Proteomics

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Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding


ABSTRACT: Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study sought to determine if ketone flux in skeletal and cardiac muscles plays an essential role in conferring the health benefits of an intermittent TRF (iTRF) schedule. Notably, we found that the ketolytic enzyme, beta-hydroxybutyrate dehydrogenase 1 (BDH1), is uniquely enriched in isolated mitochondria derived from heart and red/oxidative skeletal muscles, which also have high capacity for fatty acid oxidation (FAO). Using mice with muscle/heart-specific BDH1 deficiency, we discover that this enzyme is required for optimal FAO efficiency and exercise tolerance during acute fasting. Additionally, iTRF leads to robust molecular remodeling of muscle tissues and BDH1 flux is indeed required for the full adaptive benefits of this regimen, including increased lean mass, mitochondrial hormesis, and metabolic rerouting of pyruvate. In sum, ketone utilization enhances mitochondrial bioenergetics and supports iTRF-induced remodeling of skeletal muscle and heart.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Deborah M. Muoio 

PROVIDER: PXD047114 | JPOST Repository | Fri Feb 09 00:00:00 GMT 2024

REPOSITORIES: jPOST

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Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding.

Williams Ashley S AS   Crown Scott B SB   Lyons Scott P SP   Koves Timothy R TR   Wilson Rebecca J RJ   Johnson Jordan M JM   Slentz Dorothy H DH   Kelly Daniel P DP   Grimsrud Paul A PA   Zhang Guo-Fang GF   Muoio Deborah M DM  

Cell metabolism 20240201 2


Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. Notably, we found that the ketolytic enzyme beta-hydroxybutyrate dehydrogenase 1 (BDH1) is uniquely enriched in isolated mitochondria derived from heart and red/oxidative skeletal muscles, which also have high capacity for fatty acid oxidation (F  ...[more]

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