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Diet-induced obesity and exercise during pregnancy: consequences for maternal and offspring metabolic health (Abigail Fowden, Susan E. Ozanne)

Supervisors: Abigail Fowden, Susan E. Ozanne

In developed countries, women of reproductive age are becoming increasingly obese and gaining excess weight as fat during pregnancy. Studies in human populations and experimental animals have shown that obesity and increased fat accumulation during pregnancy lead to abnormal birth weight and an increased risk of offspring obesity and metabolic dysfunction in later life. However, the mechanisms underlying these detrimental outcomes remain largely unknown. Nor is it clear whether interventions advocated to combat the metabolic complications of obesity, such as exercise, are beneficial to fetal development. The aim of this project is to investigate the effects of diet-induced obesity coupled with exercise on the maternal metabolic adaptation to pregnancy and nutrient allocation to conceptus growth in mice. The project is designed to answer three specific questions: 1) what effects does diet-induced obesity have on the maternal metabolic adaptation to pregnancy? 2) how are these adaptations altered by exercise in normal and obese mothers? and 3) what are the immediate and long-term consequences of maternal diet-induced obesity and exercise on the offspring, including the phenotype of the placenta, the organ responsible for metabolic demand signalling to the mother and for supplying nutrient resources to the fetus? The project will incorporate studies at the whole body (e.g. glucose tolerance, insulin sensitivity, three-pool tracer methodology,body composition), tissue (e.g. placental nutrient transfer, tissue glucose uptake, tissue morphology by stereology) and molecular (e.g insulin signalling pathway proteins and microRNA analysis) levels. The project, therefore, provides unique training in both in vivo physiological measurements and in vitro morphological and molecular analyses.

Relevant references

Sferruzzi-Perri, A.N., et al., (2013). An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J 27 3928-3937.

Alfraidhi, M., et al., (2014). Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity. Am. J. Physiol. 307 R26-R34.

Burton, G.J. & Fowden, A.L. (2015). The placenta: a multifaceted, transient organ. Phil. Trans. Roy. Soc. B 370 20140066.

 

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