound with multifold biological functions. Our previous studies have reported that UA protects against high‐fat diet‐induced obesity and improves insulin resistance (IR). However, the potential mechanisms are still undefined. Free fatty acid (FFA) metabolism in skeletal muscle plays a central role in obesity and IR. Therefore, in this study, we investigated the effect and the potential mechanisms of UA on skeletal muscle FFA metabolism. Methods and results In diet‐induced obese rats, 0.5% UA supplementation for 6 weeks markedly reduced body weight, increased energy expenditure, decreased FFA level in serum and skeletal muscle and triglyceride content in skeletal muscle. In vitro, the data provided directly evidence that UA significantly increased fluorescently labeled FFA uptake and 3 H‐labeled palmitic acid β‐oxidation. UA‐activated AMP‐activated protein kinase (AMPK) and downstream targets were involved in the increase of FFA catabolism. Moreover, upregulated uncoupling protein 3 (UCP3) by UA contributed to AMPK activation via elevating adenosine monophosphate/adenosine triphosphate ratio. Conclusion UA increases FFA burning through enhancing skeletal muscle FFA uptake and β‐oxidation via an UCP3/AMPK‐dependent pathway, which provides a novel perspective on the biological function of UA against obesity and IR.