Wang Z, Wang H, Sun H
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Physiol Res. 2025 Apr 30;74(2):175-187. doi: 10.33549/physiolres.935453.
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of cirrhosis and liver cancer. Its global prevalence increases annually, significantly affecting quality of life. Only a few patients manage to alleviate NAFLD through lifestyle modifications. The pathogenic mechanisms and therapeutic targets of this disease remain inadequately explored. In recent years, many studies highlighted a close relationship between the thyroid-stimulating hormone (TSH) and NAFLD. TSH has been shown to promote fat accumulation in the liver by participating in the ab initio synthesis, uptake and secretion of lipids. Moreover, TSH exacerbates hepatocyte inflammation and fibrosis by inducing endoplasmic reticulum stress and promoting the release of inflammatory factors. Although some of the conclusions remain controversial and are subject to debate, exploring the connection and possible pathways between TSH and NAFLD is crucial. Such research could advance early clinical prevention and intervention strategies, thereby reducing the incidence of severe NAFLD-associated comorbidities. Therefore, this review aims to summarize currently available evidence on the association between TSH and NAFLD focusing on the following objectives: elucidating the relationship between TSH and NAFLD; TSH may be a potential target for NAFLD prevention; exploring potential molecular targets that could block TSH-mediated promotion of NAFLD.
非酒精性脂肪性肝病(NAFLD)是肝硬化和肝癌的主要病因之一。其全球患病率逐年上升,严重影响生活质量。只有少数患者通过生活方式改变成功缓解了NAFLD。该疾病的致病机制和治疗靶点仍未得到充分探索。近年来,许多研究强调了促甲状腺激素(TSH)与NAFLD之间的密切关系。TSH已被证明通过参与脂质的从头合成、摄取和分泌来促进肝脏脂肪堆积。此外,TSH通过诱导内质网应激和促进炎症因子释放,加剧肝细胞炎症和纤维化。尽管一些结论仍存在争议且有待讨论,但探索TSH与NAFLD之间的联系及可能途径至关重要。此类研究可推进早期临床预防和干预策略,从而降低严重NAFLD相关合并症的发生率。因此,本综述旨在总结目前关于TSH与NAFLD关联的现有证据,重点关注以下目标:阐明TSH与NAFLD之间的关系;TSH可能是NAFLD预防的潜在靶点;探索可能阻断TSH介导的NAFLD促进作用的潜在分子靶点。