title: The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease with ever-growing incidence in the industrialized world. It starts with the simple accumulation of lipids in the hepatocyte and can progress to the more severe nonalcoholic steatohepatitis (NASH), which is associated with inflammation, fibrosis, and cirrhosis. There is increasing awareness that reactive oxygen species and electrophiles are implicated in the pathogenesis of NASH. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a positive regulator of the expression of a battery of genes involved in the protection against oxidative/electrophilic stress. In rodents, Nrf2 is also known to participate in hepatic fatty acid metabolism, as a negative regulator of genes that promote hepatosteatosis. We review relevant evidence in the literature that these two mechanisms may contribute to the protective role of Nrf2 in the development of hepatic steatosis and in the progression to steatohepatitis, particularly in young animals. We propose that age may be a key to explain contradictory findings in the literature. In summary, Nrf2 mediates the crosstalk between lipid metabolism and antioxidant defense mechanisms in experimental models of NAFLD, and the nutritional or pharmacological induction of Nrf2 represents a promising potential new strategy for its prevention and treatment.
authors.affiliation: Basic and Clinical Research on Iron Biology Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150180 Porto, Portugal ; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Sílvia S
authors.initials: SS
authors.lastname: Chambel
authors.affiliation: Basic and Clinical Research on Iron Biology Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150180 Porto, Portugal ; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Santos-Gonçalves
authors.affiliation: Basic and Clinical Research on Iron Biology Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150180 Porto, Portugal ; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Tiago L
authors.initials: TL
authors.lastname: Duarte
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species