Högskolan i Skövde

Obesity during pregnancy (a BMI of 30kg/m2 and over) is a key risk factor for a number of diseases including gestational diabetes. It is thought that mothers who are obese tend to give birth to babies who are large for their gestational age (LGA) and potentially more susceptible further health complications during early childhood and beyond. As approximately 2/3 of women in the USA are entering pregnancy as overweight (BMI > 25) or obese the possibility of creating a vicious cycle of intra-uterine transmission of metabolic disease inherited from the mother to child is a growing problem. Pregnant women with low concentrations of circulating adiponectin (APN) in their first trimester are more likely to develop gestational diabetes than patients with normal levels, implying a causal link to insulin resistivity. Obese pregnant women who have lower APN levels have a difficulty controlling placental homeostasis and this is thought to cause perturbations in the maternal-supply/fetal-demand model leading to excess fetal nutrients. This study aimed to investigate the effects of APN on placental gene expression of nutrient transporters. Results show that over-abundance of circulating APN where both dams and fetuses are APN transgenic, show significantly increased placental estrogen receptor-α expression and lower expression when that same genotype is exposed to a high-fat/high-sucrose diet. Over-abundance of APN also appears to normalize expression of SNAT2 and LPL as a deficiency in APN appears to cause reduced SNAT2 expression and compensatory LPL expression. As fetal weights were not increased in obese pregnancies in either strain of dams yet placenta weights generally increased, there appears to be an APN-independent mechanism working in knockout placentas to protect the fetus from excess growth alongside a possible disconnect between mTOR and SNAT2 signalling. In conclusion, there are still undiscovered mechanisms protecting the fetus against overgrowth in mice that don’t produce APN. It is also evident that mice that had higher levels of APN were protected against excess nutrient transport in obese diets and that APN likely ensures optimal concentrations of each nutrient type reach the fetus.