title: Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK.
abstract: Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Yucun
authors.initials: Y
authors.lastname: Niu
authors.forename: Songtao
authors.initials: S
authors.lastname: Li
authors.forename: Lixin
authors.initials: L
authors.lastname: Na
authors.forename: Rennan
authors.initials: R
authors.lastname: Feng
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008660:Metabolism / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D014280:Triglycerides; D044004:Xanthones; C013592:mangiferin; D000263:Adenylate Kinase