Anti-inflammatory role of Gpnmb in adipose tissue of mice

Abstract Obesity can cause a chronic, low-grade inflammation, which is a critical step in the development of type II diabetes and cardiovascular diseases. Inflammation is associated with the expression of glycoprotein nonmetastatic melanoma protein b (Gpnmb), which is mainly expressed by macrophages...

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Autores principales:	Bernadette Nickl, Fatimunnisa Qadri, Michael Bader
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d101d31bdf574e0aa959f99b294e32ac
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spelling	oai:doaj.org-article:d101d31bdf574e0aa959f99b294e32ac2021-12-02T18:37:08ZAnti-inflammatory role of Gpnmb in adipose tissue of mice10.1038/s41598-021-99090-62045-2322https://doaj.org/article/d101d31bdf574e0aa959f99b294e32ac2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99090-6https://doaj.org/toc/2045-2322Abstract Obesity can cause a chronic, low-grade inflammation, which is a critical step in the development of type II diabetes and cardiovascular diseases. Inflammation is associated with the expression of glycoprotein nonmetastatic melanoma protein b (Gpnmb), which is mainly expressed by macrophages and dendritic cells. We generated a Gpnmb-knockout mouse line using Crispr-Cas9 to assess the role of Gpnmb in a diet-induced obesity. The absence of Gpnmb did not affect body weight gain and blood lipid parameters. While wildtype animals became obese but remained otherwise metabolically healthy, Gpnmb-knockout animals developed, in addition to obesity, symptoms of metabolic syndrome such as adipose tissue inflammation, insulin resistance and liver fibrosis. We observed a strong Gpnmb expression in adipose tissue macrophages in wildtype animals and a decreased expression of most macrophage-related genes independent of their inflammatory function. This was corroborated by in vitro data showing that Gpnmb was mostly expressed by reparative macrophages while only pro-inflammatory stimuli induced shedding of Gpnmb. The data suggest that Gpnmb is ameliorating adipose tissue inflammation independent of the polarization of macrophages. Taken together, the data suggest an immune-balancing function of Gpnmb that could delay the metabolic damage caused by the induction of obesity.Bernadette NicklFatimunnisa QadriMichael BaderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bernadette Nickl Fatimunnisa Qadri Michael Bader Anti-inflammatory role of Gpnmb in adipose tissue of mice
description	Abstract Obesity can cause a chronic, low-grade inflammation, which is a critical step in the development of type II diabetes and cardiovascular diseases. Inflammation is associated with the expression of glycoprotein nonmetastatic melanoma protein b (Gpnmb), which is mainly expressed by macrophages and dendritic cells. We generated a Gpnmb-knockout mouse line using Crispr-Cas9 to assess the role of Gpnmb in a diet-induced obesity. The absence of Gpnmb did not affect body weight gain and blood lipid parameters. While wildtype animals became obese but remained otherwise metabolically healthy, Gpnmb-knockout animals developed, in addition to obesity, symptoms of metabolic syndrome such as adipose tissue inflammation, insulin resistance and liver fibrosis. We observed a strong Gpnmb expression in adipose tissue macrophages in wildtype animals and a decreased expression of most macrophage-related genes independent of their inflammatory function. This was corroborated by in vitro data showing that Gpnmb was mostly expressed by reparative macrophages while only pro-inflammatory stimuli induced shedding of Gpnmb. The data suggest that Gpnmb is ameliorating adipose tissue inflammation independent of the polarization of macrophages. Taken together, the data suggest an immune-balancing function of Gpnmb that could delay the metabolic damage caused by the induction of obesity.
format	article
author	Bernadette Nickl Fatimunnisa Qadri Michael Bader
author_facet	Bernadette Nickl Fatimunnisa Qadri Michael Bader
author_sort	Bernadette Nickl
title	Anti-inflammatory role of Gpnmb in adipose tissue of mice
title_short	Anti-inflammatory role of Gpnmb in adipose tissue of mice
title_full	Anti-inflammatory role of Gpnmb in adipose tissue of mice
title_fullStr	Anti-inflammatory role of Gpnmb in adipose tissue of mice
title_full_unstemmed	Anti-inflammatory role of Gpnmb in adipose tissue of mice
title_sort	anti-inflammatory role of gpnmb in adipose tissue of mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d101d31bdf574e0aa959f99b294e32ac
work_keys_str_mv	AT bernadettenickl antiinflammatoryroleofgpnmbinadiposetissueofmice AT fatimunnisaqadri antiinflammatoryroleofgpnmbinadiposetissueofmice AT michaelbader antiinflammatoryroleofgpnmbinadiposetissueofmice
_version_	1718377827723640832

Anti-inflammatory role of Gpnmb in adipose tissue of mice

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