Enoyl coenzyme A hydratase 1 alleviates nonalcoholic steatohepatitis in mice by suppressing hepatic ferroptosis

Am J Physiol Endocrinol Metab. 2021 Apr 5. doi: 10.1152/ajpendo.00614.2020. Online ahead of print.ABSTRACTNon-alcoholic steatohepatitis (NASH) is a common metabolic disorder that is a major contributor to health care expenditures worldwide. Enoyl coenzyme A hydratase 1 (ECH1) is initially recognized as a key component in mitochondrial fatty acid β-oxidation, and subsequent studies have demonstrated that it regulates multiple pathophysiological processes. However, the relationship between ECH1 and NASH has remained largely unknown. Herein, we investigated the role of ECH1 in NASH progression. Adeno-associated virus-mediated genetic engineering was used to investigate the role of ECH1. Alterations in hepatic steatosis, inflammation, fibrogenesis, oxidative stress, apoptosis and liver injury were monitored using liver or serum samples from mice. ECH1 expression was significantly higher in human NASH biopsy specimens and in methionine choline-deficient (MCD) diet-fed mice. ECH1 overexpression significantly alleviated hepatic steatosis, inflammation, fibrogenesis, apoptosis and oxidative stress in livers of mice. In addition, ECH1 overexpression also reduced alanine aminotransferase and pro-inflammatory cytokine levels in serum and triglyceride levels in livers. Consistently, ECH1 knockdown suppressed this beneficial phenotype. Mechanistically, ECH1-knockdown mice treated with ferrostatin-1 (Fer-1) showed an alleviated NASH phenotype compared to the untreated knockdown mice. Mean...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Source Type: research