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硬脂酰辅酶A去饱和酶1在代谢性疾病中的功能及相关机制研究进展

孙钦, 邢晓蕊, 刘诚, 贾单单, 王茹^*

上海体育大学运动健康学院，上海 200438

摘要

代谢性疾病主要表现为能量稳态失调，是全球面临的重大健康挑战。代谢性疾病人群常伴有与脂质代谢紊乱相关的并发症，如肥胖和非酒精性脂肪性肝病。关注脂质代谢核心基因有助于代谢性疾病及其并发症的防治工作。硬脂酰辅酶A去饱和酶1 (stearoyl-CoA desaturase 1, SCD1)是一种脂代谢关键酶，可将饱和脂肪酸转化为单不饱和脂肪酸，在能量稳态、糖脂代谢、自噬和炎症反应等众多生理和病理过程中发挥关键调控作用。Scd1的异常转录和表观遗传激活可通过调控多条信号轴导致脂质异常积累，从而促进肥胖、非酒精性脂肪性肝病、糖尿病和癌症发展。本文全面综述了SCD1作为代谢枢纽基因在常见生理和病理事件中的关键作用，并进一步从转化视角出发讨论了多学科交叉背景下SCD1新型抑制剂的潜在开发路径，以期为靶向SCD1防治代谢性疾病提供新视野和新思路。

关键词： 代谢性疾病; 硬脂酰辅酶A去饱和酶1; 糖脂代谢; 代谢枢纽

Advances in the function and mechanisms of stearoyl-CoA desaturase 1 in metabolic diseases

SUN Qin, XING Xiao-Rui, LIU Cheng, JIA Dan-Dan, WANG Ru^*

School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China

Abstract

Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and nonalcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.

Key words: metabolic diseases; stearoyl-CoA desaturase 1; glycolipid metabolism; metabolic hub

收稿日期：　　录用日期：

通讯作者：王茹　　E-mail:

DOI: 10.13294/j.aps.2025.0001

引用本文：

孙钦, 邢晓蕊, 刘诚, 贾单单, 王茹. 硬脂酰辅酶A去饱和酶1在代谢性疾病中的功能及相关机制研究进展[J]. 生理学报 2025; 77 (3): 545-562.

SUN Qin, XING Xiao-Rui, LIU Cheng, JIA Dan-Dan, WANG Ru. Advances in the function and mechanisms of stearoyl-CoA desaturase 1 in metabolic diseases. Acta Physiol Sin 2025; 77 (3): 545-562 (in Chinese with English abstract).