非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗和遗传易感性密切相关的代谢应激性肝损伤。NAFLD的肝损伤连续谱可从非酒精性脂肪性肝(NAFL)到非酒精性脂肪性肝炎(NASH)，甚至导致肝硬化和肝癌。NAFLD的发病机制复杂。促炎细胞因子、脂质毒性和肠道细菌代谢物在激活肝驻留巨噬细胞肝细胞(库普弗细胞，KCs)并招募循环单核细胞源巨噬细胞(MoDMacs)沉积脂肪在肝脏中起关键作用。单细胞RNA测序的应用揭示了肝巨噬细胞的显著异质性，表明肝内定位的KCs和MoDMacs在调控肝炎和NASH进展中发挥着不同的功能。本研究重点研究巨噬细胞异质性在NAFLD和NASH的发展和发生中的作用，因为先天免疫在NAFLD的发展中起关键作用。

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.