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Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH

Maretti-Mira, Ana C. ; Salomon, Matthew P. ; Hsu, Angela M. ; Kanel, Gary C. ; Golden-Mason, Lucy

Frontiers in immunology, 2022-09, Vol.13, p.968366-968366 [Periódico revisado por pares]

Frontiers Media S.A

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  • Título:
    Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
  • Autor: Maretti-Mira, Ana C. ; Salomon, Matthew P. ; Hsu, Angela M. ; Kanel, Gary C. ; Golden-Mason, Lucy
  • Assuntos: cholesterol ; Immunology ; innate immunity ; Kupffer cells ; nonalcoholic fatty liver disease (NAFLD) ; RNAseq ; tissue macrophages
  • É parte de: Frontiers in immunology, 2022-09, Vol.13, p.968366-968366
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
    Edited by: Allan R. Brasier, University of Wisconsin-Madison, United States
    Reviewed by: Juqiang Han, People’s Liberation Army General Hospital, China; Young S. Hahn, University of Virginia, United States
  • Descrição: Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However, the impact of cholesterol on these cells in the setting of NASH remains elusive. Here, we demonstrate that the dietary cholesterol content directly affects hepatic macrophage global gene expression. Our findings suggest that the modifications triggered by prolonged high cholesterol intake induce long-lasting hepatic damage and support the expansion of a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction. The present work expands the understanding of the modulatory effects of cholesterol on innate immune cell transcriptome and may help identify novel therapeutic targets for NASH intervention.
  • Editor: Frontiers Media S.A
  • Idioma: Inglês
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