Transcriptomics,Genomics

Dataset Information

45

Marine omega-3 phospholipids suppress hepatic steatosis by a complex inhibition of biosynthetic pathways in dietary obese mice


ABSTRACT: Background & Aims: Non-alcoholic fatty liver disease accompanies obesity and is independently associated with cardiovascular disease. Omega-3 fatty acids, such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid, reduce the risk of cardiovascular disease due to their anti-inflammatory and hypolipidemic effects. Recent data suggested that metabolic effects of EPA/DHA as marine phospholipids could be stronger than triglycerides (fish oil). We characterised the mechanisms underlying beneficial effects of EPA/DHA phospholipids alone or in combination with antidiabetic drugs on hepatosteatosis in dietary obese mice. Methods: Male C57BL/6N mice were fed for 7 weeks a corn oil-based high-fat diet (cHF) or subjected to cHF-based interventions: (i) cHF with DHA/EPA as phosphatidylcholine-rich concentrate replacing ~10 % of dietary lipids (PC); ii) cHF with a low-dose of thiazolidinedione rosiglitazone (10 mg/kg diet), which retains some of the beneficial effects but also potentiates hepatic lipid accumulation (R); and iii) PC+R. Metabolic profiling together with hepatic gene expression and lipidomic analyses were performed. Results: PC and PC+R prevented weight gain and glucose intolerance induced by cHF, while all interventions reduced abdominal fat and plasma triglycerides. In contrast to R, PC and PC+R lowered hepatic and plasma cholesterol and eliminated hepatosteatosis. Hepatic microarray analysis primarily revealed a complex downregulation of lipogenic and cholesterol biosynthesis pathways by PC. Lipidomic analysis identified arachidonic acid, DHA and EPA in hepatic phosphatidylcholine and phosphatidylethanolamine fractions as the most important variables. Importantly, down-regulation of genes within these pathways was enlarged by phospholipid versus triglyceride forms of EPA/DHA in an independent experiment. Conclusions: Obesity-associated hepatosteatosis and hypercholesterolemia were ameliorated by marine phospholipids in association with a complex inhibition of biosynthetic pathways in liver. Stronger effects of phospholipids versus triglyceride form of EPA/DHA suggest their preferential use in the prevention and possible treatment of obesity-associated metabolic hepatic dysfunctions. Overall design: C57BL/6N wildtype male mice, aged 3 months and fed chow, received for 7 weeks a control corn oil-based high-fat diet (cHF), or one of the cHF supplementations: 1) ~7 % of dietary lipids was replaced by the EPA and DHA concentrate in the form of omega-3 phospholipids rich in phosphatidylcholine (PC); 2) low dose rosiglitazone (R); and 3) both PC and rosiglitazone (PC+R). After sacrification, liver was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 4x44K microarrays. Based on raw MA-plots, we excluded one HF and one R array sample before normalization.

INSTRUMENT(S): Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version)

SUBMITTER: Evert M. van Schothorst  

PROVIDER: GSE45235 | GEO | 2014-07-30

SECONDARY ACCESSION(S): PRJNA193303

REPOSITORIES: GEO

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

Rossmeisl Martin M   Medrikova Dasa D   van Schothorst Evert M EM   Pavlisova Jana J   Kuda Ondrej O   Hensler Michal M   Bardova Kristina K   Flachs Pavel P   Stankova Barbora B   Vecka Marek M   Tvrzicka Eva E   Zak Ales A   Keijer Jaap J   Kopecky Jan J  

Biochimica et biophysica acta 20140201 2


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. Antiinflammatory, hypolipidemic, and insulin-sensitizing effects ofDHA/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 antidiabeti  ...[more]

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