Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.

<h4>Background</h4>Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT) of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function,...

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Autores principales:	Danny Gauvreau, Abhishek Gupta, Alexandre Fisette, Fun-Qun Tom, Katherine Cianflone
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/816eb70e418949ebbc193c112ba23700
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spelling	oai:doaj.org-article:816eb70e418949ebbc193c112ba237002021-11-18T07:48:36ZDeficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.1932-620310.1371/journal.pone.0060795https://doaj.org/article/816eb70e418949ebbc193c112ba237002013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23630572/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT) of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP), and C5a, involved in innate immunity.<h4>Aim</h4>We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl) and C5L2 knock-out (C5L2(-/-)) mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO) conditions.<h4>Results</h4>In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold) both over time and with DIO. By contrast, in C5L2(-/-), there was no change in C5aR in WAT. C5L2(-/-) mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro-) vs M2 (anti-inflammatory) macrophage proportion was unchanged but C5L2(-/-) adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2(-/-) mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2(-/-) mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance.<h4>Conclusion</h4>Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.Danny GauvreauAbhishek GuptaAlexandre FisetteFun-Qun TomKatherine CianflonePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60795 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Danny Gauvreau Abhishek Gupta Alexandre Fisette Fun-Qun Tom Katherine Cianflone Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.
description	<h4>Background</h4>Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT) of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP), and C5a, involved in innate immunity.<h4>Aim</h4>We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl) and C5L2 knock-out (C5L2(-/-)) mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO) conditions.<h4>Results</h4>In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold) both over time and with DIO. By contrast, in C5L2(-/-), there was no change in C5aR in WAT. C5L2(-/-) mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro-) vs M2 (anti-inflammatory) macrophage proportion was unchanged but C5L2(-/-) adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2(-/-) mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2(-/-) mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance.<h4>Conclusion</h4>Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.
format	article
author	Danny Gauvreau Abhishek Gupta Alexandre Fisette Fun-Qun Tom Katherine Cianflone
author_facet	Danny Gauvreau Abhishek Gupta Alexandre Fisette Fun-Qun Tom Katherine Cianflone
author_sort	Danny Gauvreau
title	Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.
title_short	Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.
title_full	Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.
title_fullStr	Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.
title_full_unstemmed	Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.
title_sort	deficiency of c5l2 increases macrophage infiltration and alters adipose tissue function in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/816eb70e418949ebbc193c112ba23700
work_keys_str_mv	AT dannygauvreau deficiencyofc5l2increasesmacrophageinfiltrationandaltersadiposetissuefunctioninmice AT abhishekgupta deficiencyofc5l2increasesmacrophageinfiltrationandaltersadiposetissuefunctioninmice AT alexandrefisette deficiencyofc5l2increasesmacrophageinfiltrationandaltersadiposetissuefunctioninmice AT funquntom deficiencyofc5l2increasesmacrophageinfiltrationandaltersadiposetissuefunctioninmice AT katherinecianflone deficiencyofc5l2increasesmacrophageinfiltrationandaltersadiposetissuefunctioninmice
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Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.

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