Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice

Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system, which stimulates fat storage and is typically increased in obesity, type 2 diabetes, and cardiovascular disease. Using a diet-induced obesity (DIO) mouse model, the acute effects of ASP on energy metabolis...

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Main Authors: Alexandre Fisette, Pegah Poursharifi, Katerina Oikonomopoulou, Mercedes N. Munkonda, Marc Lapointe, Katherine Cianflone
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/713284
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author Alexandre Fisette
Pegah Poursharifi
Katerina Oikonomopoulou
Mercedes N. Munkonda
Marc Lapointe
Katherine Cianflone
author_facet Alexandre Fisette
Pegah Poursharifi
Katerina Oikonomopoulou
Mercedes N. Munkonda
Marc Lapointe
Katherine Cianflone
author_sort Alexandre Fisette
collection DOAJ
description Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system, which stimulates fat storage and is typically increased in obesity, type 2 diabetes, and cardiovascular disease. Using a diet-induced obesity (DIO) mouse model, the acute effects of ASP on energy metabolism and inflammatory processes in vivo were evaluated. We hypothesized that ASP would specifically exert proinflammatory effects. C57Bl/6 wild-type mice were put on a high-fat-high-sucrose diet for 12 weeks. Mice were then subjected to both glucose and insulin tolerance tests, each manipulation being preceded by recombinant ASP or vehicle (control) bolus injection. ASP supplementation increased whole-body glucose excursion, and this was accomplished with reduced concomitant insulin levels. However, ASP did not directly alter insulin sensitivity. ASP supplementation induced a proinflammatory phenotype, with higher levels of cytokines including IL-6 and TNF-α in plasma and in adipose tissue, liver, and skeletal muscle mRNA. Additionally, ASP increased M1 macrophage content of these tissues. ASP exerted a direct concentration-dependent role in the migration and M1 activation of cultured macrophages. Altogether, the in vivo and in vitro experiments demonstrate that ASP plays a role in both energy metabolism and inflammation, with paradoxical whole-body glucose-sensitizing yet proinflammatory effects.
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spelling doaj-art-194d7eec7dae4a69aa5bcf49b76f5b4b2025-02-03T01:33:05ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/713284713284Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in MiceAlexandre Fisette0Pegah Poursharifi1Katerina Oikonomopoulou2Mercedes N. Munkonda3Marc Lapointe4Katherine Cianflone5Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Y4332, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Y4332, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, CanadaDepartment of Pathology & Laboratory Medicine, School of Medicine, University of Pennsylvania, PA 19104-6100, USACentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Y4332, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Y4332, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Y4332, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, CanadaAcylation stimulating protein (ASP) is an adipokine derived from the immune complement system, which stimulates fat storage and is typically increased in obesity, type 2 diabetes, and cardiovascular disease. Using a diet-induced obesity (DIO) mouse model, the acute effects of ASP on energy metabolism and inflammatory processes in vivo were evaluated. We hypothesized that ASP would specifically exert proinflammatory effects. C57Bl/6 wild-type mice were put on a high-fat-high-sucrose diet for 12 weeks. Mice were then subjected to both glucose and insulin tolerance tests, each manipulation being preceded by recombinant ASP or vehicle (control) bolus injection. ASP supplementation increased whole-body glucose excursion, and this was accomplished with reduced concomitant insulin levels. However, ASP did not directly alter insulin sensitivity. ASP supplementation induced a proinflammatory phenotype, with higher levels of cytokines including IL-6 and TNF-α in plasma and in adipose tissue, liver, and skeletal muscle mRNA. Additionally, ASP increased M1 macrophage content of these tissues. ASP exerted a direct concentration-dependent role in the migration and M1 activation of cultured macrophages. Altogether, the in vivo and in vitro experiments demonstrate that ASP plays a role in both energy metabolism and inflammation, with paradoxical whole-body glucose-sensitizing yet proinflammatory effects.http://dx.doi.org/10.1155/2013/713284
spellingShingle Alexandre Fisette
Pegah Poursharifi
Katerina Oikonomopoulou
Mercedes N. Munkonda
Marc Lapointe
Katherine Cianflone
Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice
Mediators of Inflammation
title Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice
title_full Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice
title_fullStr Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice
title_full_unstemmed Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice
title_short Paradoxical Glucose-Sensitizing yet Proinflammatory Effects of Acute ASP Administration in Mice
title_sort paradoxical glucose sensitizing yet proinflammatory effects of acute asp administration in mice
url http://dx.doi.org/10.1155/2013/713284
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