title: Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c.
abstract: Nonalcoholic fatty liver disease is characterized by an abnormal accumulation of triacylglycerides in the liver in absence of significant alcohol consumption. Under these conditions, it has been observed an impaired bioavailability of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFAs). The aim of this study was to test the reversion of the prosteatotic and proinflammatory effects of high-fat diet (HFD) in the mouse liver by changing to normocaloric diet and n-3 LCPUFA supplementation. Male C57BL/6J mice were given either control diet (CD) or HFD for 12 weeks. Control and HFD groups were divided into subgroups that continue with CD or subjected to CD plus n-3 LCPUFA for 8 additional weeks. After this time, blood and liver samples were taken and metabolic, morphologic, oxidative stress, inflammatory and signaling parameters were analyzed. The dietary change from HFD to a normocaloric diet with n-3 LCPUFA supplementation significantly reduced insulin resistance and liver steatosis when compared to switching HFD to normocaloric diet alone. In addition, HFD-induced increases in adiposity, adipocyte enlargement and liver oxidative stress and inflammatory cytokine expression were suppressed by n-3 LCPUFA to control values. Importantly, n-3 LCPUFA supplementation abolish HFD-induced enhancement in hepatic SREBP-1c/PPAR-α ratios, suggesting a change in the metabolic status of the liver from a lipogenic condition to one favoring fatty acid oxidation and steatosis attenuation. These findings may provide the rational basis for the use of normocaloric diets supplemented with n-3 LCPUFA in patients with liver steatosis.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Camila G
authors.initials: CG
authors.lastname: Dossi
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Gladys S
authors.initials: GS
authors.lastname: Tapia
authors.affiliation: Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Espinosa
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: adespessailles@ug.uchile.cl.
authors.forename: Amanda
authors.initials: A
authors.lastname: D'Espessailles
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D059305:Diet, High-Fat; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D015525:Fatty Acids, Omega-3; D047493:PPAR alpha; D051780:Sterol Regulatory Element Binding Protein 1
keywords: High fat diet; Liver steatosis; PPAR-α; SREBP-1c; n-3 Long-chain polyunsaturated fatty acid