Year: 2023
Type: preprint
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.
Source: Research Square
Authors: George Kyriazis, Joan Serrano, Jordan Boyd, Carter Mason, Kathleen Smith, Katalin Karolyi, Saki Kondo, Ian Brown, Santosh Maurya, Nishita Meshram, Vanida Serna, Joshua Gilger, Daniel Branch, Stephen Gardell, Kedryn Baskin, Julio Ayala, Richard Pratley, Bret Goodpaster, Paul Coen
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G3645598365, Southeast Resource Center for Integrated Metabolomics (SECIM), G6986349248, Ohio State University Neuroscience Center Core, Skeletal Muscle lipid and Insulin Resistance in Aging, Zeiss LSM 800 confocal microscope with Airyscan, Receptor-mediated glucose sensing and skeletal muscle function
OpenAlex ID: W4319454404