Skeletal muscle-specific inducible AMPKα1/α2 knockout mice develop muscle weakness, glycogen depletion, and fibrosis that persists during disuse atrophy.
Am J Physiol Endocrinol Metab
; 326(1): E50-E60, 2024 01 01.
Article
em En
| MEDLINE
| ID: mdl-38019084
The 5' adenosine monophosphate-activated protein kinase (AMPK) is an important skeletal muscle regulator implicated as a possible therapeutic target to ameliorate the local undesired deconditioning of disuse atrophy. However, the muscle-specific role of AMPK in regulating muscle function, fibrosis, and transcriptional reprogramming during physical disuse is unknown. The purpose of this study was to determine how the absence of both catalytic subunits of AMPK in skeletal muscle influences muscle force production, collagen deposition, and the transcriptional landscape. We generated skeletal muscle-specific tamoxifen-inducible AMPKα1/α2 knockout (AMPKα-/-) mice that underwent 14 days of hindlimb unloading (HU) or remained ambulatory for 14 days (AMB). We found that AMPKα-/- during ambulatory conditions altered body weight and myofiber size, decreased muscle function, depleted glycogen stores and TBC1 domain family member 1 (TBC1D1) phosphorylation, increased collagen deposition, and altered transcriptional pathways. Primarily, pathways related to cellular senescence and mitochondrial biogenesis and function were influenced by the absence of AMPKα. The effects of AMPKα-/- persisted, but were not worsened, following hindlimb unloading. Together, we report that AMPKα is necessary to maintain skeletal muscle quality.NEW & NOTEWORTHY We determined that skeletal muscle-specific AMPKα knockout (KO) mice display functional, fibrotic, and transcriptional alterations before and during muscle disuse atrophy. We also observed that AMPKα KO drives muscle fibrosis and pathways related to cellular senescence that continues during the hindlimb unloading period.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos Musculares Atróficos
/
Proteínas Quinases Ativadas por AMP
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article