The muscle specific MEF2Dα2 isoform promotes muscle ketolysis and running capacity in mice.

ABSTRACT: During prolonged starvation and exhaustive exercise, when there is low availability of carbohydrates, the liver breaks down fatty acids to generate ketone bodies, which are utilized by peripheral tissues as an alternative fuel source. The transcription factor MEF2D undergoes regulated alternative splicing in the postnatal period to produce a highly conserved, muscle specific MEF2Dα2 protein isoform. Here, we discover that compared to WT mice, MEF2Dα2 exon knockout (Eko) mice display reduced running capacity and muscle expression of all three ketolytic enzymes: BDH1, OXCT1, and ACAT1. MEF2Dα2 Eko mice consistently show increased blood ketone body levels in a tolerance test, after exercise, and when fed a ketogenic diet. Lastly, using mitochondria isolated from skeletal muscle, Eko mice show

SUBMITTER: Kumar S 

PROVIDER: S-EPMC12592725 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature