Complement in metabolic disease: metaflammation and a two-edged sword

We are currently experiencing an enduring global epidemic of obesity and diabetes. It is now understood that chronic low-grade tissue inflammation plays an important role in metabolic disease, brought upon by increased uptake of a so-called Western diet, and a more sedentary lifestyle. Many evolutionarily conserved links exist between metabolism and the immune system, and an imbalance in this system induced by chronic over-nutrition has been termed ‘metaflammation’. The complement system is an important and evolutionarily ancient part of innate immunity, but recent work has revealed that complement not only is involved in the recognition of pathogens and induction of inflammation, but also plays important roles in cellular and tissue homeostasis. Complement can therefore contribute both positively and negatively to metabolic control, depending on the nature and anatomical site of its activity. This review will therefore focus on the interactions of complement with mechanisms and tissues relevant for metabolic control, obesity and diabetes.