Introduction: Increased systemic inflammation plays a significant role in the development
of adult cardiometabolic diseases such as insulin resistance, dyslipidemia, atherosclerosis, and
hypertension. The complement system is a part of the innate immune system and plays a key role in the
regulation of inflammation. Of particular importance is the activation of complement components C3
and C4. C3 is produced primarily by the liver but is also produced in adipocytes, macrophages and
endothelial cells, all of which are present in adipose tissues. Dietary fat and chylomicrons stimulate C3
production. Adipocytes in addition to producing C3 also have receptors for activated C3 and other
complement components and thus also respond to as well as produce a target for complement. C3adesArg,
also known as acylation stimulation factor, increases adipocyte triglyceride synthesis and
release. These physiological effects play a significant role in the development of metabolic syndrome.
Epidemiologically, obese adults and non-obese adults with cardiometabolic disease who are not obese
have been shown to have increased complement levels. C4 levels also correlate with body mass index.
Genetically, specific C3 polymorphisms have been shown to predict future cardiovascular events and.
D decreased C4 long gene copy number is associated with increased longevity.
Conclusion: Future research is clearly needed to clarify the role of complement in the development of
cardiovascular disease and mechanisms for its action. The complement system may provide a new area
for intervention in the prevention of cardiometabolic diseases.