Therapeutic Role of Ursolic Acid on Ameliorating Hepatic Steatosis and Improving Metabolic Disorders in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Rats

• Published in: PloS one Vol. 9; no. 1; p. e86724
• Main Authors: Li, Songtao, Meng, Fanyu, Liao, Xilu, Wang, Yemei, Sun, Zongxiang, Guo, Fuchuan, Li, Xiaoxia, Meng, Man, Li, Ying, Sun, Changhao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.01.2014; Public Library of Science (PLoS)
• Subjects: Acid resistance; Acids; Animals; Biology; CD36 Antigens - genetics; CD36 Antigens - metabolism; Diabetes mellitus; Diacylglycerol O-Acyltransferase - genetics; Diacylglycerol O-Acyltransferase - metabolism; Diet; Diet, High-Fat; Dietary Fats - adverse effects; Disorders; Enzymes; Fatty liver; Fatty Liver - drug therapy; Fatty Liver - etiology; Fatty Liver - metabolism; Fatty Liver - pathology; Gene Expression; Health aspects; High fat diet; Insulin; Insulin Resistance; Laboratory animals; Lipase - genetics; Lipase - metabolism; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Male; Medicine; Metabolic disorders; Metabolism; mRNA; Non-alcoholic Fatty Liver Disease; Obesity; Obesity - drug therapy; Obesity - etiology; Obesity - metabolism; Obesity - pathology; Oxidation resistance; Oxidative stress; Peroxisome proliferator-activated receptors; Plants (botany); PPAR alpha - antagonists & inhibitors; PPAR alpha - genetics; PPAR alpha - metabolism; Rats; Rats, Sprague-Dawley; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Rodents; Steatosis; Triterpenes - pharmacology; Ursolic Acid
• DOI: 10.1371/journal.pone.0086724
• ISSN: 1932-6203

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.