Hepatic activating transcription factor 3 protects against systemic inflammation by attenuating lipotoxicity.

ABSTRACT:

Background

Activating transcription factor 3 (ATF3) is known to play a key role in regulating lipid and lipoprotein metabolism. However, the effects of hepatic ATF3 on systemic inflammation and the underlying mechanisms remain unclear.

Methods

An adeno-associated virus with hepatocyte-specific promoter was used to construct mouse models with hepatocyte-specific overexpression or knockdown of ATF3.

Results

Overexpression of human ATF3 in hepatocytes prevented high-fat (HF) diet-induced systemic inflammation in C57BL/6J mice and reversed systemic inflammation in db/db mice. Conversely, hepatocyte-specific loss of ATF3 aggravated diet-induced systemic inflammation. In co-culture studies, the anti-inflammatory effect of hepatocyte ATF3 on adipose tiss

SUBMITTER: Hu C 

PROVIDER: S-EPMC12648580 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature