Regulation of the terminal complement cascade in adipose tissue for control of its volume, cellularity, and fibrosis.

White adipose tissue (WAT) is a reservoir for various pathogens and their products, such as lipopolysaccharides. Therefore, it must be equipped with a defense mechanism connected with the activation of innate immunity. This explains the phenomenon that adipocytes express components of the classical and alternative complement pathways, which can be activated even in the absence of opportunistic pathogens. Terminal stages of the complement pathway are related to the production of membrane attack complexes and, thus, can cause lysis of pathogens, as well as autolysis of host adipocytes, contributing to the regulation of the cellularity in WAT. Complement-induced autolysis of adipocytes is counteracted by a number of cellular defense mechanisms. This versatility of activation and suppression processes enables a broad range of adaptability to physiological contexts, ranging from the development of hypertrophic WAT to lipodystrophy. Pathogen-induced activation of the complement pathway in WAT also induces a profibrotic phenotype. These processes may also be involved in the regulation of insulin resistance in adipocytes. This explains the dual immune/metabolic role of the complement pathway in WAT: the pathway is an integral part of the immune response but also potently involved in the control of volume and cellularity of WAT under both physiological and pathological conditions.