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Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects.
Mol Cell Endocrinol. 2013 Aug 25; 376(1-2):70-80.MC

Abstract

Insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM), which is closely related to disorder of lipid metabolism. The study was designed to evaluate the effects of oleanolic acid (OA) on hepatic insulin resistance and underlying mechanisms in Lep(db)(/)(db) obese diabetic mice. db/db Mice were administered with OA (20mg/kg/day, i.p.) for two weeks. OA reduced body weight, liver weight, and fat weight, and protected liver morphology and function. OA decreased fasting blood glucose, improved glucose and insulin tolerance, enhanced insulin signaling and inhibited gluconeogenesis. In livers, mitochondrial biogenesis, ultrastructure and function were influenced, accompanied by increased cellular and mitochondrial ROS production. OA inhibited all these changes, in which process Nrf2-GCLc mediated stabilization of mitochondrial glutathione pool may be involved. Moreover, OA decreased serum triglyceride, total cholesterol, LDL, HDL, and free fatty acids, increased serum HDL, and reduced hepatic lipid accumulation. Furthermore, inflammatory condition in db/db mice was improved by OA, as evidenced by decreased level of IL-1 β, IL-6, and TNFα in circulation and in liver. The evidence suggests that OA improves hepatic insulin resistance through inhibition of mitochondrial ROS, hypolipidemic and anti-inflammatory effects. The effectiveness of OA leads to interesting therapeutic perspectives.

Authors+Show Affiliations

Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23791844

Citation

Wang, Xin, et al. "Oleanolic Acid Improves Hepatic Insulin Resistance Via Antioxidant, Hypolipidemic and Anti-inflammatory Effects." Molecular and Cellular Endocrinology, vol. 376, no. 1-2, 2013, pp. 70-80.
Wang X, Liu R, Zhang W, et al. Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects. Mol Cell Endocrinol. 2013;376(1-2):70-80.
Wang, X., Liu, R., Zhang, W., Zhang, X., Liao, N., Wang, Z., Li, W., Qin, X., & Hai, C. (2013). Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects. Molecular and Cellular Endocrinology, 376(1-2), 70-80. https://doi.org/10.1016/j.mce.2013.06.014
Wang X, et al. Oleanolic Acid Improves Hepatic Insulin Resistance Via Antioxidant, Hypolipidemic and Anti-inflammatory Effects. Mol Cell Endocrinol. 2013 Aug 25;376(1-2):70-80. PubMed PMID: 23791844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects. AU - Wang,Xin, AU - Liu,Rui, AU - Zhang,Wei, AU - Zhang,Xiaodi, AU - Liao,Nai, AU - Wang,Zhao, AU - Li,Wenli, AU - Qin,Xujun, AU - Hai,Chunxu, Y1 - 2013/06/18/ PY - 2013/02/25/received PY - 2013/05/06/revised PY - 2013/06/11/accepted PY - 2013/6/25/entrez PY - 2013/6/25/pubmed PY - 2014/2/12/medline KW - ALT KW - AMP-activated protein kinase KW - AMPK KW - AST KW - AUC KW - Akt KW - DCF KW - DHE KW - Dyslipidemia KW - FBG KW - FFAs KW - G6P KW - GCL KW - GCLc KW - GSH KW - GSSG KW - Glucose-6-phosphatase KW - HDL KW - HDL-cholesterol KW - Hepatic insulin resistance KW - IL-1β KW - IL-6 KW - IPGTT KW - IPITT KW - Inflammation KW - LDL KW - LDL-cholesterol KW - MMP KW - Nrf2 KW - OA KW - Oleanolic acid KW - PEPCK KW - PGC-1α KW - ROS KW - Reactive oxygen species KW - Rho123 KW - Rhodamine 123 KW - T2DM KW - TBARS KW - TC KW - TEM KW - TG KW - TNFα KW - TZDs KW - area under the curve KW - aspartate aminotransferase KW - dichlorodihydrofluorescein diacetate KW - dihydroethidium KW - fasting blood glucose KW - free fatty acids KW - glutathione KW - glutathione (oxidized form) KW - glutathione cysteine ligase catalytic subunit KW - interleukin-1β KW - interleukin-6 KW - intraperitoneal glucose tolerance test KW - intraperitoneal insulin tolerance test KW - mitochondrial membrane potential KW - nuclear factor erythroid 2 p45-related factor 2 KW - oleanolic acid KW - peroxisome proliferator-activated receptor-γ coactivator KW - phosphoenolpyruvate carboxykinase KW - protein kinase B KW - reactive oxygen species KW - serum alanine aminotransferase KW - thiazolidinediones KW - thiobarbituric acid reactive substances KW - total cholesterol KW - transmission electron microscopy KW - triglyceride KW - tumor necrosis factor α KW - type 2 diabetes mellitus KW - γ-Glutamylcysteine ligase SP - 70 EP - 80 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 376 IS - 1-2 N2 - Insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM), which is closely related to disorder of lipid metabolism. The study was designed to evaluate the effects of oleanolic acid (OA) on hepatic insulin resistance and underlying mechanisms in Lep(db)(/)(db) obese diabetic mice. db/db Mice were administered with OA (20mg/kg/day, i.p.) for two weeks. OA reduced body weight, liver weight, and fat weight, and protected liver morphology and function. OA decreased fasting blood glucose, improved glucose and insulin tolerance, enhanced insulin signaling and inhibited gluconeogenesis. In livers, mitochondrial biogenesis, ultrastructure and function were influenced, accompanied by increased cellular and mitochondrial ROS production. OA inhibited all these changes, in which process Nrf2-GCLc mediated stabilization of mitochondrial glutathione pool may be involved. Moreover, OA decreased serum triglyceride, total cholesterol, LDL, HDL, and free fatty acids, increased serum HDL, and reduced hepatic lipid accumulation. Furthermore, inflammatory condition in db/db mice was improved by OA, as evidenced by decreased level of IL-1 β, IL-6, and TNFα in circulation and in liver. The evidence suggests that OA improves hepatic insulin resistance through inhibition of mitochondrial ROS, hypolipidemic and anti-inflammatory effects. The effectiveness of OA leads to interesting therapeutic perspectives. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/23791844/Oleanolic_acid_improves_hepatic_insulin_resistance_via_antioxidant_hypolipidemic_and_anti_inflammatory_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(13)00252-9 DB - PRIME DP - Unbound Medicine ER -