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A ketogenic diet enhances aerobic exercise adaptation and promotes muscle mitochondrial remodeling in hyperglycemic male mice

Title: A ketogenic diet enhances aerobic exercise adaptation and promotes muscle mitochondrial remodeling in hyperglycemic male mice
Authors: Pattamaprapanont, Pattarawan; Nava, Roberto C.; Grover, Rea; Formato, Mia; Cooney, Eileen M.; Pinto, Ana Paula; Alves-Wagner, Ana B.; Das, Anamica; Guan, Yuntian; Annambhotla, Meghana; Acharya, Saanvi; Rivas, Donato A.; Lessard, Sarah J.
Publication Year: 2025
Collection: VTechWorks (VirginiaTech)
Description: VO 2 peak is a key health benefit of aerobic exercise; however, chronic hyperglycemia is associated with persistently low VO 2 peak due to an impaired adaptive response to training. Here, we show that reducing blood glucose with a carbohydrate-restricted, high fat ketogenic diet can restore aerobic exercise adaptation in male mice with hyperglycemia. Hyperglycemic mice received standard high-carbohydrate chow (CHOW), which sustains high blood glucose; or a ketogenic diet (KETO), which normalizes blood glucose levels. After aerobic exercise training, improvements in VO 2 peak are blunted in CHOW, but restored by KETO. Increased VO 2 peak in KETO is associated with enhanced aerobic remodeling of skeletal muscle, including a more oxidative fiber-type and increased capillary density. Moreover, KETO induces exercise-independent effects on muscle mitochondrial remodeling and substrate selection, significantly increasing fatty acid oxidation and down-regulating glucose metabolism. We identify a ketogenic diet as a potential therapy to improve aerobic exercise adaptation in the growing population with hyperglycemia. ; Published version
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://hdl.handle.net/10919/141584
DOI: 10.21203/rs.3.rs-5814971/v1
Availability: https://hdl.handle.net/10919/141584; https://doi.org/10.21203/rs.3.rs-5814971/v1
Rights: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.EC3D7607
Database: BASE