title: De novo ceramides synthesis is not involved in skeletal muscle atrophy induced by short-term mechanical unloading.
abstract: Patients admitted to the intensive care unit commonly develop skeletal muscle weakness that can exacerbate illness and complicate their recovery. Beyond the primary disease or aging, weakness is promoted by a variety of prolonged hospitalization-associated conditions. These include altered nutritional status, pharmacologic side effects, physical inactivity, and prolonged bed rest. The two latter conditions (i.e. inactivity and bed rest) are the most ubiquitous, affecting all patients during a prolonged hospitalization. In both cases, skeletal muscle utilization is decreased with a concomitant reduction in fatty acid oxidation. Subsequent fatty acids accumulation converted to ceramides could be a cellular mechanism leading to muscle wasting. Indeed these sphingolipids act as second messengers in several of molecular signaling pathways involved in muscle atrophy. Consequently, the aim of this work is to determine the effects of immobilization on muscle ceramides accumulation, and identify the role of these ectopic lipids in molecular mechanisms involved in skeletal muscle atrophy. For this purpose, male Wistar rats were treated with an inhibitor of de novo synthesis of ceramides (i.e. myriocin) and subjected to hindlimb unloading for 7 days. We found that hindlimb unloading induced skeletal muscle atrophy, in part through proteolysis (i.e. decrease in AKT activation, increase in MuRF1 and polyubiquinated proteins content) and apoptosis activations (i.e. increase in Bax/Bcl-2 ratio and cleaved caspase-3). Myriocin treatment did not prevent skeletal muscle atrophy and concomitant induction of apoptosis and proteolysis. Data concerning muscle ceramides content are being analyzed. Together, these results suggest that de novo synthesis of ceramides is not involved in muscle atrophy induced by a short period of hindlimb unloading.
authors.affiliation: Laboratory Movement, Sport and health Sciences - M2S (University Rennes 2), UFR APS, France.
authors.forename: Erwann
authors.initials: E
authors.lastname: Salaun
authors.affiliation: Laboratory Movement, Sport and health Sciences - M2S (University Rennes 2), UFR APS, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Gratas-Delamarche
authors.affiliation: Laboratory Movement, Sport and health Sciences - M2S (University Rennes 2), UFR APS, France. Electronic address: frederic.derbre@univ-rennes2.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Derbré