Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome

Abstract Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment...

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Main Authors: Yulin Zhang, Ziwei Cheng, Liyu Hong, Jia Liu, Xinyue Ma, Wenjing Wang, Ran Pan, Wenjie Lu, Qichao Luo, Shan Gao, Qin Kong
Format: Article
Language:English
Published: Springer 2023-12-01
Series:Molecular Biomedicine
Subjects:
Online Access:https://doi.org/10.1186/s43556-023-00158-8
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author Yulin Zhang
Ziwei Cheng
Liyu Hong
Jia Liu
Xinyue Ma
Wenjing Wang
Ran Pan
Wenjie Lu
Qichao Luo
Shan Gao
Qin Kong
author_facet Yulin Zhang
Ziwei Cheng
Liyu Hong
Jia Liu
Xinyue Ma
Wenjing Wang
Ran Pan
Wenjie Lu
Qichao Luo
Shan Gao
Qin Kong
author_sort Yulin Zhang
collection DOAJ
description Abstract Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1β production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.
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spelling doaj.art-8d50385a51044303ae61f399a1cd42ed2023-12-10T12:04:32ZengSpringerMolecular Biomedicine2662-86512023-12-014111410.1186/s43556-023-00158-8Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasomeYulin Zhang0Ziwei Cheng1Liyu Hong2Jia Liu3Xinyue Ma4Wenjing Wang5Ran Pan6Wenjie Lu7Qichao Luo8Shan Gao9Qin Kong10Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityThe Second Clinical Medical College, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityRainbowFish Rehabilitation and Nursing School, Hangzhou Vocational and Technical CollegeDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Anhui Medical UniversityAbstract Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1β production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.https://doi.org/10.1186/s43556-023-00158-8Apolipoprotein E (ApoE)Adipose tissueMetabolic inflammationMacrophageNOD-, LRR- and Pyrin Domain-Containing Protein 3 (NLRP3)
spellingShingle Yulin Zhang
Ziwei Cheng
Liyu Hong
Jia Liu
Xinyue Ma
Wenjing Wang
Ran Pan
Wenjie Lu
Qichao Luo
Shan Gao
Qin Kong
Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
Molecular Biomedicine
Apolipoprotein E (ApoE)
Adipose tissue
Metabolic inflammation
Macrophage
NOD-, LRR- and Pyrin Domain-Containing Protein 3 (NLRP3)
title Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
title_full Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
title_fullStr Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
title_full_unstemmed Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
title_short Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
title_sort apolipoprotein e apoe orchestrates adipose tissue inflammation and metabolic disorders through nlrp3 inflammasome
topic Apolipoprotein E (ApoE)
Adipose tissue
Metabolic inflammation
Macrophage
NOD-, LRR- and Pyrin Domain-Containing Protein 3 (NLRP3)
url https://doi.org/10.1186/s43556-023-00158-8
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