Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy

Huda, S. S., Jordan, F., Bray, J., Love, G., Payne, R., Sattar, N. and Freeman, D. J. (2017) Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy. Clinical Science, 131(13), pp. 1529-1540. (doi: 10.1042/CS20160832) (PMID:28566469) (PMCID:PMC6376613)

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Abstract

Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In pre-eclampsia only, visceral adipose tissue TNFα release was increased after lipopolysaccharide stimulation (57 [76] vs 81 [97] pg/mL/ug DNA, p=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r=-0.61, p=0.030) in pre-eclampsia. Visceral adipocyte IL-6 release was increased after lipopolysaccharide stimulation in pre-eclampsia only (566 [696] vs 852 [914] pg/mL/ugDNA, p=0.019). Visceral adipocyte CCL-2 basal (67 [61] vs 187 [219] pg/mL/ugDNA, p=0.049) and stimulated (46 [46] vs 224 [271] pg/mL/ugDNA, p=0.003) release was greater than in subcutaneous adipocytes in pre-eclampsia only. In pre-eclampsia, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] vs 0.8 [0.00-1.27] TNF / PPIA ratio, p=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] vs 51.0[29.9] CSF1R/PPIA ratio, p=0.011) and activated (cfms+) macrophage count (6.7[2.6] vs 15.2[8.8] % cfms+/adipocyte, p=0.031) were higher in pre-eclampsia than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia.

Item Type:Articles
Keywords:Adipocytes, adipokines, preeclampsia, pregnancy.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Freeman, Dr Dilys and Bray, Mr Jack and Jordan, Mrs Fiona and Sattar, Professor Naveed and Huda, Dr Shahzya
Authors: Huda, S. S., Jordan, F., Bray, J., Love, G., Payne, R., Sattar, N., and Freeman, D. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Published Online:28 June 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Clinical Science 131(13):1529-1540
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
366741Adipocyte lipolysis as a candidate pathway in the pathogenesis of pre-eclampsiaNaveed SattarBritish Heart Foundation (BHF)PG/03/147/16351RI CARDIOVASCULAR & MEDICAL SCIENCES
484711To compare phagocytic function and uptake of PrPSc by macrophages from scrapie susceptible and resistant sheepFiona HoustonWellcome Trust (WELLCOTR)086656/Z/08/ZVET - PATHOLOGY, PUBLIC H & DISEASE INV