Am J Physiol Cell Physiol. 2025 Nov 21. doi: 10.1152/ajpcell.00695.2025. Online ahead of print.
ABSTRACT
It remains unclear how excess adipose tissue in obesity leads to inflammation, insulin resistance and other comorbidities. Extracellular nucleosides can induce inflammation through the activation of immune cell toll-like and purinergic receptors. The present study quantified nucleoside release from adipocytes and adipose tissue. Cultured mouse adipocytes released many nucleosides used in RNA/DNA. Adipose tissue from obese mice released more nucleosides than that from control non-obese mice ex vivo and had higher interstitial fluid concentrations in vivo. Consistent with the mouse study, human adipose tissue also showed significant release of adenosine/deoxyadenosine, guanosine/deoxyguanosine, and uridine ex vivo. Adipocytes release nucleosides in part through the equilibrative nucleoside transporter 1, though other pathways appear to also contribute to extracellular nucleoside concentrations. Extracellular nucleosides induce adipose tissue expression of inflammatory cytokines TNFα, IL-6, and IL-1β. These data uncover a previously unknown phenomenon of adipocyte release of nucleosides, which contribute to adipose tissue inflammation in obesity.
PMID:41269663 | DOI:10.1152/ajpcell.00695.2025
