title: Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice.
abstract: BACKGROUND
  Low hepatic content of n-3 PUFA has been associated with NAFLD in humans. Whether this is associated with reduced dietary intake or increased turnover of these FA is not clear. We have here investigated the effects of dietary fat quality on hepatic lipid storage and transcriptomics over time.
  
  
  OBJECTIVE
  To investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and liver transcriptomics.
  
  
  RESULTS
  Male C57BL/6J mice were fed control, HFD-eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) or HFD-corn oil diet for 8 or 12 weeks. Body weight, body composition, plasma and hepatic triglyceride contents were measured. Hepatic transcriptomes were analysed by microarray followed by gene-set enrichment analyses. At 8 weeks, the HFD-corn oil mice had higher body weight and adipose depot mass than the HFD-EPA/DHA but there were no differences at 12 weeks. Hepatic triglyceride content was lower in HFD-EPA/DHA fed compared with the HFD-corn oil fed mice at both time-points. Enrichment analyses of the hepatic transcriptomes showed that lipid/fatty acid biosynthesis; transport and homeostasis were lower in the HFD-EPA/DHA fed compared with the HFD-corn oil fed mice. Genes encoding proteins associated to cytoplasmic lipid droplets were expressed at higher levels in livers from the HFD-corn oil compared to HFD-EPA/DHA mice.
  
  
  CONCLUSIONS
  Dietary EPA and DHA counteracted development of HFD-induced fatty liver. The liver transcriptome data implicate that the quality of dietary fat could modulate Ppar-related gene expression that in turn affects hepatic lipid storage and maintenance of metabolic health.
authors.affiliation: Divisions of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296, Gothenburg, Sweden. soni@chalmers.se.
authors.forename: Nikul K
authors.initials: NK
authors.lastname: Soni
authors.affiliation: The division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296, Gothenburg, Sweden. intawat@chalmers.se.|Present address: Comparative Genomics Group, Biosciences division, Oak Ridge National Library, Oak Ridge, TN, 37831, USA. intawat@chalmers.se.
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.affiliation: Divisions of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296, Gothenburg, Sweden. ann-sofie.sandberg@chalmers.se.
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Sandberg
authors.affiliation: Divisions of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296, Gothenburg, Sweden. brittg@chalmers.se.
authors.forename: Britt G
authors.initials: BG
authors.lastname: Gabrielsson
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D059305:Diet, High-Fat; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014280:Triglycerides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid