title: Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study.
abstract: Treatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (FAs) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial FA partitioning and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME trial (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy).
  
  
  
  Sixteen participants were randomised to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15-18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or ⩾2% post intervention).
  
  
  
  Nine participants were stratified to DHA⩾2% (eight randomised to EPA+DHA and one to placebo) and seven to the DHA<2% group (all placebo). Compared with individuals with erythrocyte <2% change in DHA abundance, those with ⩾2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of13C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05).
  
  
  
  The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment ⩾2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Hodson
authors.affiliation: Human Development and Health Academic Unit, Southampton, UK.
authors.forename: L
authors.initials: L
authors.lastname: Bhatia
authors.affiliation: Human Development and Health Academic Unit, Southampton, UK.|NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.
authors.forename: E
authors.initials: E
authors.lastname: Scorletti
authors.affiliation: Human Development and Health Academic Unit, Southampton, UK.|NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.
authors.forename: D E
authors.initials: DE
authors.lastname: Smith
authors.affiliation: Diabetes and Metabolic Medicine, Department of Nutritional Sciences, University of Surrey, Guildford, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: Jackson
authors.affiliation: Diabetes and Metabolic Medicine, Department of Nutritional Sciences, University of Surrey, Guildford, UK.
authors.forename: F
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.affiliation: Diabetes and Metabolic Medicine, Department of Nutritional Sciences, University of Surrey, Guildford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Umpleby
authors.affiliation: Human Development and Health Academic Unit, Southampton, UK.|NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Calder
authors.affiliation: Human Development and Health Academic Unit, Southampton, UK.|NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism; D010865:Pilot Projects; D000075082:Proof of Concept Study
chemical_list: D015415:Biomarkers; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D020155:3-Hydroxybutyric Acid