Details

Autor(en) / Beteiligte

• Rossmeisl, Martin
• Medrikova, Dasa
• van Schothorst, Evert M.
• Pavlisova, Jana
• Kuda, Ondrej
• Hensler, Michal
• Bardova, Kristina
• Flachs, Pavel
• Stankova, Barbora
• Vecka, Marek
• Tvrzicka, Eva
• Zak, Ales
• Keijer, Jaap
• Kopecky, Jan

Titel

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

Ist Teil von

• Biochimica et biophysica acta, 2014-02, Vol.1841 (2), p.267-278

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 7weeks 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 (10mg/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. •Omega-3 fatty acids (omega-3) reduce obesity and hepatosteatosis in rodents.•Omega-3-containing marine phospholipids (PL) show better efficacy than fish oils.•Omega-3 PL reduce hepatosteatosis by inhibiting lipogenesis/cholesterol biosynthesis.•Soy-derived PL devoid of omega-3 are ineffective.•The complex effect of omega-3 PL suggests their potential use in NAFLD treatment.