Makiuchi Nana, Takano Shun, Tada Yuki, Kasai Kaichi, Igarashi Naoya, Kani Koudai, Kato Miyuna, Goto Kana, Matsuura Yudai, Ichimura-Shimizu Mayuko, Furusawa Yukihiro, Tsuneyama Koichi, Nagai Yoshinori
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, 3-8-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Biomedicines. 2023 Sep 28;11(10):2659. doi: 10.3390/biomedicines11102659.
Macrophages are critical for the development of non-alcoholic steatohepatitis (NASH). Our previous findings in TSNO mouse livers showed that an iHFC (high-fat/cholesterol/cholate) diet induced liver fibrosis similar to human NASH and led to the accumulation of distinct subsets of macrophage: CD11c/Ly6C and CD11c/Ly6C cells. CD11c/Ly6C cells were associated with the promotion of advanced liver fibrosis in NASH. On the other hand, CD11c/Ly6C cells exhibited an anti-inflammatory effect and were involved in tissue remodeling processes. This study aimed to elucidate whether an iHFC diet with reduced cholic acid (iHFC#2 diet) induces NASH in C57BL/6 mice and examine the macrophage subsets accumulating in the liver. Histological and quantitative real-time PCR analyses revealed that the iHFC#2 diet promoted inflammation and fibrosis indicative of NASH in the livers of C57BL/6 mice. Cell numbers of Kupffer cells decreased and recruited macrophages were accumulated in the livers of iHFC#2 diet-fed C57BL/6 mice. Notably, the iHFC#2 diet resulted in the accumulation of three macrophage subsets in the livers of C57BL/6 mice: CD11c/Ly6C, CD11c/Ly6C, and CD11c/Ly6C cells. However, CD11c/Ly6C cells were not distinct populations in the iHFC-fed TSNO mice. Thus, differences in cholic acid content and mouse strain affect the macrophage subsets that accumulate in the liver.
巨噬细胞对非酒精性脂肪性肝炎（NASH）的发展至关重要。我们之前在TSNO小鼠肝脏中的研究结果表明，高脂/胆固醇/胆酸盐（iHFC）饮食可诱导类似于人类NASH的肝纤维化，并导致不同亚群巨噬细胞的积累：CD11c/Ly6C⁺和CD11c/Ly6C⁻细胞。CD11c/Ly6C⁺细胞与NASH中晚期肝纤维化的进展相关。另一方面，CD11c/Ly6C⁻细胞表现出抗炎作用，并参与组织重塑过程。本研究旨在阐明胆酸含量降低的iHFC饮食（iHFC#2饮食）是否会在C57BL/6小鼠中诱导NASH，并检查肝脏中积累的巨噬细胞亚群。组织学和定量实时PCR分析显示，iHFC#2饮食促进了C57BL/6小鼠肝脏中指示NASH的炎症和纤维化。在喂食iHFC#2饮食的C57BL/6小鼠肝脏中，库普弗细胞数量减少，募集的巨噬细胞积累。值得注意的是，iHFC#2饮食导致C57BL/6小鼠肝脏中三个巨噬细胞亚群的积累：CD11c/Ly6C⁺、CD11c/Ly6C⁻和CD11c/Ly6G⁺细胞。然而，在喂食iHFC的TSNO小鼠中，CD11c/Ly6G⁺细胞并非不同的群体。因此，胆酸含量和小鼠品系的差异会影响肝脏中积累的巨噬细胞亚群。
