title: Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver.
abstract: Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation.
authors.affiliation: Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China.
authors.forename: Xiaomang
authors.initials: X
authors.lastname: Xing
authors.affiliation: Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Li
authors.affiliation: Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China.
authors.forename: Dilong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Koei Kogyo Co., Ltd., Tokyo, 101-0063 Japan.
authors.forename: Ritsu
authors.initials: R
authors.lastname: Chonan
authors.affiliation: Pharmafood Institute, Kyoto, 602-8136 Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Yamahara
authors.affiliation: Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 China. Electronic address: wangjianwei1968@gmail.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000 Australia. Electronic address: yuhao@sitcm.edu.au.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D005234:Fatty Liver / Q000188:drug therapy*; D005632:Fructose / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D051780:Sterol Regulatory Element Binding Protein 1; D044004:Xanthones; C013592:mangiferin; D005632:Fructose; C494883:Dgat1 protein, rat; C522579:Dgat2 protein, rat; D051048:Diacylglycerol O-Acyltransferase
keywords: DGAT-2; Fructose; Liver; Mangiferin; SHR; Steatosis