Impact of maternal obesity on offspring hypothalamic neurocircuits: microRNA expression profiling of arcuate and paraventricular nuclei and associated outcomes

Abstract

Obesity is strongly associated with a variety of adverse health outcomes and the increase in childhood obesity is particularly alarming. More than 42 million children under 5 years of age are estimated to be overweight (World Health Organization) and childhood obesity tracks strongly with adolescent and adulthood obesity. Of particular concern is a growing prevalence of obesity in women of child-bearing age, as not only does this have health implications for herself, but it also has long-term effects on the health of the offspring. Due to the importance of maternal conditions for normal offspring development, situations of maternal undernutrition and maternal obesity can impair the offspring intrauterine growth and development. The phenotype of an individual can be driven by the in utero and early post-natal environmental conditions, such as the nutritional state of the mother. This has given rise to the notion of "developmental programming". Nutrient availability during intrauterine or perinatal periods can induce long-term metabolic and structural alterations, including permanent changes in brain development and increased risk of obesity. In light of the evidence demonstrating the importance of the intrauterine environment and its effects in offspring health, in the present project we aim to study the miRNA expression profile in arcuate and paraventricular nuclei of mouse offspring born to obese mothers. The arcuate and paraventricular nuclei are located in the hypothalamus, the central brain region mediating regulation of short-term and long-term dietary intake via the synthesis of various orexigenic and anorectic neuropeptides. Therefore, the results of these studies will help us understand the epigenetic mechanisms underlying the increased risk of obesity in offspring born to obese mothers.