Weight gain in relation to plasma levels of complement factor 3:: results from a population-based cohort study

Aims/hypothesis: Mice that are deficient for complement factor 3 (C3) have shown resistance to weight gain, despite increased food intake. Cross-sectional studies of humans have reported correlations between C3 and obesity. This longitudinal study explored whether C3 predicts a large weight gain in middle-aged men. Methods: Plasma concentrations of C3 and complement factor 4 (C4) were measured in 2,706 non-diabetic healthy men aged between 38 and 50 years, who were re-examined after a mean period of 6.1 years. Results: After adjustments for initial weight, age, height and follow-up time, the odds of incurring large weight gain (75th percentile, >= 3.8 kg) were 1.00 (reference), 0.96 (95% CI:0.7-1.2), 1.1 (CI:0.9-1.5) and 1.4 (CI:1.1-1.8), respectively, among men with C3 levels in the first, second, third and fourth quartiles (p for trend=0.01) respectively. This relationship remained significant after further adjustments for lifestyle factors (physical inactivity, alcohol, smoking), metabolic factors (glucose or homeostasis model assessment values, cholesterol, triglycerides), inflammatory markers (fibrinogen, haptoglobin, ceruloplasmin, orosomucoid, alpha 1-antitrypsin) and for C4. C4 was associated with weight gain after adjustments for initial weight, height, follow-up time and lifestyle factors, but not after adjustments for C3. Conclusions/interpretation: C3 is a risk factor for incurring large weight gain in middle-aged men.