Complement activation in polycystic ovary syndrome occurs in the postprandial and fasted state and is influenced by obesity and insulin sensitivity

Objective Polycystic ovary syndrome (PCOS) is associated with metabolic risk. Complement proteins regulate inflammation and lipid clearance but their role in PCOS‐associated metabolic risk is unclear. We sought to establish whether the complement system is activated in PCOS in the fasting and postpr...

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Published in:Clinical endocrinology (Oxford) Vol. 94; no. 1; pp. 74 - 84
Main Authors: Lewis, Ruth D., Narayanaswamy, Anil K., Farewell, Daniel, Rees, Dafydd Aled
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01.01.2021
John Wiley and Sons Inc
Subjects:
Complement activation
Complement component C3
Complement component C4
Complement component C5
Complement component C5a
Complement factor H
complement system proteins
Fasting
Insulin
Insulin resistance
Laboratory testing
Metabolism
Obesity
Original
Ovaries
Polycystic ovary syndrome
Properdin
complement system proteins
insulin resistance
obesity
polycystic ovary syndrome
ISSN:0300-0664, 1365-2265, 1365-2265
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Summary:Objective Polycystic ovary syndrome (PCOS) is associated with metabolic risk. Complement proteins regulate inflammation and lipid clearance but their role in PCOS‐associated metabolic risk is unclear. We sought to establish whether the complement system is activated in PCOS in the fasting and postprandial state. Design Case‐control study. Patients Fasting complement levels were measured in 84 women with PCOS and 95 healthy controls. Complement activation post‐oral fat tolerance test (OFTT) was compared in 40 additional subjects (20 PCOS, 20 controls). Measurements Activation pathway (C3, C4, C3a(desArg), factor B, factor H, properdin, Factor D) and terminal pathway (C5, C5a, terminal complement complex [TCC]) proteins were measured by commercial or in‐house assays. Results Fasting C3, C3a(desArg) and TCC concentrations were increased in insulin‐resistant (adjusted differences: C3 0.13 g/L [95%CI 0‐0.25]; C3a(desArg) 319.2 ng/mL [19.5‐619]; TCC 0.66 μg/mL [0.04‐1.28]) but not in insulin‐sensitive women with PCOS. C3 and factor H levels increased with obesity. Post‐OFTT, C3 and C4 levels increased to a similar extent in PCOS subjects and controls, whist factor H levels increased more in women with PCOS compared to controls (adjusted differences (area under the curve): 12 167 μg min/mL [4942‐19 392]), particularly in the presence of concomitant obesity. Conclusions Activation and terminal complement pathway components are elevated in patients with PCOS, especially in the presence of insulin resistance and obesity.
Bibliography:Funding information
This work was supported by the Wellcome Trust through ISSF funding awarded to Cardiff University. Measurement of C3 and C4 (cohort 2) and manuscript preparation were carried out under the auspices of British Heart Foundation project grant (PG/13/28/29833) awarded to Dr Timothy Hughes (Cardiff University).
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ISSN:0300-0664
1365-2265
1365-2265
DOI:10.1111/cen.14322