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Estrogen signals through peroxisome proliferator-activated Receptor− γ coactivator 1α to reduce oxidative damage associated with diet-induced fatty liver disease

Abstract:

Background & Aims Inefficient fatty acid oxidation in mitochondria and increased oxidative damage are features of non-alcoholic fatty liver disease (NAFLD). In rodent models and patients with NAFLD, hepatic expression of peroxisome proliferator-activated receptor−γ (PPARG) coactivator 1α (PPARGC1A or PGC1A) is inversely correlated with liver fat and disease severity. A common polymorphism in this gene (rs8192678, encoding Gly482Ser) has been associated with NAFLD. We investigated whether reduced expression of PGC1A contributes to development of NAFLD using mouse models, primary hepatocytes, and human cell lines. Methods HepG2 cells were transfected with variants of PPARGC1A and protein and messenger RNA levels were measured. Mice with liver-specific hemizygous or homozygous disruption of Ppargc1a (Ppargc1af/+Alb-cre+/0 and Ppargc1af/f Alb-cre+/0 mice, respectively) were fed …