The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity
Year: 2024
Type: article
Abstract: The bioavailability of nicotinamide adenine dinucleotide (NAD) is vital for skeletal muscle health, yet the mechanisms or signals regulating NAD homeostasis remain unclear. Here, we uncover a pathway connecting peripheral glucose sensing to the modulation of muscle NAD through TAS1R2, the sugar-sensing G protein-coupled receptor (GPCR) initially identified in taste perception. Muscle TAS1R2 receptor stimulation by glucose and other agonists induces ERK1/2-dependent phosphorylation and activation of poly(ADP-ribose) polymerase1 (PARP1), a major NAD consumer in skeletal muscle. Consequently, muscle-specific deletion of TAS1R2 (mKO) in male mice suppresses PARP1 activity, elevating NAD levels and enhancing mitochondrial capacity and running endurance. Plasma glucose levels negatively correlate with muscle NAD, and TAS1R2 receptor deficiency enhances NAD responses across the glycemic range, implicating TAS1R2 as a peripheral energy surveyor. These findings underscore the role of GPCR signaling in NAD regulation and propose TAS1R2 as a potential therapeutic target for maintaining muscle health.
Source: Nature Communications
Authors: Joan Serrano, Jordan Boyd, Ian S. Brown, Carter Mason, Kathleen R. Smith, Katalin Karolyi, Santosh K. Maurya, Nishita N. Meshram, Vanida Serna, Grace M. Link, Stephen J. Gardell, George A. Kyriazis
Institutions: The Ohio State University, AdventHealth Orlando
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Health and Human Services, U.S. Department of Agriculture, American Heart Association, National Institutes of Health, National Institute of Food and Agriculture, Agricultural Research Service, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G281250818, G3645598365, G5651803727, Southeast Resource Center for Integrated Metabolomics (SECIM), G6986349248, Ohio State University Neuroscience Center Core, G8145718841, Zeiss LSM 800 confocal microscope with Airyscan, G888185492, Receptor-mediated glucose sensing and skeletal muscle function
OpenAlex ID: W4399457934