β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway.

ABSTRACT:

Background & aims

Sterile inflammation resulting in alcoholic hepatitis (AH) occurs unpredictably after many years of excess alcohol intake. The factors responsible for the development of AH are not known but mitochondrial damage with loss of mitochondrial function are common features. Hcar2 is a G-protein coupled receptor which is activated by β-hydroxybutyrate (BHB). We aimed to determine the relevance of the BHB-Hcar2 pathway in alcoholic liver disease.

Methods

We tested if loss of BHB production can result in increased liver inflammation. We further tested if BHB supplementation is protective in AH through interaction with Hcar2, and analyzed the immune and cellular basis for protection.

Results

Humans with AH have reduced hepatic BHB, and inhibition of BHB produc

SUBMITTER: Chen Y 

PROVIDER: S-EPMC6098974 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature