Diet Modifies Pioglitazone's Influence on Hepatic PPAR γ-Regulated Mitochondrial Gene Expression.

Diet Modifies Pioglitazone's Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression. PPAR Res. 2020;2020:3817573 Authors: Kulkarni S, Huang J, Tycksen E, Cliften PF, Rudnick DA Abstract Pioglitazone (Pio) is a thiazolidinedione (TZD) insulin-sensitizing drug whose effects result predominantly from its modulation of the transcriptional activity of peroxisome proliferator-activated-receptor-gamma (PPARγ). Pio is used to treat human insulin-resistant diabetes and also frequently considered for treatment of nonalcoholic steatohepatitis (NASH). In both settings, Pio's beneficial effects are believed to result primarily from its actions on adipose PPARγ activity, which improves insulin sensitivity and reduces the delivery of fatty acids to the liver. Nevertheless, a recent clinical trial showed variable efficacy of Pio in human NASH. Hepatocytes also express PPARγ, and such expression increases with insulin resistance and in nonalcoholic fatty liver disease (NAFLD). Furthermore, mice that overexpress hepatocellular PPARγ and Pio-treated mice with extrahepatic PPARγ gene disruption develop features of NAFLD. Thus, Pio's direct impact on hepatocellular gene expression might also be a determinant of this drug's ultimate influence on insulin resistance and NAFLD. Previous studies have characterized Pio's PPARγ-dependent effects on hepatic expression of specific adipogenic, lipogenic, and other metabolic genes. However, such ...
Source: PPAR Research - Category: Genetics & Stem Cells Tags: PPAR Res Source Type: research