BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21.

ABSTRACT:

Background

Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive.

Results

We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to car

SUBMITTER: Zheng H 

PROVIDER: S-EPMC11344321 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature