Slc12a8 in the lateral hypothalamus maintains energy metabolism and skeletal muscle functions during aging.
Cell Rep
; 40(4): 111131, 2022 07 26.
Article
em En
| MEDLINE
| ID: mdl-35905718
ABSTRACT
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 ß2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-ß2-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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcopenia
/
Fragilidade
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article