Park Hyun-Ju, Choi Juyong, Kim Hyunmi, Yang Da-Yeon, An Tae Hyeon, Lee Eun-Woo, Han Baek-Soo, Lee Sang Chul, Kim Won Kon, Bae Kwang-Hee, Oh Kyoung-Jin
Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, Republic of Korea.
Front Mol Biosci. 2023 Aug 11;10:1221669. doi: 10.3389/fmolb.2023.1221669. eCollection 2023.
Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that can progress to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis, and hepatocellular carcinoma (HCC). NAFLD ranges from simple steatosis (or nonalcoholic fatty liver [NAFL]) to NASH as a progressive form of NAFL, which is characterized by steatosis, lobular inflammation, and hepatocellular ballooning with or without fibrosis. Because of the complex pathophysiological mechanism and the heterogeneity of NAFLD, including its wide spectrum of clinical and histological characteristics, no specific therapeutic drugs have been approved for NAFLD. The heterogeneity of NAFLD is closely associated with cellular plasticity, which describes the ability of cells to acquire new identities or change their phenotypes in response to environmental stimuli. The liver consists of parenchymal cells including hepatocytes and cholangiocytes and nonparenchymal cells including Kupffer cells, hepatic stellate cells, and endothelial cells, all of which have specialized functions. This heterogeneous cell population has cellular plasticity to adapt to environmental changes. During NAFLD progression, these cells can exert diverse and complex responses at multiple levels following exposure to a variety of stimuli, including fatty acids, inflammation, and oxidative stress. Therefore, this review provides insights into NAFLD heterogeneity by addressing the cellular plasticity and metabolic adaptation of hepatocytes, cholangiocytes, hepatic stellate cells, and Kupffer cells during NAFLD progression.
非酒精性脂肪性肝病（NAFLD）是一种进行性肝病，可进展为非酒精性脂肪性肝炎（NASH）、NASH相关肝硬化和肝细胞癌（HCC）。NAFLD范围从单纯性脂肪变性（或非酒精性脂肪肝[NAFL]）到作为NAFL进展形式的NASH，其特征为脂肪变性、小叶炎症以及肝细胞气球样变，伴有或不伴有纤维化。由于NAFLD复杂的病理生理机制及其异质性，包括其广泛的临床和组织学特征，目前尚无针对NAFLD的特异性治疗药物获批。NAFLD的异质性与细胞可塑性密切相关，细胞可塑性描述了细胞响应环境刺激获得新特性或改变其表型的能力。肝脏由包括肝细胞和胆管细胞的实质细胞以及包括库普弗细胞、肝星状细胞和内皮细胞的非实质细胞组成，所有这些细胞都具有特定功能。这种异质性细胞群体具有细胞可塑性以适应环境变化。在NAFLD进展过程中，这些细胞在暴露于包括脂肪酸、炎症和氧化应激在内的多种刺激后，可在多个水平上产生多样而复杂的反应。因此，本综述通过探讨NAFLD进展过程中肝细胞、胆管细胞、肝星状细胞和库普弗细胞的细胞可塑性和代谢适应性，深入了解NAFLD的异质性。
