title: Lipoprotein lipase deficiency is associated with elevated acylation stimulating protein plasma levels.
abstract: Acylation stimulating protein (ASP, C3adesArg) is an adipose tissue derived hormone that stimulates triglyceride (TG) synthesis. ASP stimulates lipoprotein lipase (LPL) activity by relieving feedback inhibition caused by fatty acids (FA). The present study examines plasma ASP and lipids in male and female LPL-deficient subjects primarily with the P207L mutation, common in the population of Quebec, Canada. We evaluated the fasting and postprandial states of LPL heterozygotes and fasting levels in LPL homozygotes. Homozygotes displayed increased ASP (58-175% increase, P < 0.05-0.01), reduced HDL-cholesterol (64-75% decrease, P < 0.0001), and elevated levels of TG (19-38-fold, P < 0.0001) versus control (CTL) subjects. LPL heterozygotes with normal fasting TG (1.3-1.9 mmol/l) displayed increased ASP (101-137% increase, P < 0.05-0.01) and delayed TG clearance after a fatload; glucose levels remained similar to controls. Hypertriglyceridemics with no known LPL mutation also had increased ASP levels (63-192% increase, P < 0.001). High-TG LPL heterozygotes were administered a fatload before and after fibrate treatment. The treatment reduced fasting and postprandial plasma ASP, TG, and FA levels without changing insulin or glucose levels. ASP enhances adipose tissue fatty-acid trapping following a meal; however in LPL deficiency, high ASP levels are coupled with delayed lipid clearance.
authors.affiliation: Biochemistry Department and Faculty of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Sabina
authors.initials: S
authors.lastname: Paglialunga
authors.forename: Pierre
authors.initials: P
authors.lastname: Julien
authors.forename: Youssef
authors.initials: Y
authors.lastname: Tahiri
authors.forename: Francois
authors.initials: F
authors.lastname: Cadelis
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D008076:Cholesterol, HDL / Q000097:blood; D015926:Complement C3a / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D008071:Lipoprotein Lipase