title: Adipsin/acylation stimulating protein system in human adipocytes: regulation of triacylglycerol synthesis.
abstract: Through their capacity to store fatty acids as triacylglycerol molecules, adipocytes serve a vital physiologic role. This study presents further evidence that this process can be modulated in human adipocytes by the adipsin/acylation stimulating protein (ASP) pathway and suggests a novel function for the product of this system--ASP. The data demonstrate the following: (1) ASP stimulates triacylglycerol synthesis within adipocytes, and this occurs to a greater extent in differentiating than undifferentiated cells (242% +/- 32% vs 168% +/- 11%, p < 0.01, respectively, at an ASP concentration of 88 ng/mL; (2) ASP does not affect the Km for triacylglycerol synthesis but does substantially increase Vmax; (3) when ASP is generated in vitro through incubation of its precursor proteins under appropriate conditions, triacylglycerol synthesis increases to the same extent as when plasma-purified ASP is added to the medium; (4) human adipocytes contain mRNA for the specific serine protease adipsin and the two precursor proteins C3 and factor B required to interact for the production of ASP; and (5) the extent to which cultured differentiating adipocytes produce ASP is proportional to the degree to which they have accumulated triacylglycerol mass during differentiation (r2 = 0.7523, p < 0.0005). These findings provide the first evidence for the existence of the adipsin/ASP pathway in human adipocytes, and this may markedly enhance our understanding of the processes which regulate triacylglycerol clearance from plasma.
authors.affiliation: McGill Unit for the Prevention of Cardiovascular Disease, Royal Victoria Hospital, Montreal, Quebec, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Cianflone
authors.forename: D A
authors.initials: DA
authors.lastname: Roncari
authors.forename: M
authors.initials: M
authors.lastname: Maslowska
authors.forename: A
authors.initials: A
authors.lastname: Baldo
authors.forename: J
authors.initials: J
authors.lastname: Forden
authors.forename: A D
authors.initials: AD
authors.lastname: Sniderman
mesh_terms: D000215:Acylation; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D015926:Complement C3a / Q000235:genetics / Q000378:metabolism; D011415:Complement Factor B / Q000235:genetics / Q000378:metabolism; D011416:Complement Factor D; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D001798:Blood Proteins; D003176:Complement C3; D012333:RNA, Messenger; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; D011415:Complement Factor B