Role of mitochondrial depolarization and disrupted mitochondrial homeostasis in non-alcoholic steatohepatitis and fibrosis in mice.
Role of mitochondrial depolarization and disrupted mitochondrial homeostasis in non-alcoholic steatohepatitis and fibrosis in mice.
Int J Physiol Pathophysiol Pharmacol. 2019;11(5):190-204
Authors: Krishnasamy Y, Gooz M, Li L, Lemasters JJ, Zhong Z
Abstract
The pathogenesis of non-alcoholic steatohepatitis (NASH) is poorly understood. Here, relationships between mitochondrial depolarization (mtDepo) and mitochondrial homeostasis were studied in a mouse model of NASH. C57BL/6 mice were fed a Western diet (high fat, fructose and cholesterol) for 2 weeks, 2 months and 6 months, and livers were harvested for histology and biochemical analysis. Hepatic mtDepo was evaluated by intravital multiphoton microscopy. After Western diet feeding, mixed hepatic micro- and macrovesicular steatosis and leukocyte infiltration occurred at 2 weeks and continued to increase afterwards. ALT release, mild necrosis, apoptosis, and ballooning degeneration were present at 2 and 6 months. Smooth muscle α-actin expression increased at 2 weeks and longer, and increased collagen-I expression and mild fibrosis occurred at 6 months. After feeding Western diet for 2 weeks and longer, mtDepo appeared in 50-70% hepatocytes, indicating mitochondrial dysfunction at an early stage of NASH. mtDepo can initiate mitophagy, and mitophagic markers increased at 2 and 6 months. Concurrently autophagic processing became impaired. Oxidative phosphorylation proteins, mitochondria...
Source: International Journal of Physiology, Pathophysiology and Pharmacology - Category: Physiology Tags: Int J Physiol Pathophysiol Pharmacol Source Type: research
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