Hepatic Damage Caused by Long-term High Cholesterol Intake Induces a Dysfunctional Restorative Macrophage Population in Experimental NASH

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Sep 26

PMID 36159810

Authors

Ana C Maretti-Mira

Matthew P Salomon

Angela M Hsu

Gary C Kanel

Lucy Golden-Mason

Affiliations

Soon will be listed here.

Abstract

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.

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