Endocrine Abstracts

Strong evidence from studies in humans and animal models suggests that the nutritional environment to which a developing fetus is exposed impacts on long-term cardio-metabolic health. This concept has been termed nutritional programming. Although initial focus was on the detrimental consequences of fetal under-nutrition, the growing prevalence of obesity across the globe has focussed attention towards fetal over-nutrition. Obesity prevalence is increasing in all age groups, including women of childbearing age. In many populations over half of women are now either overweight or obese during pregnancy and this is accompanied by an increased prevalence of gestational diabetes. This is of major concern as evidence suggests that developing in utero in an obesogenic/diabetic environment has both immediate and long-term impacts on the health of the mother and child. The strongest evidence from humans to suggest that development in utero in an obesogenic environment “programmes” increased risk of obesity and cardio-metabolic disease comes from the study 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 show that the offspring of obese dams develop insulin resistance, cardiac dysfunction, hypertension and fatty liver even when the offspring are lean. We have identified maternal hyperinsulinaemia as a key ’programming” factor and shown that insulin resistance in some tissues can occur in utero. These findings highlight maternal hyperinsulinaemia as an important target of intervention studies such as those involving increased maternal physical activity to reduce the transmission of poor cardio-metabolic health between mother and child.