Paudel Devendra, Hao Fuhua, Goand Umesh K, Tian Sangshan, Koehle Anthony M, Nguyen Loi V, Tian Yuan, Patterson Andrew D, Singh Vishal
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA.
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA.
iScience. 2024 Sep 13;27(10):110940. doi: 10.1016/j.isci.2024.110940. eCollection 2024 Oct 18.
Excessive alcohol consumption is a major global health problem. Individuals with alcoholic liver disease often exhibit elevated serum total bile acids (TBAs). Nevertheless, the extent to which high TBA contributes to alcohol-associated liver disease (AALD) remains elusive. To investigate this, wild-type mice were categorized into normal (nTBA) and high (hTBA) TBA groups. Both groups underwent chronic-binge ethanol feeding for 4 weeks, followed by additional weekly ethanol doses. Ethanol feeding worsened AALD in both male and female mice with elevated serum TBA, characterized by liver dysfunction and steatosis. Decreased hepatic expression of genes involved in mitochondrial β-oxidation and lipid transport in ethanol-fed hTBA mice suggests that altered fatty acid metabolism contributed to AALD. Our findings, which represent the first to link high serum TBA to increased AALD susceptibility, underscore the importance of proactive serum TBA screening as a valuable tool for identifying individuals at high risk of developing AALD.
过度饮酒是一个重大的全球健康问题。患有酒精性肝病的个体通常血清总胆汁酸（TBA）水平升高。然而，高TBA在多大程度上导致酒精相关性肝病（AALD）仍不清楚。为了研究这一问题，将野生型小鼠分为正常（nTBA）和高（hTBA）TBA组。两组均接受为期4周的慢性暴饮乙醇喂养，随后每周额外给予乙醇剂量。乙醇喂养使血清TBA升高的雄性和雌性小鼠的AALD恶化，其特征为肝功能障碍和脂肪变性。乙醇喂养的hTBA小鼠中线粒体β氧化和脂质转运相关基因的肝脏表达降低，这表明脂肪酸代谢改变导致了AALD。我们的研究结果首次将高血清TBA与AALD易感性增加联系起来，强调了主动进行血清TBA筛查作为识别AALD高危个体的重要工具的重要性。
