Upregulation of skeletal muscle PGC-1α through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance.
Regular exercise and physical training enhance physiological capacity and improve metabolic diseases. Skeletal muscles require peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in the process of their adaptation to exercise owing to PGC-1α's ability to regulate mitochondrial biogenesis, angiogenesis, and oxidative metabolism. Cyanidin-3-glucoside (Cy3G) is a natural polyphenol and a nutraceutical factor, which has several beneficial effects on human health. Here, the effect of Cy3G on exercise performance and the underlying mechanisms involved were investigated. ICR mice were given Cy3G (1 mg/kg, orally) everyday and made to perform weight-loaded swimming exercise for 15 days. The endurance of mice orally administered with Cy3G was improved, enabling them to swim longer (time) and while the levels of exercise-induced lactate and fatigue markers (urea nitrogen, creatinine and total ketone bodies) were reduced. Additionally, the expression of lactate metabolism-related genes (lactate dehydrogenase B and monocarboxylate transporter 1) in gastrocnemius and biceps femoris muscles was increased in response to Cy3G-induced PGC-1α upregulation. In vitro, using C2C12 myotubes, Cy3G-induced elevation of intracellular cyclic AMP levels increased PGC-1α expression via the Ca2+/calmodulin-dependent protein kinase kinase pathway. This study demonstrates that Cy3G enhances exercise performance by activating lactate metabolism through skeletal muscle PGC-1α upregulation.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.
Toshiya
T
Matsukawa
Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.
Hideko
H
Motojima
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.
Yuki
Y
Sato
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.
Shinya
S
Takahashi
Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.|Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.
Myra O
MO
Villareal
Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.|Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki 305-8572, Japan.
Hiroko
H
Isoda
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D005247:Feeding Behavior; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D013550:Swimming; D015854:Up-Regulation / Q000187:drug effects
D000872:Anthocyanins; D001786:Blood Glucose; D005960:Glucosides; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C462279:cyanidin-3-O-beta-glucopyranoside; D019344:Lactic Acid; D000242:Cyclic AMP; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D000263:Adenylate Kinase