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Downregulation of complement C3 and C3aR expression in subcutaneous adipose tissue in obese women
Abhishek Gupta1, Reza Rezvani2, Marc Lapointe2
1Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada; Department of Physiology, King George's Medical University, Lucknow, Uttar Pradesh, India.
Insights
Complement C3 and its receptor C3aR gene expression in subcutaneous adipose tissue decrease with obesity. This finding suggests a role for the complement system in obesity-related metabolic dysfunction.
Area of Science:
- Immunometabolism
- Adipose tissue biology
- Complement system research
Background:
- The complement system's central component, C3, is linked to obesity, metabolic syndrome, and cardiovascular disease, but the mechanisms remain unclear.
- Gene expression of C3, its cleavage product C3a/C3adesArg, and receptor C3aR were investigated in women's adipose tissue.
Purpose of the Study:
- To evaluate the gene expression of C3, C3a/C3adesArg, and C3aR in subcutaneous and omental adipose tissue in relation to obesity.
- To explore the correlation between complement component expression and various anthropometric, metabolic, and adipokine parameters.
Main Methods:
- 140 women (aged 21-69, BMI 19.5-79 kg/m2) were assessed for anthropometric and blood parameters.
- Adipose tissue gene expression was analyzed and correlated with clinical data, with subjects grouped by obesity severity.
Main Results:
- Subcutaneous C3 and C3aR gene expression decreased with increasing adiposity, while omental expression remained unchanged.
- Subcutaneous C3 and C3aR expression correlated with metabolic markers like apoB, apoA1, waist circumference, blood pressure, and glucose.
- Plasma C3a/C3adesArg increased, and adiponectin decreased with BMI, both correlating with subcutaneous C3 and C3aR expression.
Conclusions:
- Obesity down-regulates complement C3 and C3aR specifically in subcutaneous adipose tissue.
- These findings support a role for the complement system in immunometabolism, linking it to obesity-related metabolic alterations.
Background:
The central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.
Methods:
Women (n = 140, 21-69 years, BMI 19.5-79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.
Results:
Subjects were separated into groups (n = 34-36) according to obesity: normal/overweight (≤30 kg/m2), obese I (≤45 kg/m2), obese II (≤51 kg/m2), and obese III (≤80 kg/m2). Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05-0.0001). While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05). Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and C3aR expression (p<0.05-0.001) or less).
Conclusions:
The obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.

