Xu Chuze, Ezzi Sohaib Hasan Abdullah, Zou Xiaodi, Dong Yanzhao, Alhaskawi Ahmad, Zhou Haiying, Kota Vishnu Goutham, Abdulla Mohamed Hasan Abdulla Hasan, Abdalbary Sahar Ahmed, Lu Hui
School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Orthopedics, Third Xiangya Hospital, Central South University, Changsha, China.
Cytokine. 2025 Jun;190:156933. doi: 10.1016/j.cyto.2025.156933. Epub 2025 Apr 1.
Tumor necrosis factor (TNF) is identified as a pro-inflammatory cytokine critical to the pathology of liver disease. In the carbohydrate metabolism, TNF has been demonstrated to impede the insulin signaling pathway, thereby precipitating glucose intolerance and insulin resistance. In lipid metabolism, TNF upregulates genes implicated in fatty acid synthesis, resulting in increased lipid accumulation within the liver. In amino acid metabolism, TNF has shown to promote the gene expression for amino acid catabolism, leading to decreased protein synthesis. Additionally, TNF stimulates the production of other chemokines and inflammatory cytokines that can further exacerbate liver injury. Overall, TNF is crucial in developing liver diseases by disrupting various metabolic pathways in the liver, causing insulin resistance, lipid accumulation, and decreased protein synthesis. This review summarizes the present understanding of TNF's role in the regulation of carbohydrate, lipid and amino acid metabolism in liver disease together with its potential therapeutic implications.
肿瘤坏死因子(TNF)被认为是一种对肝脏疾病病理过程至关重要的促炎细胞因子。在碳水化合物代谢中,TNF已被证明会阻碍胰岛素信号通路,从而引发葡萄糖不耐受和胰岛素抵抗。在脂质代谢中,TNF上调与脂肪酸合成相关的基因,导致肝脏内脂质积累增加。在氨基酸代谢中,TNF已显示会促进氨基酸分解代谢的基因表达,导致蛋白质合成减少。此外,TNF刺激其他趋化因子和炎性细胞因子的产生,这会进一步加重肝损伤。总体而言,TNF通过扰乱肝脏中的各种代谢途径、导致胰岛素抵抗、脂质积累和蛋白质合成减少,在肝脏疾病的发展中起关键作用。本综述总结了目前对TNF在肝脏疾病中调节碳水化合物、脂质和氨基酸代谢的作用及其潜在治疗意义的理解。