PPAR Agonist Effects on Notch Signaling Mediators in Experimental Chronic Alcohol-Induced Steatohepatitis

摘要: Background: Aspartyl-Asparaginyl-Β-Hydroxylase (ASPH) is a downstream target of insulin and IGF signaling promotes cell motility for liver remodeling repair. ASPH functions in part by activating Notch HIF-1α. PPAR agonists can ameliorate steatohepatitis, hepatic resistance, reduced expression experimental alcoholic disease. Herein, we examine the effects PPAR-α, PPAR-δ, PPAR-γ on HIF-1α signaling. Methods: Long Evans rats were chronically fed control or ethanol-containing diets treated with vehicle, agonist. ASPH, Notch, HIF-1α-related genes proteins measured liver. Results: and/or inhibited chronic ethanol feeding. PPAR-δ normalized HIF-1α, PCNA protein ethanol-exposed livers. In contrast, through HES-1 was not restored. Conclusion: Therapeutic disease are mediated post-translational mechanisms that bolster ASPH-HIF-1α Alternative strategies needed to circumvent ethanol-mediated uncoupling cross-talk among insulin/IGF-1/ASPH-Notch networks.