Adipocyte release of nucleosides contributes to obesity-associated inflammation

Obese adipose tissue drives inflammation through several mechanisms. Extracellular nucleosides can induce macrophage inflammation through the activation of 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, resulting in higher interstitial fluid concentrations. 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 (ENT1), and this release induces macrophage TNFα and IL-1β expression. Treatment of mice with the ENT1 inhibitor in vivo increased adipose tissue interstitial nucleoside concentrations and cytokine expression. These data uncover a previously unknown phe..., , , # Adipocyte release of nucleosides contributes to obesity-associated inflammation

Dataset DOI: [10.5061/dryad.bk3j9kdp3](https://doi.org/10.5061/dryad.bk3j9kdp3)

## Description of the data and file structure

Cells were cultured in various conditions, and nucleoside release was quantified by LC-MS/MS-MRM. Mouse and human adipose tissue explants were cultured in a PDSM flow chamber, and nucleoside release was quantified in the effluent. Expression of nucleoside transporter ENT1 was quantified by qPCR and Western blot in human adipose tissue. Mice were treated with the ENT1 inhibitor, and adipose tissue interstitial fluid collected for measure of nucleoside concentration. Adipose tissue was also collected for cytokine expression. Murine macrophages were treated with adipocyte conditioned media or guanosine and cytokine expression quantified with qPCR

### Files and variables

#### File: Fig_1A_3T3.csv

**Description:** 3T3-L1 fibroblasts and adipocytes were cultured and media release of..., Subjects undergoing procedures at UCLA signed consent to allow any remnant specimens to be de-identified and used in research. Identifying data was not attached to these remnants, which were distributed in a de-identified manner.