Slc12a8 in the lateral hypothalamus maintains energy metabolism and skeletal muscle functions during aging
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. S...
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Veröffentlicht in: | Cell reports (Cambridge) 2022-07, Vol.40 (4), p.111131-111131, Article 111131 |
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Zusammenfassung: | 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 β2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-β2-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.
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•Slc12a8 in the LH regulates energy expenditure and skeletal muscle functions•The LH-skeletal muscle connection is mediated by the sympathetic nerve-β2AR axis•LH-specific knockdown of Slc12a8 recapitulates phenotypes in aged mice•LH-specific overexpression of Slc12a8 improves sarcopenia and frailty in aged mice
Ito et al. demonstrate that Slc12a8 in the lateral hypothalamus (LH) regulates activity-dependent energy expenditure and skeletal muscle functions through the sympathetic nerve-β2AR axis during aging. Overexpression of Slc12a8 in the LH improves age-associated sarcopenia and frailty in mice, suggesting that Slc12a8 could be an important target of anti-aging interventions. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2022.111131 |