Lu Qianrang, Tian Xinyao, Wu Hao, Huang Jiacheng, Li Mengxia, Mei Zhibin, Zhou Lin, Xie Haiyang, Zheng Shusen
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China.
Front Physiol. 2021 Aug 30;12:710420. doi: 10.3389/fphys.2021.710420. eCollection 2021.
Nonalcoholic fatty liver disease (NAFLD) is often accompanied by systemic metabolic disorders such as hyperglycemia, insulin resistance, and obesity. The relationship between NAFLD and systemic metabolic disorders has been well reviewed before, however, the metabolic changes that occur in hepatocyte itself have not been discussed. In NAFLD, many metabolic pathways have undergone significant changes in hepatocyte, such as enhanced glycolysis, gluconeogenesis, lactate production, tricarboxylic acid (TCA) cycle, and decreased ketone body production, mitochondrial respiration, and adenosine triphosphate (ATP) synthesis, which play a role in compensating or exacerbating disease progression, and there is close and complex interaction existed between these metabolic pathways. Among them, some metabolic pathways can be the potential therapeutic targets for NAFLD. A detailed summary of the metabolic characteristics of hepatocytes in the context of NAFLD helps us better understand the pathogenesis and outcomes of the disease.
非酒精性脂肪性肝病(NAFLD)常伴有全身代谢紊乱,如高血糖、胰岛素抵抗和肥胖。此前已有关于NAFLD与全身代谢紊乱之间关系的详尽综述,然而,尚未探讨肝细胞自身发生的代谢变化。在NAFLD中,肝细胞内许多代谢途径发生了显著变化,如糖酵解、糖异生、乳酸生成、三羧酸(TCA)循环增强,而酮体生成、线粒体呼吸和三磷酸腺苷(ATP)合成减少,这些变化在疾病进展的代偿或加剧过程中发挥作用,并且这些代谢途径之间存在密切而复杂的相互作用。其中,一些代谢途径可能成为NAFLD的潜在治疗靶点。对NAFLD背景下肝细胞代谢特征的详细总结有助于我们更好地理解该疾病的发病机制和转归。