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Current anti-obesity medications are only partly effective, due to substantial side effects, the temporary nature of the weight loss and the non-responsiveness of a considerable number of patients.
In a recently published series of studies led by TSRI Assistant Professor Anutosh Chakraborty of the Florida campus of The Scripps Research Institute (TSRI), scientists have identified a new therapeutic target -- a key protein that promotes fat accumulation in animal models by slowing the breakdown and expenditure of fat and encouraging weight gain.
[...] The expenditure of fat energy is preceded by a process called lipolysis that breaks down stored fat or triglycerides (specifically into free fatty acids and glycerol) to be used as energy in cells. The team discovered that deletion of IP6K1 affects interaction with another regulating protein and enhances the breakdown of fats.
To determine the therapeutic possibilities of the IP6K1 pathway, the team looked at the impact of an IP6K inhibitor known as TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl) purine] on diet-induced obesity in animal models. As it turns out, TNP significantly slows the initiation of diet-induced obesity and insulin resistance.
Journal References:
- Qingzhang Zhu, Sarbani Ghoshal, Ana Rodrigues, Su Gao, Alice Asterian, Theodore M. Kamenecka, James C. Barrow, Anutosh Chakraborty. Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis. Journal of Clinical Investigation, 2016; DOI: 10.1172/JCI85510
- Sarbani Ghoshal, Richa Tyagi, Qingzhang Zhu, Anutosh Chakraborty. Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis. The International Journal of Biochemistry & Cell Biology, 2016; 78: 149 DOI: 10.1016/j.biocel.2016.06.018
- Sarbani Ghoshal, Qingzhang Zhu, Alice Asteian, Hua Lin, Haifei Xu, Glen Ernst, James C. Barrow, Baoji Xu, Michael D. Cameron, Theodore M. Kamenecka, Anutosh Chakraborty. TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway. Molecular Metabolism, 2016; 5 (10): 903 DOI: 10.1016/j.molmet.2016.08.008
(Score: 2) by Post-Nihilist on Friday October 14 2016, @09:38PM
The synthesis in the last paper is full of small mistakes. Just in the first step there are at least 2 (bold number are mine)
To a solution of sodium 1 (1.65 g, 72 mmol, 1.36 equiv) in MeOH (100 mL) 2,6-dichloro-9H-purine 2 (10 g, 53 mmol, 1 equiv) was added under argon. The mixture was stirred to reflux for 6 h. The reaction was cooled to room temperature and stirred at room temperature overnight. Water (50 mL) was added and the mixture was neutralized with a solution of acetic acid. The precipitate was filtered, washed with water, and dried to afford the 2-chloro-6-methoxy-9H-purine as a white solid.
1-assuming they got the mmol right they meant NaOH not Na+
2- in 2,6-dichloro-9H-purine, the 9H is meaningless, worse it make related compound appers before the product used in the paper when you search for it. You have to rely on the molar weight to figure that they used 2,6-Dichloropurine and not 2,6-Dichloro-9-methyl-9H-purine.
Yay for peer review!! The reviewers should be ashamed that a nonpracticing amateur could see errors in a somewhat important section of the paper.
Be like us, be different, be a nihilist!!!
(Score: 0) by Anonymous Coward on Friday October 14 2016, @10:04PM
>"somewhat important section of the paper"
The methods section is not important to medical researchers. Try to publish some research in that area sometime and see. They will make you remove all the methods and math. If you are willing to delay publication and fight for it, you can put it in an appendix. It isn't a serious area of research, so don't be surprised when next time you spot check a paper you find the same/similar errors.
ps I have no idea if your critique is valid or not, but it sounds like it is coming from someone who *actually read the paper*.
(Score: 2) by Post-Nihilist on Saturday October 15 2016, @02:11AM
Try to publish some research in that area sometime and see.
I did¹... Then I became a nihilist.
Not that exact same area obviously and for privacy reasons I wont name the journals nor the papers
Be like us, be different, be a nihilist!!!