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

Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time p...

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Autores principales: Meadows, Allison M., Han, Kim, Singh, Komudi, Murgia, Antonio, McNally, Ben D., West, James A., Huffstutler, Rebecca D., Powell-Wiley, Tiffany M., Baumer, Yvonne, Griffin, Julian L., Sack, Michael N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148119/
https://www.ncbi.nlm.nih.gov/pubmed/37128607
http://dx.doi.org/10.1016/j.isci.2023.106578
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author Meadows, Allison M.
Han, Kim
Singh, Komudi
Murgia, Antonio
McNally, Ben D.
West, James A.
Huffstutler, Rebecca D.
Powell-Wiley, Tiffany M.
Baumer, Yvonne
Griffin, Julian L.
Sack, Michael N.
author_facet Meadows, Allison M.
Han, Kim
Singh, Komudi
Murgia, Antonio
McNally, Ben D.
West, James A.
Huffstutler, Rebecca D.
Powell-Wiley, Tiffany M.
Baumer, Yvonne
Griffin, Julian L.
Sack, Michael N.
author_sort Meadows, Allison M.
collection PubMed
description Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers these same immunomodulatory effects on transformed cell lines. To identify serum mediators orchestrating this, metabolomic and lipidomic analysis was performed on serum extracted after a 24-h fast and re-feeding. Bioinformatic integration with concurrent peripheral blood mononuclear cells RNA-seq analysis implicated key metabolite-sensing GPCRs in fasting-mediated immunomodulation. The putative GPR18 ligand N-arachidonylglycine (NAGly) was elevated during fasting and attenuated CD4(+)T cell responsiveness via GPR18 MTORC1 signaling. In parallel, NAGly reduced inflammatory Th1 and Th17 cytokines levels in CD4(+)T cells isolated from obese subjects, identifying a fasting-responsive metabolic intermediate that may contribute to the regulation of nutrient-level dependent inflammation associated with metabolic disease.
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spelling pubmed-101481192023-04-30 N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness Meadows, Allison M. Han, Kim Singh, Komudi Murgia, Antonio McNally, Ben D. West, James A. Huffstutler, Rebecca D. Powell-Wiley, Tiffany M. Baumer, Yvonne Griffin, Julian L. Sack, Michael N. iScience Article Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers these same immunomodulatory effects on transformed cell lines. To identify serum mediators orchestrating this, metabolomic and lipidomic analysis was performed on serum extracted after a 24-h fast and re-feeding. Bioinformatic integration with concurrent peripheral blood mononuclear cells RNA-seq analysis implicated key metabolite-sensing GPCRs in fasting-mediated immunomodulation. The putative GPR18 ligand N-arachidonylglycine (NAGly) was elevated during fasting and attenuated CD4(+)T cell responsiveness via GPR18 MTORC1 signaling. In parallel, NAGly reduced inflammatory Th1 and Th17 cytokines levels in CD4(+)T cells isolated from obese subjects, identifying a fasting-responsive metabolic intermediate that may contribute to the regulation of nutrient-level dependent inflammation associated with metabolic disease. Elsevier 2023-04-06 /pmc/articles/PMC10148119/ /pubmed/37128607 http://dx.doi.org/10.1016/j.isci.2023.106578 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Meadows, Allison M.
Han, Kim
Singh, Komudi
Murgia, Antonio
McNally, Ben D.
West, James A.
Huffstutler, Rebecca D.
Powell-Wiley, Tiffany M.
Baumer, Yvonne
Griffin, Julian L.
Sack, Michael N.
N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness
title N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness
title_full N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness
title_fullStr N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness
title_full_unstemmed N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness
title_short N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4(+)T cell responsiveness
title_sort n-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human cd4(+)t cell responsiveness
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148119/
https://www.ncbi.nlm.nih.gov/pubmed/37128607
http://dx.doi.org/10.1016/j.isci.2023.106578
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