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1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression
Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with typ...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614678/ https://www.ncbi.nlm.nih.gov/pubmed/37908738 http://dx.doi.org/10.7150/thno.84645 |
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author | Li, Peng Li, Ke Yuan, Wenhui Xu, Yuqi Li, Ping Wu, Ruan Han, Jingru Yin, Zhinan Lu, Ligong Gao, Yunfei |
author_facet | Li, Peng Li, Ke Yuan, Wenhui Xu, Yuqi Li, Ping Wu, Ruan Han, Jingru Yin, Zhinan Lu, Ligong Gao, Yunfei |
author_sort | Li, Peng |
collection | PubMed |
description | Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with type 2 diabetes. C57BL/6J mice were fed either a high-fat diet (HFD) or normal chow (NC). We performed phenotypical and functional analyses of immune cells using flow cytometry. Vitamin D receptor (VDR) knockout γδ T cells were constructed using Cas9-gRNA targeted approaches to identify 1α,25(OH)(2)D(3)/VDR signaling pathway-mediated transcriptional regulation of fructose-1,6-bisphosphatase (FBP1) in γδ T cells. Results: Serum vitamin D deficiency aggravates inflammation in circulating γδ T cells in type 2 diabetes patients. We defined a critical role for 1α,25(OH)(2)D(3) in regulating glycolysis metabolism, protecting against inflammation, and alleviating insulin resistance. Mechanistically, 1α,25(OH)(2)D(3)-VDR promoted FBP1 expression to suppress glycolysis in γδ T cells, thereby inhibiting Akt/p38 MAPK phosphorylation and reducing inflammatory cytokine production. Notably, therapeutic administration of 1α,25(OH)(2)D(3) restrained inflammation in γδ T cells and ameliorated systemic insulin resistance in obese mice. Conclusions: Collectively, these findings show that 1α,25(OH)(2)D(3) plays an important role in maintaining γδ T cell homeostasis by orchestrating metabolic programs, and is a highly promising target for preventing obesity, inflammation, and insulin resistance. |
format | Online Article Text |
id | pubmed-10614678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-106146782023-10-31 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression Li, Peng Li, Ke Yuan, Wenhui Xu, Yuqi Li, Ping Wu, Ruan Han, Jingru Yin, Zhinan Lu, Ligong Gao, Yunfei Theranostics Research Paper Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with type 2 diabetes. C57BL/6J mice were fed either a high-fat diet (HFD) or normal chow (NC). We performed phenotypical and functional analyses of immune cells using flow cytometry. Vitamin D receptor (VDR) knockout γδ T cells were constructed using Cas9-gRNA targeted approaches to identify 1α,25(OH)(2)D(3)/VDR signaling pathway-mediated transcriptional regulation of fructose-1,6-bisphosphatase (FBP1) in γδ T cells. Results: Serum vitamin D deficiency aggravates inflammation in circulating γδ T cells in type 2 diabetes patients. We defined a critical role for 1α,25(OH)(2)D(3) in regulating glycolysis metabolism, protecting against inflammation, and alleviating insulin resistance. Mechanistically, 1α,25(OH)(2)D(3)-VDR promoted FBP1 expression to suppress glycolysis in γδ T cells, thereby inhibiting Akt/p38 MAPK phosphorylation and reducing inflammatory cytokine production. Notably, therapeutic administration of 1α,25(OH)(2)D(3) restrained inflammation in γδ T cells and ameliorated systemic insulin resistance in obese mice. Conclusions: Collectively, these findings show that 1α,25(OH)(2)D(3) plays an important role in maintaining γδ T cell homeostasis by orchestrating metabolic programs, and is a highly promising target for preventing obesity, inflammation, and insulin resistance. Ivyspring International Publisher 2023-09-25 /pmc/articles/PMC10614678/ /pubmed/37908738 http://dx.doi.org/10.7150/thno.84645 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Li, Peng Li, Ke Yuan, Wenhui Xu, Yuqi Li, Ping Wu, Ruan Han, Jingru Yin, Zhinan Lu, Ligong Gao, Yunfei 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
title | 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
title_full | 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
title_fullStr | 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
title_full_unstemmed | 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
title_short | 1α,25(OH)(2)D(3) ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
title_sort | 1α,25(oh)(2)d(3) ameliorates insulin resistance by alleviating γδ t cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614678/ https://www.ncbi.nlm.nih.gov/pubmed/37908738 http://dx.doi.org/10.7150/thno.84645 |
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