title: Ergostatrien-3β-ol from Antrodia camphorata inhibits diabetes and hyperlipidemia in high-fat-diet treated mice via regulation of hepatic related genes, glucose transporter 4, and AMP-activated protein kinase phosphorylation.
abstract: This study was designed to explore the effects and mechanism of ergostatrien-3β-ol (EK100) from the submerged whole broth of Antrodia camphorata on diabetes and dyslipidemia in high fat diet (HFD)-fed mice for 12 weeks. The C57BL/6J mouse fed with a high fat diet (HFD) could induce insulin resistance and hyperlipidemia. After 8 week of induction, mice were receiving EK100 (at three dosages) or fenofibrate (Feno) or rosiglitazone (Rosi) or vehicle by oral gavage 4 weeks afterward. HFD-fed mice display increased blood glucose, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), insulin, and leptin levels. These blood markers were significantly lower in EK100-treated mice, and finally ameliorated insulin resistance. EK100 treatment exhibited reduced hepatic ballooning degeneration and size of visceral adipocytes. Glucose transporter 4 (GLUT4) proteins and phosphorylation of Akt in skeletal muscle were significantly increased in EK100- and Rosi-treated mice. EK100, Feno, and Rosi treatment led to significant increases in phosphorylation of AMP-activated protein kinase (phospho-AMPK) protein in both skeletal muscle and liver. Moreover, EK100 caused a decrease in hepatic expressions of phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase), and decreased glucose production. EK100 lowered blood TG level by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein-1c (SREBP-1c) but increasing expression of peroxisome proliferator activated receptor α (PPARα). Moreover, EK100-treated mice reduced blood TC levels by decreased hepatic expressions of SREBP2, which plays a major role in the regulation of cholesterol synthesis. EK100 increased high-density lipoprotein cholesterol (HDL-C) concentrations by increasing expressions of apolipoprotein A-I (apo A-I) in liver tissue. Our findings manifest that EK100 may have therapeutic potential in treating type 2 diabetes associated with hyperlipidemia in HFD-fed mice by regulation of GLUT4, PEPCK, G6 Pase, SREBP1c, SREBP2, apo A-I, and AMPK phosphorylation.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University , Taichung City 40402, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.forename: Cheng-Hsiu
authors.initials: CH
authors.lastname: Lin
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Shih
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055491:Antrodia / Q000737:chemistry*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004875:Ergosterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D051275:Glucose Transporter Type 4; D014280:Triglycerides; C000600922:ergostatrien-3-ol; D055372:AMP-Activated Protein Kinases; D004875:Ergosterol
keywords: AMP-activated protein kinase phosphorylation; Antrodia camphorata; diabetes; glucose transporter 4; hypercholesterolemia; hyperlipidemia