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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:589844 |
| Date | January 2013 |
| Creators | Sivakumar, Kavitha |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/58490/ |
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