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.