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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...

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Autores principales: Li, Peng, Li, Ke, Yuan, Wenhui, Xu, Yuqi, Li, Ping, Wu, Ruan, Han, Jingru, Yin, Zhinan, Lu, Ligong, Gao, Yunfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
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.
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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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