Pleiotropic effects of sphingolipids in skeletal muscle

Abstract

Studies of the last two decades have demonstrated that sphingolipids are important signalling molecules exerting key roles in the control of fundamental biological processes including proliferation, differentiation, motility and survival. Here we review the role of bioactive sphingolipids such as ceramide, sphingosine, sphingosine 1-phosphate, ganglioside GM3, in the regulation of skeletal muscle biology. The emerging picture is in favour of a complex role of these molecules, which appear implicated in the activation of muscle resident stem cells, their proliferation and differentiation, finalized at skeletal muscle regeneration. Moreover, they are involved in the regulation of contractile properties, tissue responsiveness to insulin and muscle fiber trophism. Hopefully, this article will provide a framework for future investigation into the field, aimed at establishing whether altered sphingolipid metabolism is implicated in the onset of skeletal muscle diseases and identifying new pharmacological targets for the therapy of multiple illnesses, including muscular dystrophies and diabetes.

Sphingosine Kinase 1 Is Regulated by Peroxisome Proliferator-activated Receptor α in Response to Free Fatty Acids and Is Essential for Skeletal Muscle Interleukin-6 Production and Signaling in Diet-induced Obesity

“…Thus, we propose that in the context of obesity, myotubes may sense damage due to steatosis, increased oxidative stress, or other metabolic disruptions, which may increase IL-6 production to initiate repair mechanisms, and SphK1 may play a role in this process. This notion is consistent with other studies that suggest roles for SphK1 in muscle regeneration (99). Thus, it is still undetermined whether the function of S1P-induced IL-6 plays a pathological role in this context, or rather, a response to repair muscle damage that may occur in obesity.…”

Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity

“…SPH serves as the metabolic precursor for S1P, a potent lipid signaling molecule with several well-defi ned cellular activities key for skeletal muscle development, repair, and function ( 44,45 ). LC/MS measurements of SPH indicated levels of this compound remained stable in response to each treatment.…”

Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila

“…This presumably occurs through inter-compartmental movement of S1P via a transporter such as SPNS2, a member of the major facilitator family of transporters that has been shown to specifically transport S1P (Osborne et al, 2008;Kawahara et al, 2009;Hisano et al, 2011). S1P has been implicated in muscle repair and satellite cell proliferation and myoblast differentiation in vitro (Nagata et al, 2006;Bruni and Donati, 2008;Rapizzi et al, 2008). Here, we show that, in Drosophila, wunen reduction, in addition to suppressing the wing vein defect, also suppresses dystrophic muscle defects as assayed by muscle integrity, Projectin (Bent -FlyBase) protein localization in sarcomeres, and fly movement over time.…”