title: Obesity-inducing diet promotes acylation stimulating protein resistance.
abstract: Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system that is involved in energy homeostasis and inflammation. ASP acts on and correlates positively with postprandial fat clearance in healthy subjects. However, in obesity, ASP levels are elevated and correlate inversely with fat clearance, indicative of a potential resistance to ASP. Using a mouse model, we hypothesized that, over time, diet-induced obesity (DIO) would result in development of ASP insensitivity, as compared to chow-fed animals as controls. Injection of recombinant ASP in DIO mice failed to accelerate fat clearance to the same extent as in chow-fed mice. DIO mice exhibited higher basal levels of plasma ASP and, after 30weeks of diet, showed lower ASP receptor (C5L2) expression in adipose tissue compared to chow-fed mice. Additionally, ex vivo ASP stimulation failed to induce normal Ser(473)AKT phosphorylation in adipose tissue from DIO mice VS chow-fed controls. These results demonstrate for the first time a state of diet-induced ASP resistance. Changes in the ASP-C5L2 pathway dynamics in obesity could alter the development of obesity and co-morbidities such as atherosclerosis and type 2 diabetes.
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fisette
authors.forename: Marc
authors.initials: M
authors.lastname: Lapointe
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000821:Animal Feed; D000818:Animals; D015926:Complement C3a / Q000008:administration & dosage* / Q000378:metabolism* / Q000502:physiology; D015936:Complement C5a / Q000096:biosynthesis; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D011897:Random Allocation; D012680:Sensitivity and Specificity
chemical_list: D004041:Dietary Fats; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D015936:Complement C5a
keywords: ASP; AUC; Acylation stimulating protein; Adipokine; GAPDH; HF/HS; LF; Lipid metabolism; Obesity; Resistance; TG; acylation stimulating protein; area under the curve; glyceraldehyde 3-phosphate dehydrogenase; high-fat high-sucrose; low-fat; triglyceride