CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype

Abstract Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adi...

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Autores principales:	Jingchang Ma, Wei Hu, Dongliang Zhang, Jiangang Xie, Chujun Duan, Yitian Liu, Yuling Wang, Xuexue Xu, Kun Cheng, Boquan Jin, Yuan Zhang, Ran Zhuang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	CD226 HFD Obesity Macrophage Polarization Medicine R
Acceso en línea:	https://doaj.org/article/8f76a5da7c31451281311ca9e33151a8
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spelling	oai:doaj.org-article:8f76a5da7c31451281311ca9e33151a82021-11-28T12:06:43ZCD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype10.1186/s12967-021-03150-41479-5876https://doaj.org/article/8f76a5da7c31451281311ca9e33151a82021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03150-4https://doaj.org/toc/1479-5876Abstract Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. Using a high-fat diet (HFD)–induced mouse obesity model, we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout (KO) of CD226 alleviated obesity caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity.Jingchang MaWei HuDongliang ZhangJiangang XieChujun DuanYitian LiuYuling WangXuexue XuKun ChengBoquan JinYuan ZhangRan ZhuangBMCarticleCD226HFDObesityMacrophagePolarizationMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD226 HFD Obesity Macrophage Polarization Medicine R
spellingShingle	CD226 HFD Obesity Macrophage Polarization Medicine R Jingchang Ma Wei Hu Dongliang Zhang Jiangang Xie Chujun Duan Yitian Liu Yuling Wang Xuexue Xu Kun Cheng Boquan Jin Yuan Zhang Ran Zhuang CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
description	Abstract Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. Using a high-fat diet (HFD)–induced mouse obesity model, we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout (KO) of CD226 alleviated obesity caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity.
format	article
author	Jingchang Ma Wei Hu Dongliang Zhang Jiangang Xie Chujun Duan Yitian Liu Yuling Wang Xuexue Xu Kun Cheng Boquan Jin Yuan Zhang Ran Zhuang
author_facet	Jingchang Ma Wei Hu Dongliang Zhang Jiangang Xie Chujun Duan Yitian Liu Yuling Wang Xuexue Xu Kun Cheng Boquan Jin Yuan Zhang Ran Zhuang
author_sort	Jingchang Ma
title	CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
title_short	CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
title_full	CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
title_fullStr	CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
title_full_unstemmed	CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
title_sort	cd226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8f76a5da7c31451281311ca9e33151a8
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_version_	1718408212116406272

CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype

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