TY - JOUR
T1 - Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity
AU - Lancel, Steve
AU - Hesselink, Matthijs K. C.
AU - Woldt, Estelle
AU - Rouille, Yves
AU - Dorchies, Emilie
AU - Delhaye, Stephane
AU - Duhem, Christian
AU - Thorel, Quentin
AU - Mayeuf-Louchart, Alicia
AU - Pourcet, Benoit
AU - Montel, Valerie
AU - Schaart, Gert
AU - Beton, Nicolas
AU - Picquet, Florence
AU - Briand, Olivier
AU - Salles, Jean Pierre
AU - Duez, Helene
AU - Schrauwen, Patrick
AU - Bastide, Bruno
AU - Bailleul, Bernard
AU - Staels, Bart
AU - Sebti, Yasmine
PY - 2018/5/3
Y1 - 2018/5/3
N2 - 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.
AB - 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.
KW - ELECTRON-TRANSPORT CHAIN
KW - ACTIVATED PROTEIN-KINASE
KW - MITOCHONDRIAL BIOGENESIS
KW - PERMEABILITY TRANSITION
KW - PHENOTYPIC ANALYSIS
KW - AUTOPHAGY
KW - EXERCISE
KW - MOUSE
KW - STAT3
KW - ERK
U2 - 10.1172/jci.insight.98081
DO - 10.1172/jci.insight.98081
M3 - Article
C2 - 29720572
SN - 2379-3708
VL - 3
SP - 1
EP - 13
JO - JCI INSIGHT
JF - JCI INSIGHT
IS - 9
M1 - e98081
ER -