Ying Xin1, Elisabeth Hertle1, Carla J H van der Kallen1, Casper G Schalkwijk1, Coen D A Stehouwer1, Marleen M J van Greevenbroek2. 1. Dept. of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands. 2. Dept. of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands. Electronic address: m.vangreevenbroek@maastrichtuniversity.nl.
Abstract
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/m2]). 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 (β=1.72 [95% confidence interval (CI): 1.35; 2.09]). Positive associations were also observed for C3a (β=0.64 [0.31; 0.97]), FD (β=1.00 [0.59; 1.42]), FH (β=1.17 [0.82; 1.53]), and properdin (β=0.60 [0.28; 0.92]), but not for Bb, C5a or sC5b-9. Moreover, changes in C3 (β=0.52 [0.34; 0.71]) and FH (β=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.
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/m2]). 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 (β=1.72 [95% confidence interval (CI): 1.35; 2.09]). Positive associations were also observed for C3a (β=0.64 [0.31; 0.97]), FD (β=1.00 [0.59; 1.42]), FH (β=1.17 [0.82; 1.53]), and properdin (β=0.60 [0.28; 0.92]), but not for Bb, C5a or sC5b-9. Moreover, changes in C3 (β=0.52 [0.34; 0.71]) and FH (β=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 humanobesity, remains to be investigated.
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