A randomized diet‐induced weight‐loss intervention reduces plasma complement C3: Possible implication for endothelial dysfunction

OBJECTIVE: Complement C3 and other components of the alternative pathway are higher in individuals with obesity. Moreover, C3 has been identified as a risk factor for cardiovascular disease. This study investigated whether, and how, a weight‐loss intervention reduced plasma C3, activated C3 (C3a), and factor D and explored potential biological effects of such a reduction. METHODS: The study measured plasma C3, C3a, and factor D by ELISA and measured visceral adipose tissue, subcutaneous adipose tissue, and intrahepatic lipid by magnetic resonance imaging in lean men (n = 25) and men with abdominal obesity (n = 52). The men with obesity were randomized to habitual diet or an 8‐week dietary weight‐loss intervention. RESULTS: The intervention significantly reduced C3 (−0.15 g/L [95% CI: −0.23 to −0.07]), but not C3a or factor D. The C3 reduction was mainly explained by reduction in visceral adipose tissue but not subcutaneous adipose tissue or intrahepatic lipid. This reduction in C3 explained a part of the weight‐loss‐induced improvement of markers of endothelial dysfunction, particularly the reduction in soluble endothelial selectin and soluble intercellular adhesion molecule. CONCLUSIONS: Diet‐induced weight loss in men with abdominal obesity could be a way to lower plasma C3 and thereby improve endothelial dysfunction. C3 reduction may be part of the mechanism via which diet‐induced weight loss could ameliorate the risk of cardiovascular disease in men with abdominal obesity.