Effect of obesity on the complement response to OFTT
We subsequently divided the PCOS and control groups into ‘obese’ (BMI ≥
30 kg/m2) and ‘non-obese’ (BMI <30
kg/m2) groups, and compared the effects of lipaemia on
plasma levels of factor H, TCC and C3 in these groups (figure 3a-c
respectively). Within the PCOS group, obesity had a profound effect on
both baseline levels and AUC for factor H. Fasting factor H levels and
AUC were both markedly increased in obese versus non-obese PCOS subjects
(mean±SEM; baseline: 362.1±56.41
µg/ml versus 204.3±24.05 µg/ml
respectively; p<0.001, and AUC: 1717±164.1 µg min/ml versus
1004±54.4 µg min/ml respectively; p<0.0001). Furthermore,
across the whole cohort, strong correlations were observed between
factor H AUC and each of HOMA-IR, visceral and subcutaneous fat area
(Figure S1; p<0.0001 for all), and in fasting samples (cohort
1) between factor H and BMI, regardless of age (Figure S2; age 20-30:
r2 0.43, p< 0.001 [PCOS]
r2 0.62, p< 0.001 [controls]; age 30-40:
r2 0.30, p< 0.001 [PCOS]
r2 0.44, p< 0.001 [controls]; age 40-50:
r2 0.77, p< 0.05 [PCOS],
r2 0.36, p<0.001 [controls]). The TCC
response to OFTT was also greater at 120 minutes in obese compared to
non-obese PCOS subjects (figure 3b; mean±SEM: 0.54±0.12 µg/ml versus
0.29±0.04 µg/ml respectively; p<0.05). In contrast, no
significant differences were observed in factor H and TCC OFTT responses
between lean and obese controls. Baseline C3 levels and C3 AUC were
significantly increased in obese compared to non-obese subjects
irrespective of disease status, with C3 concentrations increasing
gradually across the time course of the OFTT in both groups (Figure 3c).