# NASH-associated macrophages: regulation and role in disease pathogenesis

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $510,001

## Abstract

Project Summary/Abstract
The obesity epidemic has increased the prevalence of non-alcoholic fatty liver disease, which ranges from
clinically benign hepatic steatosis to non-alcoholic steatohepatitis (NASH). The latter represents a more severe
disease state featured by the presence of chronic liver injury, inflammation, and liver fibrosis, which increases
the risk for end-stage liver disease such as cirrhosis and hepatocellular carcinoma (HCC). Macrophages play
an integral role in host defense, tissue homeostasis, and disease progression. Altered macrophage
polarization, characterized by changes in its transcriptional and functional states, has been causally linked to
the pathogenesis of metabolic disease including NASH. Despite this, the nature of macrophage heterogeneity,
disease-associated reprogramming, and its contribution to NASH progression remains obscure. To address
these challenges, we recently performed single-cell RNA sequencing analysis on liver cells isolated from
healthy and diet-induced NASH mice. Our study uncovered a unique population of NASH-associated
macrophages (NAMs) that exhibits strong association with mouse and human NASH. Several important
questions emerge from these findings regarding the pathophysiological signals that trigger NAM induction, its
role in NASH pathogenesis, and the underlying mechanisms. Based on a body of preliminary data, we
hypothesize that intrahepatic pathogenic stimuli drive NAM induction during NASH, thereby reshaping the liver
microenvironment and exacerbating disease progression. In this proposal, we plan to elucidate the signaling
pathways that promote NAM induction and critically assess its role in disease pathogenesis. We plan to
explore the mechanisms through which NAMs contribute to the reprogramming of the liver microenvironment.

## Key facts

- **NIH application ID:** 10802401
- **Project number:** 5R01DK136179-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jiandie D Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $510,001
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802401

## Citation

> US National Institutes of Health, RePORTER application 10802401, NASH-associated macrophages: regulation and role in disease pathogenesis (5R01DK136179-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10802401. Licensed CC0.

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