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

Abstract

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, α1-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 middleaged men.

Complement Factor 3 Is Associated With Insulin Resistance and With Incident Type 2 Diabetes Over a 7-Year Follow-up Period: The CODAM Study

“…Adjustments for an ascending proxy are not always prudent, as they can attenuate estimates due to differences in bias and variance between waist circumference and C3 (44). Moreover, it has been suggested that C3 may actually cause obesity (45), in which case changes in obesity should be considered a mediator for which adjustment is not wanted (Supplementary Fig. 1C).…”

Selenium intake reduces serum C3, an early marker of metabolic syndrome manifestations, in healthy young adults

“…As C3 is associated with smoking status (Engstrom et al, 2005a), risk factors of obesity (Engstrom et al, 2005a), type 2 diabetes (Engstrom et al, 2005b), cardiovascular diseases (Onat et al, 2005) and several complications associated with inflammation (Kriketos et al, 2004) and inflammatory biomarkers (Halkes et al, 2001;Sampietro et al, 2004), C3 should be a good candidate as a marker of inflammation. However, we could not directly correlate smoking status neither physical activity with C3 concentrations although an effect of those variables was evident in our trial.…”

“…Thus, an increase in C3 concentrations is associated, among other mediators, with cardiovascular disease features (Muscari et al, 2005), insulin resistance, body weight gain (Engstrom et al, 2005a), waist circumference and both high fasting and postpandrial triacylglycerol concentrations (Halkes et al, 2001). These findings suggest that circulating C3 could be a risk factor on the development of obesity (Engstrom et al, 2005a) and type 2 diabetes (Engstrom et al, 2005b), and a coronary disease risk indicator (Onat et al, 2005). Moreover, C3 concentrations have been shown to be a useful biomarker to identify subjects with metabolic syndrome features (van Oostrom et al, 2007).…”

Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study

“…C3 is associated with overweight and obesity, [16][17][18][19][20]32,33 which is one of the most important risk factors for hypertension. A recent study of risk factor treatment reported that weight loss reduced the C3 levels.…”