Longitudinal associations of the alternative and terminal pathways of complement activation with adiposity: The CODAM study

Objective: To investigate longitudinal associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], and properdin) and the terminal complement pathway (C5a, sC5b-9) with adiposity. Methods: A prospective human cohort study (n = 574 at baseline, n = 489 after 7 years follow-up) was analyzed. Generalized estimating equations were used to evaluate the longitudinal associations between complement components (standardized values) and adiposity (main outcome BMI [kg/m(2)]). Multiple linear regression models were used to investigate the associations between change in complement levels and change in BMI. Analyses were adjusted for age, sex, medication and lifestyle. Results: Over the 7-year period, baseline C3 was positively associated with BMI (beta = 1.72 [95% confidence interval (CI): 1.35; 2.09]). Positive associations were also observed for C3a (beta = 0.64 [0.31; 0.97]), FD (beta = 1.00 [0.59; 1.42]), FH (beta = 1.17 [0.82; 1.53 ]), and properdin (beta = 0.60 [0.28; 0.92]), but not for Bb, C5a or sC5b-9. Moreover, changes in C3 ((3= 0.52 [0.34; 0.71 ]) and FH (beta = 0.51 [0.32; 0.70]) were significantly associated with changes in BMI. Conclusions: The complement system, particularly activation of the alternative pathway, may be involved in development of adiposity. Whether individual aspects of alternative pathway activation have a causal role in human obesity, remains to be investigated. (C) 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.