《生命科学》 2026, 38(10): 1718-1727

丝氨酸调控代谢相关脂肪性肝病的作用与机制

周博军^1,2 , 张诗岩^1,2 , 张展博² , 周诗洁³ , 孟化^2,*

¹北京体育大学运动人体科学学院， 北京 100084 ²中日友好医院普外科代谢减重中心，北京 100029 ³杭州医学院检验医学与生物工程学院，杭州 311399

摘　要：

在全球范围内，代谢相关脂肪性肝病（metabolic dysfunction-associated steatotic liver disease，MASLD）的疾病负担持续加重，而安全、有效且可长期干预的代谢靶点仍然有限。尽管丝氨酸被归为非必需氨基酸，但多项跨物种、跨人群研究一致发现，在肥胖、胰岛素抵抗等代谢异常背景下，靶器官的丝氨酸循环水平往往下降，提示丝氨酸可能在代谢紊乱或机体应激状态下发挥条件必需氨基酸的作用。作为代谢网络的核心节点之一，丝氨酸通过参与一碳代谢与氧化还原稳态维持、支持线粒体功能与能量代谢、调节脂质代谢与鞘脂合成、影响免疫细胞功能与炎症反应，以及促进肝脏修复与再生等多种生物学过程，调控MASLD的发生、进展与疾病结局。本研究系统回顾了细胞、动物与临床研究证据，梳理丝氨酸合成、缺乏或相关通路受限的关键表型及其潜在机制，以期为MASLD的风险识别、机制研究与综合管理提供参考依据。

通讯作者：孟化 , Email:menghuade@hotmail.com

Role and mechanisms of serine in regulating metabolic dysfunction-associated steatotic liver disease

ZHOU Bo-Jun^1,2 , ZHANG Shi-Yan^1,2 , ZHANG Zhan-Bo² , ZHOU Shi-Jie³ , MENG Hua^2,*

¹School of Sport Science, Beijing Sport University, Beijing 100084, China ²Department of General Surgery and Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing 100029, China ³School of Laboratory Medicine and School of Biological Engineering, Hangzhou Medical College, Hangzhou 311399, China

Abstract:

The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to increase, while safe, effective, and sustainable therapeutic targets for long-term metabolic intervention remain limited. Although serine is classified as a non-essential amino acid, accumulating evidence from cross-species and cross-population studies consistently demonstrates that serine flux in target organs is often reduced under metabolic disorders such as obesity and insulin resistance, suggesting that serine may function as a conditionally essential amino acid under metabolic stress or physiological challenges. As a key node in metabolic networks, serine regulates the development, progression, and outcomes of MASLD through multiple biological processes, including one-carbon metabolism and redox homeostasis, mitochondrial function and energy metabolism, lipid metabolism and sphingolipid synthesis, immune cell function and inflammatory responses, as well as hepatic repair and regeneration. This review systematically summarizes evidence from cellular, animal, and clinical studies, highlighting the key phenotypes and potential mechanisms associated with altered serine biosynthesis, deficiency, or disruption of serine-related metabolic pathways. These insights may provide new perspectives for risk stratification, mechanistic investigation, and comprehensive management of MASLD.

Communication Author：MENG Hua , Email:menghuade@hotmail.com