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- Title
The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity.
- Authors
Serrano, Joan; Boyd, Jordan; Brown, Ian S.; Mason, Carter; Smith, Kathleen R.; Karolyi, Katalin; Maurya, Santosh K.; Meshram, Nishita N.; Serna, Vanida; Link, Grace M.; Gardell, Stephen J.; Kyriazis, George A.
- 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. The bioavailability of NAD is vital for muscle health. Here, the authors unveil a pathway from glucose sensing to muscle NAD modulation via the TAS1R2 receptor, suggesting TAS1R2 as a therapeutic target for muscle health preservation.
- Subjects
NAD (Coenzyme); SKELETAL muscle; HOMEOSTASIS; G protein coupled receptors; BLOOD sugar; GLUCOSE; LONG-distance running
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49100-8