title: Docosahexaenoic acid prevents trans-10, cis-12-conjugated linoleic acid-induced nonalcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation.
abstract: BACKGROUND
  Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented trans-10, cis-12-conjugated linoleic acid (CLA)-induced nonalcoholic fatty liver disease (NAFLD) and insulin resistance. The effective dose of DHA and mechanisms involved are poorly understood.
  
  
  METHODS
  We examined the ability of DHA (0.5% and 1.5%) to prevent increases in NAFLD and homeostatic model assessment of insulin resistance (HOMA-IR) induced by CLA (0.5%) when fed concomitantly for 4 weeks to C57BL/6N female mice. We also examined changes in expression of hepatic genes involved in fatty acid synthesis and oxidation.
  
  
  RESULTS
  CLA supplementation increased liver triglycerides (TG) and HOMA-IR by 221% and 547%, respectively, and decreased mass of different adipose depots by 65%-90% when compared to those in the control group. When fed concomitantly, DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but it did not prevent loss in adipose tissue mass. In the CLA+0.5% DHA group, the liver TG did not differ from those in the control group, but circulating insulin and HOMA-IR were 285% and 264%, respectively. In the CLA+1.5% DHA group, liver TG were 54% lower than those in the control group, but circulating insulin concentration and HOMA-IR did not differ between these two groups. CLA increased the expression of hepatic genes involved in fatty acid synthesis and decreased the expression of genes involved in fatty acid oxidation, and 1.5% DHA prevented changes in the expression of hepatic genes caused by CLA.
  
  
  CONCLUSIONS
  Response of different tissues to CLA and DHA varied; CLA was more potent than DHA in altering depot fat and insulin concentrations.
authors.affiliation: Western Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture and Department of Nutrition, University of California Davis, Davis, CA 95616, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Fedor
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Adkins
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Mackey
authors.forename: Darshan S
authors.initials: DS
authors.lastname: Kelley
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005234:Fatty Liver / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D044243:Linoleic Acids, Conjugated; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D010084:Oxidation-Reduction; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: C094849:10,12-octadecadienoic acid; D001786:Blood Glucose; D007328:Insulin; D044243:Linoleic Acids, Conjugated; D014280:Triglycerides; D004281:Docosahexaenoic Acids