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Longitudinal associations of the alternative and terminal pathways of complement activation with adiposity: The CODAM
Ying Xin1, Elisabeth Hertle1, Carla J H van der Kallen1
1Dept. of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands.
Insights
The alternative complement pathway, especially C3 and factor H (FH), is linked to increased body mass index (BMI) over time. These findings suggest a role for complement activation in adiposity development.
Area of Science:
- Immunology
- Metabolic Health
- Human Physiology
Background:
- The complement system is a crucial part of innate immunity.
- Dysregulation of the complement system has been implicated in various chronic diseases.
- The specific role of complement pathways in the development of adiposity is not fully understood.
Purpose of the Study:
- To investigate the longitudinal associations between components of the alternative and terminal complement pathways and adiposity.
- To determine if changes in complement component levels correlate with changes in body mass index (BMI).
Main Methods:
- Prospective human cohort study with 574 participants at baseline and 489 after 7 years.
- Generalized estimating equations used to assess longitudinal associations between complement components and BMI.
- Multiple linear regression models used to analyze associations between changes in complement levels and BMI, adjusted for covariates.
Main Results:
- Baseline C3, C3a, factor D (FD), factor H (FH), and properdin were positively associated with BMI over 7 years.
- No significant associations were found for Bb, C5a, or sC5b-9.
- Increases in C3 and FH levels were significantly associated with increases in BMI over the study period.
Conclusions:
- Activation of the alternative complement pathway may play a role in the development of adiposity.
- Further research is needed to establish a causal link between specific alternative pathway components and human obesity.
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.
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