The Influence of Maternal Obesity on Offspring Cardiovascular Control and Insights from Rodent Models

Abstract

Human cohort studies of mother-child associations around pregnancy suggest that pre-pregnancy body mass index (BMI) is causally associated with cardiometabolic risk factors in young adult offspring. Corroborative evidence in mammals for the influence of maternal obesity on offspring cardiovascular function is provided by obese pregnancy models in sheep and non-human primates, whilst more mechanistic studies in rodents suggest that perinatal exposure to the metabolic and hormonal milieu of maternal obesity may permanently change the central regulatory pathways involved in cardiovascular development and control. Shared central pathways of leptin and insulin signalling play an important role in the hypothalamic control of appetite and energy expenditure via sympathetic innervation of metabolically and thermogenically active tissues such as brown adipose tissue (BAT), but are also involved in sympathetic activation of non-thermogenic tissues, including the kidney, and central selective leptin sensitivity is implicated in obesity-related hypertension. In rodent studies, maternal obesity confers persistent sympathoexcitatory hyper-responsiveness and hypertension to the exposed offspring which appears to be mediated by neonatal hyperleptinaemia associated with permanently altered hypothalamic structure and function. Indeed, the neurotrophic role of leptin in hypothalamic development and aberrant cardiovascular control is evidenced by a rat model of experimental neonatal hyperleptinaemia in which leptin administration in naive pups during the critical period of postnatal hypothalamic plasticity leads directly to permanent cardiovascular dysregulation and hypertension. This chapter will discuss the epidemiological evidence and mechanistic insight from rodent studies on the influence of maternal obesity on offspring cardiovascular control.