Kyriazis 2023 Res Sq
Kyriazis G, Serrano J, Boyd J, Mason C, Smith K, Karolyi K, Kondo S, Brown I, Maurya S, Meshram N, Serna V, Gilger J, Branch D, Gardell S, Baskin K, Ayala J, Pratley R, Goodpaster B, Coen P (2023) The TAS1R2 sweet taste receptor regulates skeletal muscle mass and fitness. https://doi.org/10.21203/rs.3.rs-2475555/v1 |
Β» Res Sq [Epub ahead of print]. PMID: 36798161 Open Access
Kyriazis George, Serrano Joan, Boyd Jordan, Mason Carter, Smith Kathleen, Karolyi Katalin, Kondo Saki, Brown Ian, Maurya Santosh, Meshram Nishita, Serna Vanida, Gilger Joshua, Branch Daniel, Gardell Stephen, Baskin Kedryn, Ayala Julio, Pratley Richard, Goodpaster Bret, Coen Paul (2023) Res Sq
Abstract: Muscle fitness and mass deteriorate under the conditions of obesity and aging for reasons yet to be fully elucidated. Herein, we describe a novel pathway linking peripheral nutrient sensing and skeletal muscle function through the sweet taste receptor TAS1R2 and the involvement of ERK2-PARP1-NAD signaling axis. Muscle-specific deletion of TAS1R2 (mKO) in mice produced elevated NAD levels due to suppressed PARP1 activity, improved mitochondrial function, increased muscle mass and strength, and prolonged running endurance. Deletion of TAS1R2 in obese or aged mice also ameliorated the decline in muscle mass and fitness arising from these conditions. Remarkably, partial loss-of-function of TAS1R2 (rs35874116) in older, obese humans recapitulated the healthier muscle phenotype displayed by mKO mice in response to exercise training. Our findings show that inhibition of the TAS1R2 signaling in skeletal muscle is a promising therapeutic approach to preserve muscle mass and function.
β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US FL Orlando Goodpaster BH
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style
Pathology: Aging;senescence, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS
Pathway: N
HRR: Oxygraph-2k
2023-02