非酒精性脂肪性肝病(non-alcoholic fatty liver disease)与肌少症(sarcopenia)是与年龄有关的常见慢性病共病,二者存在众多共同的病理生理因素,其潜在相关机制尚未完全阐明。近年来铜死亡作为一种新型细胞死亡方式被发现,铜稳态(copper homeostasis)在多种慢性疾病中的潜在功能角色成为当前的研究热点。肝脏内铜元素的缺失与早期非酒精性脂肪性肝病的发生密切相关,而骨骼肌内铜过载可能通过多种信号途径促进肌少症的发生,以铜蓝蛋白为代表的血清铜形成的细胞外铜过载在此过程中扮演着潜在性的功能角色。本篇综述从铜代谢角度出发阐述了铜稳态失衡与早期非酒精性脂肪性肝病合并肌少症发病的可能机制,以期为临床早期改善甚至逆转这两种代谢性疾病提供分子靶点和理论基础。

Non-alcoholic fatty liver disease (NAFLD) and sarcopenia are common age-related chronic comorbidities that share many common pathophysiological factors. However, their underlying mechanisms have not been fully elucidated. In recent years, cuproptosis has been discovered as a new cell death mode, and the potential functional role of copper homeostasis in a variety of chronic diseases has become a research focus. Loss of copper in the liver is closely related to the occurrence of early NAFLD, and copper overload in skeletal muscles may promote the occurrence of sarcopenia through various signaling pathways. As indicated by ceruloplasmin levels in serum, extracellular copper overload may play a potential functional role in this process. This review discusses the possible mechanism of copper homeostasis imbalance and the onset of early NAFLD combined with sarcopenia from the perspective of copper metabolism, in order to provide molecular targets and theoretical basis for early clinical improvement or even reversal of these two metabolic diseases.