Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1785034930665816064 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10148119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT meadowsallisonm narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT hankim narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT singhkomudi narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT murgiaantonio narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT mcnallybend narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT westjamesa narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT huffstutlerrebeccad narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT powellwileytiffanym narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT baumeryvonne narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT griffinjulianl narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness AT sackmichaeln narachidonylglycineisacaloricstatedependentcirculatingmetabolitewhichregulateshumancd4tcellresponsiveness |