N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+T cell responsiveness

• DOI: 10.1016/j.isci.2023.106578
• Publication Date: 2023-04-07T01:29:40Z
• Authors: Allison M. Meadows; Kim Han; Komudi Singh; Antonio Murgia; Ben D. McNally; James A. West; Rebecca D. Huffst...; Tiffany M. Powell...; Yvonne Baumer; Julian L. Griffin; Michael N. Sack
• Keywords: Caloric theory; Intermittent Fasting

Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic inflammatory disease. As a human model of deprivation, 24-h fast blunts innate adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers same immunomodulatory effects on transformed lines. To identify mediators orchestrating this, metabolomic lipidomic analysis was performed extracted after re-feeding. Bioinformatic integration with concurrent peripheral blood mononuclear cells RNA-seq implicated key metabolite-sensing GPCRs in fasting-mediated immunomodulation. The putative GPR18 ligand N-arachidonylglycine (NAGly) elevated during attenuated CD4+T via MTORC1 signaling. In parallel, NAGly reduced Th1 Th17 cytokines levels isolated from obese subjects, identifying fasting-responsive intermediate that may contribute regulation nutrient-level dependent inflammation associated