Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation.

ABSTRACT: Acetylation coordinates many biological processes to ensure cells respond appropriately to nutrients. However, how acetylation regulates lipid surplus-induced inflammation remains poorly understood. Here, we found that a high-fat diet (HFD) enhanced mitochondrial fatty acid β-oxidation, which enhanced acetyl-CoA levels in the liver of the large yellow croaker. The HFD activated ACLY to govern the "citrate transport" to transfer acetyl-CoA from the mitochondria to the nucleus. Elevated acetyl-CoA activated CBP to increase p65 acetylation and then aggravated inflammation. SIRT1 was deactivated with a decline in NAD⁺/NADH, which further aggravated inflammation. Therefore, acetylation-dependent regulation of transcription factor activity is an adaptation to proinflammatory stimuli u

SUBMITTER: Chen Q 

PROVIDER: S-EPMC8551082 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature