[Macrophage heterogeneity role in NAFLD and NASH disease progression]

Zhonghua Gan Zang Bing Za Zhi. 2023 Jul 20;31(7):770-775. doi: 10.3760/cma.j.cn501113-20220428-00223.
[Article in Chinese]

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗和遗传易感密切相关的代谢应激性肝损伤。NAFLD是一个从非酒精性脂肪肝到非酒精性脂肪性肝炎的连续性的肝脏损伤,甚至导致肝硬化和肝癌。NAFLD发病机制复杂,其中促炎细胞因子、脂毒性和肠道细菌产物促进肝脏驻留的肝巨噬细胞的激活,并招募循环中单核来源的巨噬细胞向肝脏内聚集发挥关键作用。随着单细胞RNA测序的应用,揭示了肝脏巨噬细胞具有很大的异质性,表明肝脏驻留的肝巨噬细胞和单核来源的巨噬细胞在调节肝脏炎症和非酒精性脂肪性肝炎进展中发挥有不同的功能。鉴于固有免疫在NAFLD发病机制中的核心作用,现重点讨论巨噬细胞的异质性在NAFLD和非酒精性脂肪性肝炎发生和发展中的作用机制。.

Keywords: Hepatic macrophage; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis.

Publication types

  • English Abstract

MeSH terms

  • Disease Progression
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Macrophages / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology