Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

Steve S. Lancel (1) , Matthijs K.C. Hesselink (2) , Estelle Woldt (1) , Yves Rouillé (3) , Emilie Dorchies (1) , Stephane Delhaye (1) , Christian Duhem (1) , Quentin Thorel (1) , Alicia Mayeuf-Louchart (1) , Benoit Pourcet (1) , Valérie Montel (4) , Gert Schaart (2) , Nicolas Beton (5) , Florence Picquet (4) , Olivier Briand (1) , Jean‐pierre Salles (5) , Helene Duez (1) , Patrick Schrauwen (2) , Bruno Bastide (4) , Bernard Bailleul (1) , Bart Staels (1) , Yasmine Sebti (1)

1 RNMCD - Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011
2 Maastricht University [Maastricht]
3 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
4 URePSSS - Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488
5 CPTP - Centre de Physiopathologie Toulouse Purpan

Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2-/- mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.

Mots clés: Adaptor Proteins; Signal Transducing; Animals; Autophagy; Caloric Restriction; Cell Plasticity; Cells; Cultured; Energy Metabolism; Extracellular Signal-Regulated MAP Kinases; Female; Humans; MAP Kinase Signaling System; Male; Membrane Proteins; Mice; Mitochondria; Muscle Fibers; Fast-Twitch; Slow-Twitch; Muscle; Skeletal; Oxidative Stress; Phenotype; Phosphorylation; Physical Endurance; Physical Exertion; RNA; Messenger; Glucose metabolism; Metabolism; Muscle Biology; Skeletal muscle

Domaines: Sciences du Vivant [q-bio]

Steve S. Lancel, Matthijs K.C. Hesselink, Estelle Woldt, Yves Rouillé, Emilie Dorchies, et al.. Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity. JCI Insight, 2018, 3 (9), ⟨10.1172/jci.insight.98081⟩. ⟨hal-04397483⟩