Role of Complement and Complement-Related Adipokines in Regulation of Energy Metabolism and Fat Storage

Adipose tissue releases many cytokines and inflammatory factors described as adipokines. In obesity, adipokines released from expanding adipose tissue are implicated in disease progression and metabolic dysfunction. However, mechanisms controlling the progression of adiposity and metabolic complications are not fully understood. It has been suggested that expanding fat mass and sustained release of inflammatory adipokines in adipose tissue lead to hypoxia, oxidative stress, apoptosis, and cellular damage. These changes trigger an immune response involving infiltration of adipose tissue with immune cells, complement activation and generation of factors involved in opsonization and clearance of damaged cells. Abundant evidence now indicates that adipose tissue is an active secretory source of complement and complement-related adipokines that, in addition to their inflammatory role, contribute to the regulation of metabolic function. This article highlights advances in knowledge regarding the role of these adipokines in energy regulation of adipose tissue through modulating lipogenic and lipolytic pathways. Several adipokines will be discussed including adipsin, Factor H, properdin, C3a, Acylation-Stimulating Protein, C1q/TNF-related proteins, and response gene to complement-32 (RGC-32). Interactions between these factors will be described considering their immune-metabolic roles in the adipose tissue microenvironment and their potential contribution to progression of adiposity and metabolic dysfunction. The differential expression and the role of complement factors in gender-related fat partitioning will also be addressed. Identifying lipogenic adipokines and their specific autocrine/paracrine roles may provide means for adipose-tissue-targeted therapeutic interventions that may disrupt the vicious circle of adiposity and disease progression. © 2019 American Physiological Society. Compr Physiol 9:1411-1429, 2019.