Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity
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Obesity associated with unhealthy diet and lack of exercise is shown to contribute to the onset and/or aggravation of the metabolic syndrome and diabetes, thus placing affected individuals at increased risk of cardiovascular disease and cancer. Plasma adiponectin levels are decreased in obesity, which causes insulin resistance and diabetes. Therefore, we identified adiponectin receptors (AdipoRs) as the therapeutic target. It was suggested that, similarly to caloric restriction and exercise, activation of the AdipoRs may have the potential not only to improve lifestyle-related diseases but to contribute to prolonged the shortened lifespan on a high caloric unhealthy diet. To this end, we have identified "AdipoRon" as an adiponectin receptor agonist. Indeed, AdipoRon ameliorated diabetes associated with obesity as well as to increase exercise endurance, thus prolonging shortened lifespan of obese mice fed on a high fat diet. Additionally, we have recently determined the crystal structures of the human AdipoRs. The seven-transmembrane helices of AdipoRs are structurally distinct from those of G-protein coupled receptors. It is expected that these findings will contribute not only to the elucidation of the AdipoR-related signal transduction but to the development and optimization of AdipoR-targeted therapeutics for obesity-related diseases such as diabetes.
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AdipoRon could prolong the lifespan of obese treated mice.
“It could even prolong the lifespan of obese treated mice [105,106].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [105]
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Compendious Review on Adipokines of Corpulence
Rada, F. H. (2022) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2022.00724 · Cited by 2 · see citing works
AdipoRon Effect on Expression of Lipid Metabolism Genes in Cultured Human Primary Macrophages
Pobozheva, I. A., Dracheva, K. V., Пчелина, С. Н., & Мирошникова, В. В. (2023) · Molecular Biology · doi:10.1134/s0026893323040143 · Cited by 2 · see citing works
Potential Role of Adiponectin Receptor Agonist, AdipoRon in Cardiometabolic Disease
Cho, E., & Lee, S. (2019) · Exercise Science · doi:10.15857/ksep.2019.28.2.102 · Cited by 1 · see citing works
The Effect of Adiporon on Lipid Metabolism Genes Expression in Human Macrophages
Pobozheva, I. A., Dracheva, K. V., Пчелина, С. Н., & Мирошникова, В. В. (2023) · Molecular Biology · doi:10.31857/s0026898423040183 · Cited by 1 · see citing works
Adiponectin-Based Therapeutics for Cancer Treatment
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Lindarto, D., Sazli, B. I., Syafril, S., & Saragih, A. (2020) · Journal of Endocrinology Tropical Medicine and Infectiouse Disease (JETROMI) · doi:10.32734/jetromi.v2i4.5025
Lee, C. Y. (2026) · Medicinal Chemistry Research · doi:10.1007/s00044-026-03577-8
- Authors
- Okada-Iwabu, M., Iwabu, M., Ueki, K., Yamauchi, T., & Kadowaki, T.
- Affiliations
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Japan Science and Technology Agency (JP)
- National Center for Global Health and Medicine (JP)
- The University of Tokyo (JP)
- Corresponding author
- Ueki, Kohjiro
- Yamauchi, Toshimasa
- Kadowaki, Takashi
- Venue
- Diabetes & Metabolism Journal
- Publisher
- Korean Diabetes Association
- Published
- 2015
- Volume
- 39
- Issue
- 5
- Pages
- 363
- ISSN
- 2233-6079 (ISSN-L)
- 2233-6087
- PMC
- PMC4641965
- OpenAlex
- W2099544095
- Cited by
- 60
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 12 · 2018: 4 · 2017: 7 · 2016: 9
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Diabetes & Metabolism Journal (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Education, Culture, Sports, Science, and Technology
- Japan Science and Technology Agency
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adiponectin receptors, AdipoRon, small molecule agonists, type 2 diabetes, obesity, lifespan extension, high-fat diet, insulin resistance, metabolic syndrome, crystal structure, seven transmembrane helices, exercise endurance, G protein-coupled receptors
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