Regulation of alternative pathway activation and C3a production by adipose cells.
Adipose tissue is a major source of adpisin/factor D of the alternative pathway of complement. Adipose tissue also expresses the two other complement components which are involved in the first activation step of the alternative pathway, factor B and C3, and this step is activated in adipose tissue, producing C3a/Acylation Stimulating Protein (C3a/ASP), a stimulator of triglyceride synthesis. Complement activation is a highly regulated process, however, nothing is known about regulation of complement activation in adipose tissue. To gain insight into the nature of adipose complement activation and its regulation, we have now examined the expression of several complement activation regulatory genes, and analyzed the production of C3a/ASP in lean vs. obese, adpisin-deficient mice. We found that undifferentiated preadipocytes expressed the mRNAs encoding the negative regulatory proteins Crry and factor H, but expression of both genes was decreased upon differentiation. The positive regulator properdin, as well as Crry and factor H, were found in adipose tissue. None of these genes was regulated in murine genetic obesity. To investigate the relative levels of complement activation in lean vs. adpisin-deficient obese mice, we developed a radioimmunoassay for measurement of murine C3a/ASP in plasma. We report that there was no significant difference in the level of C3a in lean vs. obese plasma; however, we found a positive correlation between C3a and plasma triglyceride levels in normal lean mice.
Choy
L N
LN
Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Spiegelman
B M
BM
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001055:Apolipoproteins B / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D015152:Blotting, Northern; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a / Q000031:analogs & derivatives*; D011415:Complement Factor B / Q000378:metabolism; D011416:Complement Factor D / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D015342:DNA Probes; D005786:Gene Expression Regulation; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000097:blood*; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001798:Blood Proteins; D003176:Complement C3; D015342:DNA Probes; D011994:Recombinant Proteins; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D003165:Complement System Proteins; D012697:Serine Endopeptidases; D011416:Complement Factor D; C493491:complement factor D, mouse; D011415:Complement Factor B