title: Ursolic acid increases energy expenditure through enhancing free fatty acid uptake and β-oxidation via an UCP3/AMPK-dependent pathway in skeletal muscle.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Fuchuan
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Na
authors.affiliation: 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.
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D065567:Absorption, Physiological; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D007473:Ion Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism; D034622:RNA Interference; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems; D013047:Specific Pathogen-Free Organisms; D014315:Triterpenes / Q000627:therapeutic use*; D000071247:Uncoupling Protein 3; D000097245:Ursolic Acid
chemical_list: D055372:AMP-Activated Protein Kinases; D019440:Anti-Obesity Agents; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; D014315:Triterpenes; D000071247:Uncoupling Protein 3; D000097245:Ursolic Acid; C000604393:Ucp3 protein, mouse; C000604394:Ucp3 protein, rat; C568305:Prkaa1 protein, rat
keywords: AMP-activated protein kinase; Fatty acid β-oxidation; Free fatty acid uptake; Uncoupling protein 3; Ursolic acid