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The impact of maternal obesity and gestational diabetes mellitus on adipose tissue and placental derived adipocytokines
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Sivakumar, Kavitha (2013) The impact of maternal obesity and gestational diabetes mellitus on adipose tissue and placental derived adipocytokines. MD thesis, University of Warwick.
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WRAP_THESIS_Sivakumar_2013.pdf - Submitted Version Download (4Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b2692656~S9
Abstract
Pregnancy; a natural insulin resistant state; becomes exaggerated when complicated
by obesity and gestational diabetes (GDM). Both obesity and GDM are associated
with severe maternal and fetal complications as well as with increased risks of
obesity in the offspring later in life. Little work has been performed on the levels of
adipokines in lean, obese and diabetic pregnancy. This study aimed to explore the
roles of three adipokines; namely, Adipsin, Acylation stimulating protein and
Fibroblast Growth Factor-21, all of which are involved in insulin resistant and
dysmetabolic states such as obesity and type 2 DM. We hypothesized that these
adipokines might play a role in pregnancy. A cohort of Caucasian pregnant women
undergoing elective caesarean section was studied. Clinical parameters were assayed
as well as circulating maternal and fetal levels of adipsin, ASP and FGF21. Paired
samples of fat and placental tissue were taken for explant studies to measure secreted
Adipsin, ASP and FGF21 levels. Cord levels of adipsin and ASP were significantly
elevated in the offspring of obese and diabetic mothers compared to their lean
controls. Plasma FGF21 levels were significantly higher in GDM compared to lean
controls. FGF21 levels in cerebrospinal fluid (CSF) were also measured and a
CSF/Plasma ratio calculated.
I have identified the human placenta as a source of adipsin, ASP and FGF21. More
specifically, I have shown that placental Hofbauer cells (macrophages) produce
adipsin and ASP. This is the first time secretion of adipsin and ASP by Hofbauer
cells has been demonstrated. I conjecture a role of these macrophages in lipid
metabolism at the materno-fetal interface. Also, I describe that GDM mothers have
higher CSF FGF21 as compared to controls but the CSF:plasma ratio of FGF21 was
lower in GDM mothers, potentially suggesting an alternative reason for and
contributing to hyperglycaemia in GDM.
Item Type: | Thesis (MD) |
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Subjects: | Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics |
Library of Congress Subject Headings (LCSH): | Adipose tissues, Diabetes in pregnancy, Obesity -- Physiological aspects, Pregnancy -- Complications |
Official Date: | April 2013 |
Institution: | University of Warwick |
Theses Department: | Warwick Medical School |
Thesis Type: | MD |
Publication Status: | Unpublished |
Supervisor(s)/Advisor: | Vatish, Manu; Randeva, Harpal S. |
Description: | [Journal articles in appendix removed for copyright reasons]. |
Extent: | 1 volume (various pagings) : charts. |
Language: | eng |
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