Abstract

BackgroundThe 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.MethodsWomen (n = 140, 21–69 years, BMI 19.5–79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.ResultsSubjects 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).ConclusionsThe 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.

Highlights

  • Obesity and metabolic dysfunction are associated with a state of chronic low-grade inflammation and the importance of that association is still emerging [1]

  • In the present study we evaluated gene expression of complement C3 and C3a receptor (C3aR) in omental and subcutaneous adipose tissue and plasma C3a/ C3adesArg levels in Caucasian women, and their association with anthropometric and biochemical variables over a wide range of degrees of obesity

  • The ratio of SC relative to OM adipose tissue expression was much greater for C3aR than C3 (Figure 1A)

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Summary

Introduction

Obesity and metabolic dysfunction are associated with a state of chronic low-grade inflammation and the importance of that association is still emerging [1]. There have been an increasing number of studies focusing on complement and innate immune system proteins in relation to obesity, inflammation, and dyslipidemias [2,3,4]. Studies in humans have demonstrated that C3, the most abundant component of the complement cascade, and its mediator molecules are increased in obesity, metabolic syndrome and cardiovascular disease [2,5,6,7,8,9,10]. The central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease 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

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