title: N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-α upregulation and NF-κB DNA binding abrogation.
abstract: METHODS
  Dietary n-3 long-chain PUFAs (n-3 LCPUFAs) supplementation was studied in an HFD-induced (HFD is high-fat diet) steatosis and inflammation in relation to peroxisome proliferator-activated receptor alpha (PPAR-α) and nuclear factor κB (NF-κB) signaling.
  
  
  RESULTS
  Male C57BL/6J mice received (i) control diet (10% fat, 20% protein, 70% carbohydrate), (ii) control diet plus n-3 LCPUFAs (daily doses of 108 mg/kg body weight of eicosapentaenoic acid plus 92 mg/kg body weight of docosahexaenoic acid), (iii) HFD (60% fat, 20% protein, 20% carbohydrate), or (iv) HFD plus n-3 LCPUFAs for 12 wk. PPAR-α, tumor necrosis factor alpha (TNF-α), and IL-1β mRNA expression, acyl-CoA oxidase 1 (ACOX1), and carnitine-acyl-CoA transferase 1 (CAT-I) protein contents, and NF-κB DNA binding activity were measured. HFD significantly decreased liver PPAR-α, ACOX1, and CAT-I levels with NF-κB activation, higher TNF-α and IL-1β expression, and steatosis development. These changes were either reduced or normalized to control values in animals subjected to HFD plus n-3 LCPUFAs, with establishment of an inverse association between NF-κB activation and PPAR-α mRNA expression (r = -0.66, p < 0.0001).
  
  
  CONCLUSIONS
  Data presented indicate that n-3 LCPUFAs supplementation prevents liver steatosis and inflammation induced by HFD, with underlying mechanisms involving enhanced PPAR-α signaling and diminished NF-κB activation.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Gladys
authors.initials: G
authors.lastname: Tapia
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Valenzuela
authors.forename: Alejandra
authors.initials: A
authors.lastname: Espinosa
authors.forename: Pamela
authors.initials: P
authors.lastname: Romanque
authors.forename: Camila
authors.initials: C
authors.lastname: Dossi
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez-Mañán
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
authors.forename: Amanda
authors.initials: A
authors.lastname: D'Espessailles
mesh_terms: D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D015525:Fatty Acids, Omega-3; D053583:Interleukin-1beta; D016328:NF-kappa B; D047493:PPAR alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042962:Acyl-CoA Oxidase
keywords: High-fat diet; Liver steatosis; Nuclear factor κB; Peroxisome proliferator-activated receptor alpha; n-3 long-chain PUFA