Downregulation of Complement C3 and C3aR Expression in Subcutaneous Adipose Tissue in Obese Women

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.

Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse

“…In the former, the mRNA was detected mostly in the heart and the lung, and to a lesser extent in the kidney, liver, skeletal muscles, and adipose tissue, but not in the brain and the spleen (10,11). In humans, C3AR1 mRNA was found in large amounts in lung, spleen, small intestine, peripheral blood leukocytes, s.c. adipose tissue, and at low levels in the kidney and heart but not in the brain (5,6,71). Our data obtained with the tdTomato-C3aR knock-in mouse confirmed the presence of C3aR expression in the lung and VAT.…”

Red pitaya juice supplementation ameliorates energy balance homeostasis by modulating obesity-related genes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats

“…It is fascinating that the C3 expression decreases with obesity in the present study given that C3 mRNA expression levels typically positively correlated with obesity. Nevertheless, this finding is in agreement with recent discovery by Gupta et al [ 30 ] whereby they found down-regulation of complement C3 in subcutaneous tissue of obese women.…”

Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion

“…Plasma levels of these proteins are also excellent predictors of obesity, with PAI-1 being one of the top 5 circulating biochemical predictors of total, abdominal, visceral and liver fat 23 . Plasma PAI-1 activity is strongly correlated with elevated plasma triglyceride levels while plasma levels of complement protein 3a (C3a) increase with increasing level of obesity 24,25 . Given the separate association of coagulation and complement abnormalities with both adiposity and PGD after transplant, dysregulation of these pathways in thoracic VAT is an intriguing potential mechanism for the association of adiposity with PGD after lung transplantation.…”