Perinatal And Intergenerational Influences On Adult Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
The aim of this project is to determine the effects of restriction of nutrient supply before and after birth on growth and the development of adult onset diabetes. Being born small and its associated neonatal catch-up growth independently predict adult diabetes. Placental restriction is a major cause of reduced nutrition and growth before birth and is implicated in this programming of disease. Our novel findings suggest that placental compromise increases appetite but also impairs milk quality a ....The aim of this project is to determine the effects of restriction of nutrient supply before and after birth on growth and the development of adult onset diabetes. Being born small and its associated neonatal catch-up growth independently predict adult diabetes. Placental restriction is a major cause of reduced nutrition and growth before birth and is implicated in this programming of disease. Our novel findings suggest that placental compromise increases appetite but also impairs milk quality and supply which limits overfeeding and catch-up growth initially, but on weaning, may independently lead to diabetes. We will determine if this is a direct result of poor nutrition and made worse by overfeeding in response to restored nutrition. We hypothesize that placental compromise permanently reduces an individual's metabolic capacity and that the extent of availability of nutrition after birth determines the consequences for insulin action and increased body fat. Manipulations of postnatal nutrition (by cross-fostering) and fat oxidation will be performed, which are pivotal to understanding the roles of catch-up growth and increased food intake in disease onset. We have found that cross-fostering small rat pups at birth onto mothers with normal lactation improves growth during lactation. The proposed studies will establish the cross-fostering effect on the development of diabetes and identify a developmental stage during which nutritional or other manipulations may have beneficial consequences for the health of the breastfeeding small infant. We propose to determine whether adult females, exposed to placental restriction as a fetus, produce offspring that develop diabetes, and establish whether this effect is caused by programming before conception and-or an altered fetal environment. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health.Read moreRead less
Prenatal Placental And Postnatal Mammary Programming Of Cardiovascular And Renal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$503,776.00
Summary
Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat mo ....Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat model, we will determine for the first time if restricted nutrition before birth via the placenta or after birth via lactation increases the risk of developing high blood pressue and kidney and blood vessel dysfunction. Manipulations of nutrition after birth will be achieved by cross-fostering studies. We will establish whether a reduction in the number of functioning units (nephrons) in the kidney, alterations in key genes involved in kidney development and changes in blood vessel reactivity are associated with developing hypertension. We will manipulate the renin-angiotensin system (RAS), which is important in determining kidney function, to define its role in hypertension in this model. We propose that a common lifestyle insult, such as modest elevation in dietary salt, will evoke exaggerated responses in adult offspring who were born small. These studies will identify the mechanisms by which the kidney, vasculature and RAS contribute to the programming of hypertension and the relative roles of the prenatal and postnatal environments. Defining the underlying mechanisms responsible will provide insight into early life interventions that may lessen these adverse consequences for longer-term health. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health in this emerging field.Read moreRead less