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Mol Nutr Food Res. 2015 Aug;59(8):1491-503. doi: 10.1002/mnfr.201400670. Epub 2015 May 28.

Ursolic acid increases energy expenditure through enhancing free fatty acid uptake and β-oxidation via an UCP3/AMPK-dependent pathway in skeletal muscle.

Chu X1, He X1, Shi Z1, Li C1, Guo F1, Li S1, Li Y1,2, Na L1, Sun C1,2.

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Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
Research Institute of Food, Nutrition and Health, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China.



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.


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.


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.


AMP-activated protein kinase; Fatty acid β-oxidation; Free fatty acid uptake; Uncoupling protein 3; Ursolic acid

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