Chemistry:AdipoRon
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| Routes of administration | Oral |
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| Formula | C27H28N2O3 |
| Molar mass | 428.532 g·mol−1 |
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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).[1][2] 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).[1][2] Moreover, AdipoRon has been found to extend the lifespans of db/db mice fed a high-fat diet, as well as improve exercise endurance.[1][2][3] 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.[1][2]
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.[1][2] In addition, adiponectin has recently been elucidated to mediate the antidepressant, anxiolytic, and neurogenic effects of physical exercise.[4][5][6] 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.[7] Also, it has been determined that exercise improves insulin resistance via activation of AdipoR1.[8] As such, adiponectin receptor agonists are a highly interesting therapeutic target for a variety of different conditions.[1][2][6][7] Moreover, it has been suggested they could potentially be used as a substitute for exercise to achieve similar physical and mental health benefits.[1][2][6][9] 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.[10]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity". Nature 503 (7477): 493–499. November 2013. doi:10.1038/nature12656. PMID 24172895. Bibcode: 2013Natur.503..493O.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Cell Biology. Ronning after the adiponectin receptors". Science 342 (6165): 1460–1461. December 2013. doi:10.1126/science.1249077. PMID 24357309. Bibcode: 2013Sci...342.1460H.
- ↑ "Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity". Diabetes & Metabolism Journal 39 (5): 363–372. October 2015. doi:10.4093/dmj.2015.39.5.363. PMID 26566493.
- ↑ "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. November 2014. doi:10.1073/pnas.1415219111. PMID 25331877. Bibcode: 2014PNAS..11115810Y.
- ↑ "Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin". Psychoneuroendocrinology 57: 72–83. July 2015. doi:10.1016/j.psyneuen.2015.03.017. PMID 25889841.
- ↑ 6.0 6.1 6.2 "Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise?". CNS & Neurological Disorders Drug Targets 14 (9): 1129–1144. 2015. doi:10.2174/1871527315666151111125533. PMID 26556072.
- ↑ 7.0 7.1 "Peptides from adipose tissue in mental disorders". World Journal of Psychiatry 4 (4): 103–111. December 2014. doi:10.5498/wjp.v4.i4.103. PMID 25540725.
- ↑ "Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1". International Journal of Sports Medicine 36 (13): e24–e30. November 2015. doi:10.1055/s-0035-1559715. PMID 26528942.
- ↑ "Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment?". Neural Regeneration Research 10 (1): 7–9. January 2015. doi:10.4103/1673-5374.150637. PMID 25788905.
- ↑ "University of Tokyo to investigate data manipulation charges against six prominent research groups". ScienceInsider. 30 September 2016. https://www.science.org/content/article/university-tokyo-investigate-data-manipulation-charges-against-six-prominent-research.
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