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Dynamics of Liver Macrophage Subsets in a Novel Mouse Model of Non-Alcoholic Steatohepatitis Using C57BL/6 Mice

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(+...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604124/
https://www.ncbi.nlm.nih.gov/pubmed/37893033
http://dx.doi.org/10.3390/biomedicines11102659
Descripción
Sumario: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.