Journal Article

Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions

Murakami, Kouji, Kobayashi, Masaki, Kamon, Junji, Tsunoda, Masaki, Awazawa, Motoharu, Nagai, Ryozo, Kozono, Hideki, Maki, Toshiyuki, Tsuchida, Atsushi, Kubota, Naoto, Yamauchi, Toshimasa, Hara, Kazuo, Ide, Tomohiro, Kadowaki, Takashi, Takazawa, Takeshi, Ogata, Hitomi, Kubota, Tetsuya, Ito, Yusuke, Ueki, Kohjiro, Takamoto, Iseki, Tokuyama, Kumpei, Kumagai, Katsuyoshi, Nio, Yasunori, Tobe, Kazuyuki, Okada-Iwabu, Miki, Kawamoto, Sachiko, Iwabu, Masato, Froguel, Philippe, Hada, Yusuke

2007

Overview

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)-α 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-α 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 .

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adiponectin / Adiponectin - antagonists & inhibitors / Adiponectin - metabolism / Animals / Binding sites / Biomedical and Life Sciences / Biomedicine / Blood Glucose / Blood Glucose - metabolism / Cancer Research / Diabetes / Diabetes Mellitus, Experimental / Diabetes Mellitus, Experimental - genetics / Diabetes Mellitus, Experimental - metabolism / Fatty acids / Female / Gene expression / Gene Targeting / Genetics / Human genetics / Infectious Diseases / Kinases / Life Sciences / Lipid Metabolism / Lipid Metabolism - genetics / Male / Metabolic Diseases / Metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / Mice, Obese / Molecular Medicine / Neurosciences / Obesity / Oxidation / Oxidative stress / Protein Binding / Protein Binding - genetics / Receptors, Adiponectin / Receptors, Cell Surface / Receptors, Cell Surface - antagonists & inhibitors / Receptors, Cell Surface - deficiency / Receptors, Cell Surface - genetics / Receptors, Cell Surface - metabolism / Receptors, Leptin