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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Format: | Article |
Language: | English |
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Wiley
2013-01-01
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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. |
format | Article |
id | doaj-art-194d7eec7dae4a69aa5bcf49b76f5b4b |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2013-01-01 |
publisher | Wiley |
record_format | Article |
series | Mediators of Inflammation |
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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