Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice

详细信息    查看全文

• 作者：Martin Rossmeisl ; Dasa Medrikova ; Evert M. van Schothorst ; Jana Pavlisova ; Ondrej Kuda ; Michal Hensler ; Kristina Bardova ; Pavel Flachs ; Barbora Stankova ; Marek Vecka ; Eva Tvrzicka ; Ales Zak ; Jaap Keijer ; Jan Kopecky
• 关键词：cHF ; corn oil-based high-fat diet ; Chow ; standard low-fat diet ; CLS ; crown-like structures ; DHA ; docosahexaenoic acid ; EPA ; eicosapentaenoic acid ; FA ; fatty acids ; FDR ; false discovery rate ; GEO ; Gene Expression Omnibus ; GSEA ; Gene Set Enrichment Analysis ; HDL-C ; high-density lipoprotein cholesterol ; HMW ; high molecular weight ; HOMA ; homeostasis model assessment ; LA ; linoleic acid ; NAFLD ; non-alcoholic fatty liver disease ; NEFA ; non-esterified fatty acids ; omega-3 ; long-chain n-3 polyunsaturated
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：February, 2014
• 年：2014
• 卷：1841
• 期：2
• 页码：267-278
• 全文大小：741 K

文摘

Non-alcoholic fatty liver disease (NAFLD) accompanies obesity and insulin resistance. Recent meta-analysis suggested omega-3 polyunsaturated fatty acids DHA and EPA to decrease liver fat in NAFLD patients. Anti-inflammatory, hypolipidemic, and insulin-sensitizing effects of DHA/EPA depend on their lipid form, with marine phospholipids showing better efficacy than fish oils. We characterized the mechanisms underlying beneficial effects of DHA/EPA phospholipids, alone or combined with an antidiabetic drug, on hepatosteatosis. C57BL/6N mice were fed for 7 weeks an obesogenic high-fat diet (cHF) or cHF-based interventions: (i) cHF supplemented with phosphatidylcholine-rich concentrate from herring (replacing 10% of dietary lipids; PC), (ii) cHF containing rosiglitazone (10 mg/kg diet; R), or (iii) PC + R. Metabolic analyses, hepatic gene expression and lipidome profiling were performed. Results showed that PC and PC + R prevented cHF-induced weight gain and glucose intolerance, while all interventions reduced abdominal fat and plasma triacylglycerols. PC and PC + R also lowered hepatic and plasma cholesterol and reduced hepatosteatosis. Microarray analysis revealed integrated down-regulation of hepatic lipogenic and cholesterol biosynthesis pathways by PC, while R-induced lipogenesis was fully counteracted in PC + R. Gene expression changes in PC and PC + R were associated with preferential enrichment of hepatic phosphatidylcholine and phosphatidylethanolamine fractions by DHA/EPA. The complex down-regulation of hepatic lipogenic and cholesterol biosynthesis genes and the antisteatotic effects were unique to DHA/EPA-containing phospholipids, since they were absent in mice fed soy-derived phosphatidylcholine. Thus, inhibition of lipid and cholesterol biosynthesis associated with potent antisteatotic effects in the liver in response to DHA/EPA-containing phospholipids support their use in NAFLD prevention and treatment.