Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance
In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR in vivo, and verified...
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Frontiers Media S.A.
2022-07-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.927272/full |
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author | Chenzhe Gao Chenzhe Gao Marwa Yagoub Farag Koko Mingxing Ding Weichen Hong Jianping Li Na Dong Mizhou Hui |
author_facet | Chenzhe Gao Chenzhe Gao Marwa Yagoub Farag Koko Mingxing Ding Weichen Hong Jianping Li Na Dong Mizhou Hui |
author_sort | Chenzhe Gao |
collection | DOAJ |
description | In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR in vivo, and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation in vitro. Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice. We found that an IAP + IAP enhancer significantly ameliorated blood glucose, insulin, low-density lipoprotein, gut barrier function, inflammatory markers, and lipopolysaccharide (LPS) in serum. IAP could dephosphorylate LPS and nucleoside triphosphate in a pH-dependent manner in vitro. Firstly, LPS is inactivated by IAP and IAP reduces LPS-induced inflammation. Secondly, adenosine, a dephosphorylated product of adenosine triphosphate, elicited anti-inflammatory effects by binding to the A2A receptor, which inhibits NF-κB, TNF, and PI3K-Akt signalling pathways. Hence, IAP can be used as a natural anti-inflammatory agent to reduce intestinal inflammation-induced IR. |
first_indexed | 2024-04-13T20:18:41Z |
format | Article |
id | doaj.art-e2718335591049eb91adc02ef47a2158 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-13T20:18:41Z |
publishDate | 2022-07-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-e2718335591049eb91adc02ef47a21582022-12-22T02:31:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.927272927272Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistanceChenzhe Gao0Chenzhe Gao1Marwa Yagoub Farag Koko2Mingxing Ding3Weichen Hong4Jianping Li5Na Dong6Mizhou Hui7The Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, ChinaCollege of Food, Northeast Agricultural University, Harbin, ChinaCollege of Food, Northeast Agricultural University, Harbin, ChinaChangchun Jiahe Surgery Hospital, Changchun, ChinaThe Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, ChinaCollege of Food, Northeast Agricultural University, Harbin, ChinaThe Laboratory of Molecular Nutrition and Immunity, Institute of Animal Nutrition, Northeast Agricultural University, Harbin, ChinaCollege of Food, Northeast Agricultural University, Harbin, ChinaIn this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR in vivo, and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation in vitro. Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice. We found that an IAP + IAP enhancer significantly ameliorated blood glucose, insulin, low-density lipoprotein, gut barrier function, inflammatory markers, and lipopolysaccharide (LPS) in serum. IAP could dephosphorylate LPS and nucleoside triphosphate in a pH-dependent manner in vitro. Firstly, LPS is inactivated by IAP and IAP reduces LPS-induced inflammation. Secondly, adenosine, a dephosphorylated product of adenosine triphosphate, elicited anti-inflammatory effects by binding to the A2A receptor, which inhibits NF-κB, TNF, and PI3K-Akt signalling pathways. Hence, IAP can be used as a natural anti-inflammatory agent to reduce intestinal inflammation-induced IR.https://www.frontiersin.org/articles/10.3389/fimmu.2022.927272/fullintestinal inflammationintestinal alkaline phosphataselipopolysaccharideadenosinedephosphorylationsignalling pathway |
spellingShingle | Chenzhe Gao Chenzhe Gao Marwa Yagoub Farag Koko Mingxing Ding Weichen Hong Jianping Li Na Dong Mizhou Hui Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance Frontiers in Immunology intestinal inflammation intestinal alkaline phosphatase lipopolysaccharide adenosine dephosphorylation signalling pathway |
title | Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance |
title_full | Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance |
title_fullStr | Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance |
title_full_unstemmed | Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance |
title_short | Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance |
title_sort | intestinal alkaline phosphatase iap iap enhancer attenuates intestinal inflammation and alleviates insulin resistance |
topic | intestinal inflammation intestinal alkaline phosphatase lipopolysaccharide adenosine dephosphorylation signalling pathway |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.927272/full |
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