CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.

<h4>Background</h4>Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L defici...

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Autores principales:	Dennis Wolf, Felix Jehle, Alexandra Ortiz Rodriguez, Bianca Dufner, Natalie Hoppe, Christian Colberg, Andrey Lozhkin, Nicole Bassler, Benjamin Rupprecht, Ansgar Wiedemann, Ingo Hilgendorf, Peter Stachon, Florian Willecke, Mark Febbraio, Constantin von zur Muhlen, Christoph J Binder, Christoph Bode, Andreas Zirlik, Karlheinz Peter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7d4422239554d5396a325a3d1078fdd
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spelling	oai:doaj.org-article:f7d4422239554d5396a325a3d1078fdd2021-11-18T07:25:44ZCD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.1932-620310.1371/journal.pone.0033026https://doaj.org/article/f7d4422239554d5396a325a3d1078fdd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412980/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo.<h4>Methodology/principal findings</h4>WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels.<h4>Conclusion</h4>We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.Dennis WolfFelix JehleAlexandra Ortiz RodriguezBianca DufnerNatalie HoppeChristian ColbergAndrey LozhkinNicole BasslerBenjamin RupprechtAnsgar WiedemannIngo HilgendorfPeter StachonFlorian WilleckeMark FebbraioConstantin von zur MuhlenChristoph J BinderChristoph BodeAndreas ZirlikKarlheinz PeterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33026 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dennis Wolf Felix Jehle Alexandra Ortiz Rodriguez Bianca Dufner Natalie Hoppe Christian Colberg Andrey Lozhkin Nicole Bassler Benjamin Rupprecht Ansgar Wiedemann Ingo Hilgendorf Peter Stachon Florian Willecke Mark Febbraio Constantin von zur Muhlen Christoph J Binder Christoph Bode Andreas Zirlik Karlheinz Peter CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
description	<h4>Background</h4>Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo.<h4>Methodology/principal findings</h4>WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels.<h4>Conclusion</h4>We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.
format	article
author	Dennis Wolf Felix Jehle Alexandra Ortiz Rodriguez Bianca Dufner Natalie Hoppe Christian Colberg Andrey Lozhkin Nicole Bassler Benjamin Rupprecht Ansgar Wiedemann Ingo Hilgendorf Peter Stachon Florian Willecke Mark Febbraio Constantin von zur Muhlen Christoph J Binder Christoph Bode Andreas Zirlik Karlheinz Peter
author_facet	Dennis Wolf Felix Jehle Alexandra Ortiz Rodriguez Bianca Dufner Natalie Hoppe Christian Colberg Andrey Lozhkin Nicole Bassler Benjamin Rupprecht Ansgar Wiedemann Ingo Hilgendorf Peter Stachon Florian Willecke Mark Febbraio Constantin von zur Muhlen Christoph J Binder Christoph Bode Andreas Zirlik Karlheinz Peter
author_sort	Dennis Wolf
title	CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
title_short	CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
title_full	CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
title_fullStr	CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
title_full_unstemmed	CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
title_sort	cd40l deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic igg-antibodies.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f7d4422239554d5396a325a3d1078fdd
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CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.

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