title: Paradoxical glucose-sensitizing yet proinflammatory effects of acute ASP administration in mice.
abstract: 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.
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Y4332, 2725 Chemin Ste-Foy, Québec, QC, Canada G1V 4G5.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fisette
authors.forename: Pegah
authors.initials: P
authors.lastname: Poursharifi
authors.forename: Katerina
authors.initials: K
authors.lastname: Oikonomopoulou
authors.forename: Mercedes N
authors.initials: MN
authors.lastname: Munkonda
authors.forename: Marc
authors.initials: M
authors.lastname: Lapointe
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D015926:Complement C3a / Q000494:pharmacology*; D004041:Dietary Fats / Q000009:adverse effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004041:Dietary Fats; D007328:Insulin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a