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- Title
Targeted Disruption of AdipoR1 and R2 Caused Abrogation of Adiponectin Binding and Actions, Associated with Dysregulation of Glucose and Lipid Metabolism, Oxidative Stress and Inflammation.
- Authors
Yamauchi, Toshimasa; Kubota, Naoto; Iwabu, Masato; Hada, Yusuke; Ueki, Kohjiro; Tobe, Kazuyuki; Kadowaki, Takashi
- Abstract
The adipocyte-derived hormone adiponectin plays central roles as antidiabetic and antiatherogenic adipokine. AdipoR1 and R2 have been shown to serve as receptors for adiponectin in vitro, and their reduction in obesity appeared to be correlated with reduced adiponectin sensitivity. Here we show that adenovirus-mediated expression of AdipoR1 in liver of db/db mice increased adiponectin effects, such as increased AMPK activation, decreases in gluconeogenic enzymes and endogenous glucose production (EGP), and that of AdipoR2 activated PPARalpha pathways, including stimulation of fatty-acid oxidation and inhibition of inflammation and oxidative stress, both ameliorating diabetes. Targeted disruption of AdipoR1 resulted in abrogation of adiponectin-induced AMPK activation and increased EGP, whereas targeted disruption of AdipoR2 resulted in decreased PPARalpha activation and decreased glucose uptake. Targeted disruption of both AdipoR1 and R2 abolished adiponectin binding and adiponectin actions, and resulted in increased tissue triglyceride content, inflammation and oxidative stress, leading to insulin resistance and marked glucose intolerance. In conclusion, AdipoR1 and R2 serve as major receptors for adiponectin in vivo, and they play crucial roles in the regulation of glucose and lipid metabolism, inflammation and oxidative stress in vivo.
- Subjects
MUSCLE proteins; PROTEIN binding; BLOOD sugar; LIPID metabolism; OXIDATIVE stress; INFLAMMATION
- Publication
Diabetes, 2007, Vol 56, pA376
- ISSN
0012-1797
- Publication type
Article