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.
Highlights
The past decades of obesity research have seen a change of paradigm
Adipose tissue was once labeled as a passive storage organ, while obesity comorbidities were predominantly linked with energy metabolism disorders
The aim of the present study was to assess the effects of acute Acylation stimulating protein (ASP) administration on in vivo glucose metabolism and rapid inflammatory responses in a diet-induced obesity (DIO) mouse model
Summary
The past decades of obesity research have seen a change of paradigm. Adipose tissue was once labeled as a passive storage organ, while obesity comorbidities were predominantly linked with energy metabolism disorders. It is widely recognized that adipose tissue plays a major endocrine role and that progressive metabolic diseases such as type 2 diabetes and atherosclerosis manifest a strong immune component. Acylation stimulating protein (ASP), identical to C3adesArg, is a protein generated through the alternative complement pathway of the immune system [2]. C3a/C3adesArg is rapidly produced during acute immunological responses such as bacterial infection, which triggers the classical or lectin pathways of the complement system. ASP acts through its only known receptor, C5L2 This 7-transmembrane receptor is widely expressed, with expression in tissues such as liver, muscle, adipose tissue, immune cells, and brain, and C5L2 shares significant homology with other complement receptors such as C3a receptor and C5a receptor [3]
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