The role of 5′-adenosine monophosphate-activated protein kinase(AMPK)in skeletal muscle atrophy

As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.

The skeletal muscle fiber periphery:A nexus of mTOR-related anabolism

Skeletal muscle anabolism is driven by numerous stimuli such as growth factors,nutrients(i.e.,amino acids,glucose),and mechanical stress.These stimuli are integrated by the mechanistic target of rapamycin(mTOR)complex 1(mTORC1)signal transduction cascade.In recent years,work from our laboratory and elsewhere has sought to unravel the molecular mechanisms underpinning the mTOR-related activation of muscle protein synthesis(MPS),as well as the spatial regulation of these mechanisms within the skeletal muscle cell.These studies have suggested that the skeletal muscle fiber periphery is a region of central importance in anabolism(i.e.,growth/MPS).Indeed,the fiber periphery is replete with the substrates,molecular machinery,and translational apparatus necessary to facilitate MPS.This review provides a summary of the mechanisms underpinning the mTOR-associated activation of MPS from cell,rodent,and human studies.It also presents an overview of the spatial regulation of mTORC1 in response to anabolic stimuli and outlines the factors that distinguish the periphery of the cell as a highly notable region of skeletal muscle for the induction of MPS.Future research should seek to further explore the nutrient-induced activation of mTORC1 at the periphery of skeletal muscle fibers.