Skeletal muscle-specific inducible AMPK α1/α2 knockout mice develop muscle weakness, glycogen depletion, and fibrosis that persists during disuse atrophy

Am J Physiol Endocrinol Metab. 2023 Nov 29. doi: 10.1152/ajpendo.00261.2023. Online ahead of print.ABSTRACTThe 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 are unknown. The purpose of this study was to determine how the absence of both catalytic subunits of AMPK in skeletal muscle influence muscle force production, collagen deposition, and the transcriptional landscape. We generated skeletal muscle-specific tamoxifen inducible AMPKα1/α2 knock out (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.PMID:38019084 | DOI:10.1152/ajpendo.00261.2023
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Source Type: research