Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.
Front Immunol. 2023 Oct 4;14:1257596. doi: 10.3389/fimmu.2023.1257596. eCollection 2023.
Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, and remains incompletely understood. The pivotal role of liver-resident and recruited macrophages in the pathogenesis of NAFLD and NASH is widely acknowledged as a crucial factor in innate immunity. The remarkable plasticity of macrophages enables them to assume diverse activation and polarization states, dictated by their immunometabolism microenvironment and functional requirements. Recent studies in the field of immunometabolism have elucidated that alterations in the metabolic profile of macrophages can profoundly influence their activation state and functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating the polarization and activation states of macrophages, highlighting the correlation between their metabolic characteristics and the transition from pro-inflammatory to anti-inflammatory phenotypes. Additionally, we explore the potential of targeting macrophage metabolism as a promising therapeutic approach for the management of NAFLD/NASH.
非酒精性脂肪性肝病(NAFLD)及其炎症和常进展性亚型非酒精性脂肪性肝炎(NASH)已成为全球肝脏发病率的重要原因。NAFLD/NASH 的病理生理学是多方面的、可变的,并且仍不完全了解。驻留和募集的巨噬细胞在 NAFLD 和 NASH 发病机制中的关键作用被广泛认为是固有免疫的重要因素。巨噬细胞的显著可塑性使它们能够根据其免疫代谢微环境和功能要求,呈现出不同的激活和极化状态。免疫代谢领域的最新研究表明,巨噬细胞代谢谱的改变可以深刻影响其激活状态和功能,从而影响各种病理过程。本综述主要集中于阐明巨噬细胞的极化和激活状态,强调其代谢特征与从促炎表型向抗炎表型转变之间的相关性。此外,我们还探讨了靶向巨噬细胞代谢作为治疗 NAFLD/NASH 的一种有前途的治疗方法的潜力。