Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes

Abstract Backgroud Hypoadiponectinemia is the important cause of insulin resistance. Recent studies have shown that periodontitis is associated with hypoadiponectinemia. The purpose of this study was to investigate the effect of periodontitis-induced endoplasmic reticulum stress (ERS) in visceral ad...

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Main Authors: Qianqi Wu, Li Yan, Xiao Wu, Yiyan Chen, Leilei Ye, Yingtao Lv, Yuan Su
Format: Article
Language:English
Published: BMC 2023-12-01
Series:BMC Oral Health
Subjects:
Online Access:https://doi.org/10.1186/s12903-023-03758-6
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author Qianqi Wu
Li Yan
Xiao Wu
Yiyan Chen
Leilei Ye
Yingtao Lv
Yuan Su
author_facet Qianqi Wu
Li Yan
Xiao Wu
Yiyan Chen
Leilei Ye
Yingtao Lv
Yuan Su
author_sort Qianqi Wu
collection DOAJ
description Abstract Backgroud Hypoadiponectinemia is the important cause of insulin resistance. Recent studies have shown that periodontitis is associated with hypoadiponectinemia. The purpose of this study was to investigate the effect of periodontitis-induced endoplasmic reticulum stress (ERS) in visceral adipocytes on hypoadiponectinemia. Methods Rat periodontitis models were established by local ligation with silk around the bilateral maxillary second molars. Porphyromonas gingivalis-lipopolysaccharid (P.g-LPS) was also used to stimulate the visceral adipocytes in vitro. The protein expression levels of glucose regulated protein 78 (GRP78), inositol-requiring protein 1α (IRE1α), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and adiponectin were detected. IRE1α lentiviruses were transfected into visceral adipocytes in vitro, and an IRE1α inhibitor (KIRA6) was injected in epididymal adipose tissue of rats to detect and verify the effect of ERS on adiponectin expression in visceral adipocytes in vivo. Results Hypoadiponectinemia was observed in periodontitis rat, and the expression levels of ERS key proteins GRP78 and the phosphorylation levels of IRE1α (p-IRE1α)/IRE1α in visceral adipocytes were increased, while the expression levels of adiponectin protein were decreased. After KIRA6 injection into epididymal adipose tissue of rats with periodontitis, adiponectin levels in visceral adipocytes increased, and serum adiponectin levels recovered to a certain extent. The protein expression levels of GRP78 and p-IRE1α/IRE1α were increased and adiponectin protein expression was decreased in P.g-LPS-induced visceral adipocytes. Overexpression of IRE1α further inhibited adiponectin expression in P.g-LPS-stimulated visceral adipocytes, and conversely, IRE1α inhibition restored adiponectin expression. Conclusions Our findings suggest that periodontitis induces ERS in visceral adipocytes leading to hypoadiponectinemia. IRE1α is a key protein regulating adiponectin expression in visceral adipocytes.
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spelling doaj.art-2b79d60af2a04bd9bd924a21d750bac82023-12-24T12:31:05ZengBMCBMC Oral Health1472-68312023-12-0123111210.1186/s12903-023-03758-6Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytesQianqi Wu0Li Yan1Xiao Wu2Yiyan Chen3Leilei Ye4Yingtao Lv5Yuan Su6Stomatology Center, Shunde Hospital, Southern Medical University, The First People’s Hospital of ShundeStomatology Center, Shunde Hospital, Southern Medical University, The First People’s Hospital of ShundeStomatology Center, Shunde Hospital, Southern Medical University, The First People’s Hospital of ShundeStomatology Center, Shunde Hospital, Southern Medical University, The First People’s Hospital of ShundeDepartment of Periodontology, Stomatological Hospital, Southern Medical UniversityDepartment of Implantology and Prosthodontics, Stomatological Hospital, Southern Medical UniversityStomatology Center, Shunde Hospital, Southern Medical University, The First People’s Hospital of ShundeAbstract Backgroud Hypoadiponectinemia is the important cause of insulin resistance. Recent studies have shown that periodontitis is associated with hypoadiponectinemia. The purpose of this study was to investigate the effect of periodontitis-induced endoplasmic reticulum stress (ERS) in visceral adipocytes on hypoadiponectinemia. Methods Rat periodontitis models were established by local ligation with silk around the bilateral maxillary second molars. Porphyromonas gingivalis-lipopolysaccharid (P.g-LPS) was also used to stimulate the visceral adipocytes in vitro. The protein expression levels of glucose regulated protein 78 (GRP78), inositol-requiring protein 1α (IRE1α), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and adiponectin were detected. IRE1α lentiviruses were transfected into visceral adipocytes in vitro, and an IRE1α inhibitor (KIRA6) was injected in epididymal adipose tissue of rats to detect and verify the effect of ERS on adiponectin expression in visceral adipocytes in vivo. Results Hypoadiponectinemia was observed in periodontitis rat, and the expression levels of ERS key proteins GRP78 and the phosphorylation levels of IRE1α (p-IRE1α)/IRE1α in visceral adipocytes were increased, while the expression levels of adiponectin protein were decreased. After KIRA6 injection into epididymal adipose tissue of rats with periodontitis, adiponectin levels in visceral adipocytes increased, and serum adiponectin levels recovered to a certain extent. The protein expression levels of GRP78 and p-IRE1α/IRE1α were increased and adiponectin protein expression was decreased in P.g-LPS-induced visceral adipocytes. Overexpression of IRE1α further inhibited adiponectin expression in P.g-LPS-stimulated visceral adipocytes, and conversely, IRE1α inhibition restored adiponectin expression. Conclusions Our findings suggest that periodontitis induces ERS in visceral adipocytes leading to hypoadiponectinemia. IRE1α is a key protein regulating adiponectin expression in visceral adipocytes.https://doi.org/10.1186/s12903-023-03758-6PeriodontitisEndoplasmic reticulum stressHypoadiponectinemiaGRP78IRE1α
spellingShingle Qianqi Wu
Li Yan
Xiao Wu
Yiyan Chen
Leilei Ye
Yingtao Lv
Yuan Su
Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes
BMC Oral Health
Periodontitis
Endoplasmic reticulum stress
Hypoadiponectinemia
GRP78
IRE1α
title Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes
title_full Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes
title_fullStr Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes
title_full_unstemmed Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes
title_short Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes
title_sort experimental periodontitis induced hypoadiponectinemia by ire1α mediated endoplasmic reticulum stress in adipocytes
topic Periodontitis
Endoplasmic reticulum stress
Hypoadiponectinemia
GRP78
IRE1α
url https://doi.org/10.1186/s12903-023-03758-6
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