The muscle specific MEF2D⍺2 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 MEF2D⍺2 protein isoform. Here, we discover that compared to WT mice, MEF2D⍺2 exon knockout (Eko) mice display reduced running capacity and muscle expression of all three ketolytic enzymes: BDH1, OXCT1, and ACAT1. MEF2D⍺2 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: Sushil Kumar 

PROVIDER: S-SCDT-10_1038-S44319-025-00578-3 | biostudies-other |

REPOSITORIES: biostudies-other