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.
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AdipoR1 and AdipoR2 are the major adiponectin receptors in vivo.
“AdipoR1 and AdipoR2 are the major adiponectin receptors in vivo [9].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [9]
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- Authors
- Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., Ito, Y., Kamon, J., Tsuchida, A., Kumagai, K., Kozono, H., Hada, Y., Ogata, H., Tokuyama, K., Tsunoda, M., Ide, T., Murakami, K., Awazawa, M., Takamoto, I., Froguel, P., Hara, K., Tobe, K., Nagai, R., Ueki, K., & Kadowaki, T.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- University of Tsukuba (JP)
- Hammersmith Hospital (GB)
- Corresponding author
- Kadowaki, Takashi
- ORCID
- Venue
- Nature Medicine
- Published
- 2007-02-01
- Volume
- 13
- Issue
- 3
- Pages
- 332-339
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2134100055
- Cited by
- 1,396
- References
- 43
- Citations by year
- 2026: 29 · 2025: 56 · 2024: 63 · 2023: 62 · 2022: 60 · 2021: 81 · 2020: 69 · 2019: 62 · 2018: 77 · 2017: 72 · 2016: 77 · 2015: 83 · 2014: 66 · 2013: 104 · 2012: 87
- FWCI
- 58.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adiponectin, AdipoR1, AdipoR2, adiponectin receptors, AMPK, gluconeogenesis, fatty acid oxidation, insulin resistance, impaired glucose tolerance, adipose tissue inflammation, oxidative stress, adipokines, lipid metabolism
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Experimental, Female, Male, Mice, Inbred C57BL, Mice, Obese, Protein Binding, Receptors, Cell Surface, Mice, Knockout, Gene Targeting, Lipid Metabolism, Mice, Adiponectin, Receptors, Leptin, Receptors, Adiponectin
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