Wang Chih-Chen, Lin Ching-Han, Chou Hsuan-Wen, Wang Chung-Teng, Liang Yu-Cheng, Wu Hung-Tsung, Ou Horng-Yih
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
Biomedicines. 2023 Jul 7;11(7):1936. doi: 10.3390/biomedicines11071936.
Hepatic dysfunction is commonly observed in subjects with hyperthyroidism. Hepassocin is a hepatokine playing an important role in metabolic diseases and exhibiting a hepatic protective effect. Nevertheless, the relationship between hepassocin and hyperthyroidism was still unknown. In the present study, a total of 36 subjects with Graves' disease were enrolled, and we found that the alanine aminotransferase (ALT) levels were significantly decreased in parallel with the decrement in serum hepassocin concentrations at 6 months after standard treatment for hyperthyroidism. In addition, HepG2 cell line was used to investigate the role of hepassocin in hyperthyroidism-induced hepatic dysfunction. Treatment of hepassocin recombinant protein in HepG2 cells dose-dependently decreased triiodothyronine (T3)-induced ALT and aspartate aminotransferase (AST) elevation. Moreover, hepassocin significantly increased the expression of phosphoenolpyruvate carboxykinase (PEPCK) in a dose-dependent manner. Deletion of hepassocin in HepG2 cells reversed the effects of T3 on PEPCK expressions. Furthermore, we found that T3 increased the expression of hepassocin through a hepatocyte nuclear factor 1α-dependent pathway. Taken together, these results indicated a compensatory increase in serum hepassocin might have a protective role in hyperthyroidism-induced hepatic dysfunction.
肝功能障碍在甲状腺功能亢进症患者中较为常见。肝辛素是一种在代谢性疾病中起重要作用并具有肝脏保护作用的肝因子。然而，肝辛素与甲状腺功能亢进症之间的关系仍不清楚。在本研究中，共纳入了36例格雷夫斯病患者，我们发现，在甲状腺功能亢进症标准治疗6个月后，丙氨酸氨基转移酶（ALT）水平随着血清肝辛素浓度的降低而显著下降。此外，利用HepG2细胞系研究肝辛素在甲状腺功能亢进症所致肝功能障碍中的作用。在HepG2细胞中用肝辛素重组蛋白处理可剂量依赖性地降低三碘甲状腺原氨酸（T3）诱导的ALT和天冬氨酸氨基转移酶（AST）升高。此外，肝辛素以剂量依赖性方式显著增加磷酸烯醇式丙酮酸羧激酶（PEPCK）的表达。在HepG2细胞中敲除肝辛素可逆转T3对PEPCK表达的影响。此外，我们发现T3通过肝细胞核因子1α依赖性途径增加肝辛素的表达。综上所述，这些结果表明血清肝辛素的代偿性增加可能对甲状腺功能亢进症所致肝功能障碍具有保护作用。
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