Adipsin and an endogenous pathway of complement from adipose cells.
The alternative complement pathway is best known for its role in humoral suppression of infectious agents. We have previously shown that adipose cells synthesize adipsin, the mouse homolog of human complement factor D, and that the synthesis of this protein is reduced in several rodent models of obesity. We show here that adipose cells and adipose tissue also synthesize two other essential components of the alternative pathway of complement, factors C3 and B, and activate the proximal portion of this pathway. This activation occurs in the absence of infectious agents and without triggering the terminal, lytic part of this pathway. We demonstrate the production in vitro of several polypeptides characteristic of complement activation that are known to have potent biological activities, including the anaphylatoxin C3a. Cultured adipocytes require stimulation with cytokines to activate complement, while explanted adipose tissue has no such requirement. The adipose tissue from obese mice is deficient in this localized activation of the alternative pathway. These results indicate that complement activation occurs in a localized site, adipose tissue, in normal mice and is impaired in a state of metabolic dysfunction. This suggests a novel function for the proximal portion of this complement pathway related to adipose cell biology or energy balance.
Choy
L N
LN
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Rosen
B S
BS
Spiegelman
B M
BM
D016475:3T3 Cells; D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D015152:Blotting, Northern; D011416:Complement Factor D; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*
D012333:RNA, Messenger; D003165:Complement System Proteins; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; C493491:complement factor D, mouse