| First Author | Ito N | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 4 | Pages | 111131 |
| PubMed ID | 35905718 | Mgi Jnum | J:333074 |
| Mgi Id | MGI:7329684 | Doi | 10.1016/j.celrep.2022.111131 |
| Citation | Ito N, et al. (2022) Slc12a8 in the lateral hypothalamus maintains energy metabolism and skeletal muscle functions during aging. Cell Rep 40(4):111131 |
| abstractText | Sarcopenia and frailty are urgent socio-economic problems worldwide. Here we demonstrate a functional connection between the lateral hypothalamus (LH) and skeletal muscle through Slc12a8, a recently identified nicotinamide mononucleotide transporter, and its relationship to sarcopenia and frailty. Slc12a8-expressing cells are mainly localized in the LH. LH-specific knockdown of Slc12a8 in young mice decreases activity-dependent energy and carbohydrate expenditure and skeletal muscle functions, including muscle mass, muscle force, intramuscular glycolysis, and protein synthesis. LH-specific Slc12a8 knockdown also decreases sympathetic nerve signals at neuromuscular junctions and beta2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-beta2-adrenergic receptor axis. LH-specific overexpression of Slc12a8 in aged mice significantly ameliorates age-associated decreases in energy expenditure and skeletal muscle functions. Our results highlight an important role of Slc12a8 in the LH for regulation of whole-body metabolism and skeletal muscle functions and provide insights into the pathogenesis of sarcopenia and frailty during aging. |
