Maternal high fat diet programming of the endocrine system.

The escalating rates of metabolic and cardiovascular diseases in modern society are due in part to recent environmental changes, such as increased availability of energy-dense food items and decreased necessity for physical exertion. Numerous epidemiological studies and animal models provide strong evidence that the environment experienced during early life programs persistent changes in the physiology of developing offspring. Maternal metabolic status and diet during gestation and lactation have a marked influence on the perinatal environment and a long-term impact on offspring's energy balance regulation and risk of developing metabolic and cardiovascular diseases (Sullivan et al. 2011). Programming by both maternal undernutrition and maternal overnutrition increases the offspring's risk of developing obesity and metabolic and cardiovascular diseases. Currently, the majority of women of reproductive age are overweight or obese (King, 2006) and consume a diet high in dietary fat; thus it is critical to understand the impact that maternal overnutrition and obesity have on developing offspring. Epidemiological studies and animal models of maternal overnutrition indicate that maternal obesity increases the incidence of obesity and metabolic syndrome in the next generation (Oken & Gillman, 2003; Sullivan et al., 2011). Moreover, increasing evidence implicates maternal obesity and high fat diet consumption in increasing the offspring's risk of developing diabetes, cardiovascular diseases, and even behavioral disorders such as anxiety, attention deficit hyperactivity disorder, and autism spectrum disorders. In the present issue of The Journal of Physiology, Franco and colleagues (2012) present novel and intriguing findings on the impact of maternal high fat diet (HFD) consumption on endocrine regulation in the offspring. This is the first paper to demonstrate that maternal HFD consumption results in increased adrenal catecholamines and thyroid hormones. The authors postulate that the perturbations in the endocrine system are due to the observed changes in the composition of the breast milk that the offspring consumed. The authors performed a well-designed study in which female Wistar rats were fed either a control (CTR) diet (9% of calories from fat) or an isocaloric HFD (28% of calories from fat). This is the first study to document the impact of a maternal isocaloric HFD consumption on offspring development, allowing examination of the impact of diet composition independent of increased caloric consumption. It is also important to note that the HFD was only moderately high in fat content (28% of calories) in contrast to most studies in which the HFD has between 50 and 60% of its calories in the form of fat. Females consumed the HFD for 8 weeks prior to conception and throughout gestation and lactation. Importantly, to control for differences in postnatal nutrition due to natural variations in litter size, all litters were adjusted to six males per dam. As expected, consumption of the isocaloric HFD resulted in an increased adiposity prior to pregnancy (Franco et al. 2012). Interestingly, the weight and adiposity of CTR and HFD dams were similar after lactation, which indicates that the HFD dams differentially regulate body weight during pregnancy and lactation. HFD consumption also markedly changed breast milk, resulting in an increase in lactose and triglyceride levels but lower levels of cholesterol at 11 days after birth as compared to CTR breast milk. At weaning, there was a higher concentration of protein, cholesterol, and triglycerides in HFD breast milk. These findings indicate that the offspring from HFD dams were exposed to overnutrition during early postnatal development, which may contribute to their increased body weight and adiposity at weaning. Corresponding with their increased adiposity, HFD offspring also exhibited hyperglycaemia, hyperleptinaemia, and signs of leptin resistance in the arcuate nucleus of the hypothalamus including a reduced ratio of pSTAT3 to STAT3 and decreased SOCS3 content, which may contribute to hyperphagia. An important and novel finding of this study is that maternal HFD consumption dramatically impacted the endocrine regulation of offspring at weaning. This is the first study to demonstrate that HFD offspring had higher adrenal catecholamine content and hyperactivity of the thyroid axis. Given the important roles that catecholamines and thyroid hormones have in regulating homeostatic processes especially in times of stress, alterations in these endocrine pathways will dramatically impact whole body physiology. For example, thyroid hormone is a critical regulator of both energy expenditure and energy intake and therefore has an important impact on body weight. In addition, both thyroid hormones and catecholamines are important regulators of blood glucose production and energy storage. Increased catecholamines are associated with increased blood pressure and heart rate (Trevenzoli et al. 2007). This is the first demonstration of an influence of maternal HFD on the endocrine regulation of the offspring, and it reveals how comprehensively offspring are impacted by maternal HFD consumption. The study by Franco et al. (2012) demonstrated an impact on the endocrine system in male offspring at weaning. It is critical that future studies follow up this finding by examining whether this endocrine dysfunction persists into adulthood. Also, as many animal studies observe sex differences in the impact of maternal nutrition on physiology and behavior (Sullivan et al. 2011), it is imperative that upcoming studies examine the impact of maternal HFD on the endocrine system in female offspring. A more detailed analysis of the impact of maternal diet on the regulation of other endocrine glands, such as the pituitary and gonads, also needs to be conducted. Franco et al. (2012) noted an impact of maternal HFD on thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus, and it will be interesting to determine which of the other hypothalamic peptides are also influenced by maternal diet. As these findings suggest that maternal diet influences behavior and physiology in part by impacting the endocrine regulation, it is important that future studies carefully document the impact of maternal HFD-induced endocrine dysfunction on diverse physiological and behavioral processes including energy balance regulation, reproduction, stress response, and anxiety-like behavior.