title: Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.
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.
authors: Department of Internal Medicine, and Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors: Steven D
authors: SD
authors: Kunkel
authors: Christopher J
authors: CJ
authors: Elmore
authors: Kale S
authors: KS
authors: Bongers
authors: Scott M
authors: SM
authors: Ebert
authors: Daniel K
authors: DK
authors: Fox
authors: Michael C
authors: MC
authors: Dyle
authors: Steven A
authors: SA
authors: Bullard
authors: Christopher M
authors: CM
authors: Adams
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005234:Fatty Liver / Q000188:drug therapy*; D018149:Glucose Intolerance / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy*; D014315:Triterpenes / Q000627:therapeutic use*; D000097245:Ursolic Acid
chemical_list: D014315:Triterpenes; D000097245:Ursolic Acid