title: Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions.
abstract: Adiponectin plays a central role as an antidiabetic and antiatherogenic adipokine. AdipoR1 and AdipoR2 serve as receptors for adiponectin in vitro, and their reduction in obesity seems to be correlated with reduced adiponectin sensitivity. Here we show that adenovirus-mediated expression of AdipoR1 and R2 in the liver of Lepr(-/-) mice increased AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor (PPAR)-alpha signaling pathways, respectively. Activation of AMPK reduced gluconeogenesis, whereas expression of the receptors in both cases increased fatty acid oxidation and lead to an amelioration of diabetes. Alternatively, targeted disruption of AdipoR1 resulted in the abrogation of adiponectin-induced AMPK activation, whereas that of AdipoR2 resulted in decreased activity of PPAR-alpha signaling pathways. Simultaneous disruption of both AdipoR1 and R2 abolished adiponectin binding and actions, resulting in increased tissue triglyceride content, inflammation and oxidative stress, and thus leading to insulin resistance and marked glucose intolerance. Therefore, AdipoR1 and R2 serve as the predominant receptors for adiponectin in vivo and play important roles in the regulation of glucose and lipid metabolism, inflammation and oxidative stress in vivo.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nio
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maki
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takazawa
authors.forename: Masato
authors.initials: M
authors.lastname: Iwabu
authors.forename: Miki
authors.initials: M
authors.lastname: Okada-Iwabu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kubota
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.forename: Junji
authors.initials: J
authors.lastname: Kamon
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Kumagai
authors.forename: Hideki
authors.initials: H
authors.lastname: Kozono
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hada
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ogata
authors.forename: Kumpei
authors.initials: K
authors.lastname: Tokuyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ide
authors.forename: Kouji
authors.initials: K
authors.lastname: Murakami
authors.forename: Motoharu
authors.initials: M
authors.lastname: Awazawa
authors.forename: Iseki
authors.initials: I
authors.lastname: Takamoto
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Ueki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D011485:Protein Binding / Q000235:genetics; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D054411:Receptors, Leptin
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse