Endocrine Abstracts

Obesity prevalence is increasing across the globe. This includes women of childbearing age with recent statistics reporting that over half of women are now either overweight or obese during pregnancy in the UK. This is accompanied by an increased prevalence of gestational diabetes with some reports suggesting that one in seven babies in the world are born from a diabetic pregnancy. This is a major concern as evidence from humans and animal models suggests that developing in utero in an obesogenic or diabetic environment has a long-term impact on the metabolic and cardiovascular health of the child. This is termed the developmental origins of health and disease. The strongest evidence from humans to support the idea that development in utero in an obesogenic environment ‘programmes’ increased risk of obesity and cardio-metabolic disease comes from studies of siblings born before and after maternal bariatric surgery. These revealed that the sibling born post-surgery had reduced adiposity, lower blood pressure and increased insulin sensitivity compared to their sibling born prior to maternal weight-reducing surgery. We have used a mouse model of maternal diet-induced obesity to define the mechanisms by which obesity/impaired glucose tolerance during pregnancy impacts on the long-term cardio-metabolic health of the offspring. These studies showed that the offspring of obese dams, with impaired glucose tolerance during pregnancy, develop insulin resistance, cardiac dysfunction, hypertension and fatty liver even when the offspring are lean. The insulin resistance is associated with cell autonomous post-transcriptional programming of insulin signalling protein expression. In addition offspring of obese dams are more susceptible to diet-induced obesity. We identified maternal hyperinsulinaemia as a key ‘programming’ factor thus highlighting it as an important target of intervention studies such as those involving increased maternal physical activity.