Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine was written by Niemann, Birte;Haufs-Brusberg, Saskia;Puetz, Laura;Feickert, Martin;Jaeckstein, Michelle Y.;Hoffmann, Anne;Zurkovic, Jelena;Heine, Markus;Trautmann, Eva-Maria;Mueller, Christa E.;Toenjes, Anke;Schlein, Christian;Jafari, Azin;Eltzschig, Holger K.;Gnad, Thorsten;Blueher, Matthias;Krahmer, Natalie;Kovacs, Peter;Heeren, Joerg;Pfeifer, Alexander. And the article was included in Nature (London, United Kingdom) in 2022.Safety of 2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one This article mentions the following:
Brown adipose tissue (BAT) dissipates energy and promotes cardiometabolic health. Loss of BAT during obesity and ageing is a principal hurdle for BAT-centered obesity therapies, but not much is known about BAT apoptosis. Here, untargeted metabolomics demonstrated that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched. This apoptotic secretome enhances expression of the thermogenic program in healthy adipocytes. This effect is mediated by the purine inosine that stimulates energy expenditure in brown adipocytes by the cyclic adenosine monophosphate-protein kinase A signalling pathway. Treatment of mice with inosine increased BAT-dependent energy expenditure and induced ′browning′ of white adipose tissue. Mechanistically, the equilibrative nucleoside transporter 1 (ENT1, SLC29A1) regulates inosine levels in BAT: ENT1-deficiency increases extracellular inosine levels and consequently enhances thermogenic adipocyte differentiation. In mice, pharmacol. inhibition of ENT1 as well as global and adipose-specific ablation enhanced BAT activity and counteracted diet-induced obesity, resp. In human brown adipocytes, knockdown or blockade of ENT1 increased extracellular inosine, which enhanced thermogenic capacity. Conversely, high ENT1 levels correlated with lower expression of the thermogenic marker UCP1 in human adipose tissues. Finally, the Ile216Thr loss of function mutation in human ENT1 was associated with significantly lower body mass index and 59% lower odds of obesity for individuals carrying the Thr variant. Our data identify inosine as a metabolite released during apoptosis with a ′replace me′ signalling function that regulates thermogenic fat and counteracts obesity. In the experiment, the researchers used many compounds, for example, 2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one (cas: 118-00-3Safety of 2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one).
2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one (cas: 118-00-3) belongs to tetrahydrofuran derivatives. Tetrahydrofuran (THF) is a Lewis base that bonds to a variety of Lewis acids such as I2, phenols, triethylaluminum and bis(hexafluoroacetylacetonato)copper(II). Commercial tetrahydrofuran contains substantial water that must be removed for sensitive operations, e.g. those involving organometallic compounds. Although tetrahydrofuran is traditionally dried by distillation from an aggressive desiccant, molecular sieves are superior.Safety of 2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem