Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions
| Autor: | Takeshi Takazawa, Ryozo Nagai, Hitomi Ogata, Philippe Froguel, Masato Iwabu, Tomohiro Ide, Miki Okada-Iwabu, Tetsuya Kubota, Hideki Kozono, Kazuyuki Tobe, Iseki Takamoto, Yasunori Nio, Atsushi Tsuchida, Yusuke Hada, Masaki Tsunoda, Yusuke Ito, Junji Kamon, Kazuo Hara, Masaki Kobayashi, Toshiyuki Maki, Motoharu Awazawa, Kumpei Tokuyama, Kohjiro Ueki, Katsuyoshi Kumagai, Toshimasa Yamauchi, Naoto Kubota, Kouji Murakami, Sachiko Kawamoto, Takashi Kadowaki |
|---|---|
| Přispěvatelé: | Information génomique et structurale (IGS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Section of Genomic Medicine, Imperial College London, Genome Centre, Imperial College London-Hammersmith campus |
| Rok vydání: | 2006 |
| Předmět: |
Blood Glucose
Male Peroxisome proliferator-activated receptor Mice Obese MESH: Gene Targeting MESH: Mice Knockout chemistry.chemical_compound Mice 0302 clinical medicine MESH: Diabetes Mellitus Experimental MESH: Animals MESH: Mice Obese MESH: Receptors Cell Surface MESH: Lipid Metabolism chemistry.chemical_classification Adiponectin receptor 1 Mice Knockout 0303 health sciences Adiponectin receptor 2 General Medicine MESH: Adiponectin AdipoRon Gene Targeting Receptors Leptin Female Adiponectin Receptors Adiponectin Protein Binding medicine.medical_specialty Adipokine 030209 endocrinology & metabolism Receptors Cell Surface Biology General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental 03 medical and health sciences MESH: Mice Inbred C57BL Internal medicine medicine MESH: Protein Binding Animals MESH: Mice 030304 developmental biology AMPK Lipid Metabolism MESH: Male Mice Inbred C57BL Endocrinology chemistry [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics MESH: Blood Glucose Adiponectin binding MESH: Female |
| Zdroj: | Nature Medicine Nature Medicine, Nature Publishing Group, 2007, 13 (3), pp.332-9. ⟨10.1038/nm1557⟩ Nature Medicine, 2007, 13 (3), pp.332-9. ⟨10.1038/nm1557⟩ |
| ISSN: | 1078-8956 1744-7933 |
| DOI: | 10.1038/nm1557⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|