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Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease
Journal article   Open access   Peer reviewed

Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease

Steven D Kunkel, Christopher J Elmore, Kale S Bongers, Scott M Ebert, Daniel K Fox, Michael C Dyle, Steven A Bullard and Christopher M Adams
PloS one, Vol.7(6), pp.e39332-e39332
2012
DOI: 10.1371/journal.pone.0039332
PMCID: PMC3379974
PMID: 22745735
url
https://doi.org/10.1371/journal.pone.0039332View
Published (Version of record) Open Access

Abstract

Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.
Glucose Intolerance - drug therapy Animals Obesity - drug therapy Mice, Inbred C57BL Muscle, Skeletal - drug effects Triterpenes - therapeutic use Male Muscle, Skeletal - metabolism Adipose Tissue, Brown - drug effects Adipose Tissue, Brown - metabolism Mice Fatty Liver - drug therapy

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