title: Effect of DHA-rich fish oil on PPARγ target genes related to lipid metabolism in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial.
abstract: BACKGROUND
  The beneficial effects of omega-3 polyunsaturated fatty acids on lipid levels are well documented. However, the related molecular mechanisms are widely unknown. Omega-3 polyunsaturated fatty acids are natural ligand for peroxisome proliferator-activated receptor γ (PPARγ).
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effect of docosahexaenoic acid (DHA)-rich fish oil supplementation on modulation of some PPARγ-responsive genes related to lipid metabolism.
  
  
  METHODS
  Patients with type 2 diabetes were randomly assigned to consume either DHA-rich fish oil (containing 2400 mg/d fish oil; DHA: 1450 mg and eicosapentaenoic acid: 400 mg) or placebo for 8 weeks. Lipid profile and glycemic control parameters as well as the gene expression of PPARγ, liver x receptor-a, ATP-binding cassette A1, and CD36 in peripheral blood mononuclear cells were measured at baseline and after 8 weeks.
  
  
  RESULTS
  DHA-rich fish oil supplementation resulted in decreased triglycerides (TG) level compared with placebo group, independently of the baseline value of TG (all patients (P = .003), hypertriglyceridemic subjects (P = .01), and normotriglyceridemic subjects (P = .02)). Moreover, a higher reduction in TG level was observed in hypertriglyceridemic subjects, comparing to normotriglyceridemic subjects with DHA-rich fish oil supplementation (P = .01). Other lipid parameters as well as the expression of PPARγ, liver x receptor-a, ATP-binding cassette A1, and CD36 were not affected by DHA-rich fish oil supplementation. Only in hypertriglyceridemic subjects, DHA-rich fish oil supplementation upregulated CD36 expression, compared with the placebo group (P = .01).
  
  
  CONCLUSIONS
  DHA-rich fish oil supplementation for 8 weeks increased CD36 expression in hypertriglyceridemic subjects, which might result to higher reduction in TG level, comparing with normotriglyceridemic subjects. However, this finding should be investigated in further studies.
authors.affiliation: Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Anahita
authors.initials: A
authors.lastname: Mansoori
authors.affiliation: Community Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Gity
authors.initials: G
authors.lastname: Sotoudeh
authors.affiliation: Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Djalali
authors.affiliation: Epidemiology and Biostatistics Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Eshraghian
authors.affiliation: Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Keramatipour
authors.affiliation: Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ensieh
authors.initials: E
authors.lastname: Nasli-Esfahani
authors.affiliation: Nutrition Department, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Farzad
authors.initials: F
authors.lastname: Shidfar
authors.affiliation: Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Alvandi
authors.affiliation: Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Toupchian
authors.affiliation: Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: fkoohdan@sina.tums.ac.ir.
authors.forename: Fariba
authors.initials: F
authors.lastname: Koohdani
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D019587:Dietary Supplements / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000032:analysis*; D004311:Double-Blind Method; D005260:Female; D005395:Fish Oils / Q000737:chemistry* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000378:metabolism*; D010919:Placebos
chemical_list: D005395:Fish Oils; D047495:PPAR gamma; D010919:Placebos; D004281:Docosahexaenoic Acids
keywords: Gene expression; Lipid metabolism; Peroxisome proliferator–activated receptor γ; n-3