Mice lacking acylation stimulating protein (ASP) have delayed postprandial triglyceride clearance.
Acylation stimulating protein (ASP) is a 76 amino acid fragment of the third component of complement (C3) which is generated by the interaction of adipsin and factor B with C3. In vitro studies have shown that ASP can markedly increase triglyceride synthesis in adipocytes. To test the ASP pathway in vivo, C3-deficient mice, and therefore ASP-deficient mice, were generated and oral fat loads were conducted in wild-type (C3+/+) and mutant (C3-/-) animals. The principal results were: 1) postprandial triglyceride clearance was significantly delayed in mutant compared to wild-type mice; 2) this difference was more pronounced in males compared to females; 3) in both males and females, the differences were more pronounced in the second half of the postprandial period; 4) fasting and postprandial free fatty acid (FFA) were higher in C3(-/-) than in C3(+/+) males; and 5) intraperitoneal administration of ASP accelerated triglyceride clearance in C3(-/-) males. The data are consistent therefore, with the hypothesis that the ASP pathway is an important physiologic determinant of normal postprandial triglyceride clearance.
Murray
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Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal, Quebec, Canada H3A 1A1.
Sniderman
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Cianflone
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D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015926:Complement C3a / Q000031:analogs & derivatives*; D017931:DNA Primers / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012727:Sex Characteristics; D014280:Triglycerides / Q000097:blood*
D001798:Blood Proteins; D003176:Complement C3; D017931:DNA Primers; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a