title: Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.
abstract: Adiponectin is an anti-diabetic adipokine. Its receptors possess a seven-transmembrane topology with the amino terminus located intracellularly, which is the opposite of G-protein-coupled receptors. Here we provide evidence that adiponectin induces extracellular Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes. Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin. Suppression of AdipoR1 also resulted in decreased PGC-1alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.
authors.affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Iwabu
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Miki
authors.initials: M
authors.lastname: Okada-Iwabu
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Funata
authors.forename: Mamiko
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Namiki
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakayama
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Tabata
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ogata
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Iseki
authors.initials: I
authors.lastname: Takamoto
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamauchi
authors.forename: Hironori
authors.initials: H
authors.lastname: Waki
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Kumpei
authors.initials: K
authors.lastname: Tokuyama
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Ueki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hirose
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kazushige
authors.initials: K
authors.lastname: Touhara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D054419:Receptors, Adiponectin / Q000172:deficiency / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014982:Xenopus laevis
chemical_list: D052242:Adiponectin; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D054419:Receptors, Adiponectin; D015534:Trans-Activators; D014157:Transcription Factors; C475419:adiponectin receptor 1, mouse; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose; D002118:Calcium