BDK inhibition acts as a catabolic switch to mimic fasting and improve metabolism in mice.

ABSTRACT:

Objective

Branched chain amino acid (BCAA) catabolic defects are implicated to be causal determinates of multiple diseases. This work aimed to better understand how enhancing BCAA catabolism affected metabolic homeostasis as well as the mechanisms underlying these improvements.

Methods

The rate limiting step of BCAA catabolism is the irreversible decarboxylation by the branched chain ketoacid dehydrogenase (BCKDH) enzyme complex, which is post-translationally controlled through phosphorylation by BCKDH kinase (BDK). This study utilized BT2, a small molecule allosteric inhibitor of BDK, in multiple mouse models of metabolic dysfunction and NAFLD including the high fat diet (HFD) model with acute and chronic treatment paradigms, the choline deficient and methionine minimal hig

SUBMITTER: Bollinger E 

PROVIDER: S-EPMC9589198 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature