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AdipoRon

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Chemical compound Pharmaceutical compound
AdipoRon
Clinical data
Routes of
administration		Oral
ATC code
  • None
Identifiers
IUPAC name
  • 2-(4-Benzoylphenoxy)-N-(1-benzylpiperidin-4-yl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC27H28N2O3
Molar mass428.532 g·mol
3D model (JSmol)
SMILES
  • C1CN(CCC1NC(=O)COC2=CC=C(C=C2)C(=O)C3=CC=CC=C3)CC4=CC=CC=C4

AdipoRon is a selective, orally active, synthetic small-molecule agonist of the adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2) (Kd = 1.8 μM and 3.1 μM, respectively). It activates AMPK and PPARα signaling and ameliorates insulin resistance, dyslipidemia, and glucose intolerance in db/db mice (an animal model for type II diabetes and obesity). Moreover, AdipoRon has been found to extend the lifespans of db/db mice fed a high-fat diet, as well as improve exercise endurance. The compound was discovered by Japanese researchers in 2013 via screening of a compound library, and is the first orally active, small-molecule agonist of the adiponectin receptors to be identified.

Adiponectin receptor agonists such as AdipoRon have attracted interest as potential therapies for obesity, diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and a panoply of other conditions. In addition, adiponectin has recently been elucidated to mediate the antidepressant, anxiolytic, and neurogenic effects of physical exercise. Dysregulation of adiponectin expression has also been implicated in the pathology of mood disorders, anxiety disorders, eating disorders, neurodegenerative disorders, and various other neuropsychiatric disorders. Also, it has been determined that exercise improves insulin resistance via activation of AdipoR1. As such, adiponectin receptor agonists are a highly interesting therapeutic target for a variety of different conditions. Moreover, it has been suggested they could potentially be used as a substitute for exercise to achieve similar physical and mental health benefits. In 2016, the University of Tokyo announced that it would launch an investigation into claims of fabrication of AdipoR1, AdipoR2, and AdipoRon identification data, as accused by an anonymous person/group called Ordinary_researchers.

References

  1. ^ Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, et al. (November 2013). "A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity". Nature. 503 (7477): 493–499. Bibcode:2013Natur.503..493O. doi:10.1038/nature12656. PMID 24172895. S2CID 4447039.
  2. ^ Holland WL, Scherer PE (December 2013). "Cell Biology. Ronning after the adiponectin receptors". Science. 342 (6165): 1460–1461. Bibcode:2013Sci...342.1460H. doi:10.1126/science.1249077. PMC 4084614. PMID 24357309.
  3. Okada-Iwabu M, Iwabu M, Ueki K, Yamauchi T, Kadowaki T (October 2015). "Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity". Diabetes & Metabolism Journal. 39 (5): 363–372. doi:10.4093/dmj.2015.39.5.363. PMC 4641965. PMID 26566493.
  4. Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, et al. (November 2014). "Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin". Proceedings of the National Academy of Sciences of the United States of America. 111 (44): 15810–15815. Bibcode:2014PNAS..11115810Y. doi:10.1073/pnas.1415219111. PMC 4226125. PMID 25331877.
  5. Nicolas S, Veyssière J, Gandin C, Zsürger N, Pietri M, Heurteaux C, et al. (July 2015). "Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin". Psychoneuroendocrinology. 57: 72–83. doi:10.1016/j.psyneuen.2015.03.017. PMID 25889841. S2CID 20252349.
  6. ^ Li A, Yau SY, Machado S, Yuan TF, So KF (2015). "Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise?". CNS & Neurological Disorders Drug Targets. 14 (9): 1129–1144. doi:10.2174/1871527315666151111125533. PMID 26556072.
  7. ^ Wędrychowicz A, Zając A, Pilecki M, Kościelniak B, Tomasik PJ (December 2014). "Peptides from adipose tissue in mental disorders". World Journal of Psychiatry. 4 (4): 103–111. doi:10.5498/wjp.v4.i4.103. PMC 4274582. PMID 25540725.
  8. Cho JK, Kim SU, Hong HR, Yoon JH, Kang HS (November 2015). "Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1". International Journal of Sports Medicine. 36 (13): e24–e30. doi:10.1055/s-0035-1559715. PMID 26528942. S2CID 23387523.
  9. Yau SY, Li A, Xu A, So KF (January 2015). "Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment?". Neural Regeneration Research. 10 (1): 7–9. doi:10.4103/1673-5374.150637. PMC 4357120. PMID 25788905.
  10. Normile D (30 September 2016). "University of Tokyo to investigate data manipulation charges against six prominent research groups". ScienceInsider.
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