Hepatocyte-Macrophage Acetoacetate Shuttle Protects against Tissue Fibrosis.

ABSTRACT: Metabolic plasticity has been linked to polarized macrophage function, but mechanisms connecting specific fuels to tissue macrophage function remain unresolved. Here we apply a stable isotope tracing, mass spectrometry-based untargeted metabolomics approach to reveal the metabolome penetrated by hepatocyte-derived glucose and ketone bodies. In both classically and alternatively polarized macrophages, [¹³C]acetoacetate (AcAc) labeled ∼200 chemical features, but its reduced form D-[¹³C]β-hydroxybutyrate (D-βOHB) labeled almost none. [¹³C]glucose labeled ∼500 features, and while unlabeled AcAc competed with only ∼15% of them, the vast majority required the mitochondrial enzyme succinyl-coenzyme A-oxoacid transferase (SCOT). AcAc carbon labeled metabolites with

SUBMITTER: Puchalska P 

PROVIDER: S-EPMC6559243 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature