Diet-induced obesity and exercise during pregnancy: consequences for maternal and offspring
metabolic health
Dr Sue Ozanne, Institute of Metabolic Science and Professor Abby Fowden, Department of
Physiology, Development and Neuroscience (PDN)
In developed countries, women of reproductive age are becoming increasingly obese. Even those of
normal body mass index are gaining excess weight during pregnancy, primarily as fat. Human
epidemiological observations and experimental animal studies have shown that enhanced fat
deposition and obesity during pregnancy are associated with abnormal birth weight and an
increased risk of the offspring developing obesity and metabolic disease in later life. However, the
mechanisms operating during pregnancy that underlie these detrimental outcomes remain largely
unknown. Nor is it clear whether interventions advocated to combat the metabolic dysfunction of
obesity, such as increased exercise, are beneficial to the growth and development of the fetus in
either normal or obese mothers. 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 the allocation
of nutrients to conceptus growth in mice using a combination of in vivo and in vitro techniques. 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? These questions will be addressed using a mouse model of maternal
diet-induced obesity. The project will incorporate studies at the whole body (e.g. glucose tolerance,
insulin sensitivity, body composition), tissue (e.g. placental nutrient transfer, tissue glucose uptake)
and molecular (e.g insulin signalling pathway and miRNA analysis) levels. The project, therefore,
provides unique training in both in vivo physiological measurements (e.g three-pool tracer
methodology, hyperinsulinaemic-euglycaemic clamps, TDNMR), stereological analyses of tissue (e.g.
placental vessel volumes, surfaces areas) and in vitro molecular techniques including Western
blotting, RT-PCR and ELISA.
All the facilities and techniques needed for this interdisciplinary project are available in the Ozanne
(Metabolic Research Laboratories) and Fowden (PDN and Centre for Trophoblast Research)
laboratories). The project sits centrally within the World Class Bioscience theme of the BBSRC and
straddles two of its strategic priorities, Food, nutrition and health and healthy ageing across the
lifecourse.