Sun Qin, Xing Xiao-Rui, Liu Cheng, Jia Dan-Dan, Wang Ru
School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
Sheng Li Xue Bao. 2025 Jun 25;77(3):545-562. doi: 10.13294/j.aps.2025.0001.
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 non-alcoholic 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 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.
以能量稳态失衡为特征的代谢性疾病是一项重大的全球健康挑战。患有代谢性疾病的个体常常遭受与脂质代谢紊乱相关的并发症,如肥胖症和非酒精性脂肪性肝病(NAFLD)。了解参与脂质代谢的核心基因可以推进这些疾病的预防和治疗策略。硬脂酰辅酶A去饱和酶1(SCD1)是脂质代谢中的一种关键酶,可将饱和脂肪酸转化为单不饱和脂肪酸。SCD1在众多生理和病理过程中发挥着关键的调节作用,包括能量稳态、糖脂代谢、自噬和炎症。SCD1的异常转录和表观遗传激活通过调节多个信号轴导致脂质异常积累,从而促进肥胖症、NAFLD、糖尿病和癌症的发展。本综述全面总结了SCD1作为代谢枢纽基因在各种(病理)生理背景下的关键作用。此外,还探讨了潜在的转化途径,重点是跨学科领域新型SCD1抑制剂的开发,旨在为在代谢性疾病的预防和治疗中靶向SCD1提供新的见解和方法。