Maternal and postnatal high-fat diet consumption programs energy balance and hypothalamic melanocortin signaling in nonhuman primate offspring.

Maternal high-fat-diet (HFD) consumption during pregnancy decreased fetal body weight and impacted development of hypothalamic melanocortin neural circuitry in nonhuman primate offspring. We investigated whether these impairments during gestation persisted in juvenile offspring and examined the interaction between maternal and early postnatal HFD consumption. Adult dams consumed either a control diet (CTR; 15% calories from fat) or a high-saturated-fat diet (HFD; 37% calories from fat) during pregnancy. Offspring were weaned onto a CTR or HFD at ~8 mo of age. Offspring from HFD-fed dams displayed early catch-up growth and elevated body weight at 6 and 13 mo of age. Maternal and postnatal HFD exposure reduced the amount of agouti-related peptide fibers in the paraventricular nucleus of the hypothalamus. Postnatal HFD consumption also decreased the amount of agouti-related peptide fibers in the arcuate nucleus of the hypothalamus. Postnatal HFD was associated with decreased food intake and increased activity. These results support and extend our previous findings of maternal diet effects on fetal development and reveal, for the first time in a nonhuman primate model, that maternal HFD-induced disturbances in offspring body weight regulation extended past gestation into the juvenile period. Maternal HFD consumption increases the risk for offspring developing obesity, with the developmental timing of HFD exposure differentially impacting the melanocortin system and energy balance regulation. The present findings provide translational insight into human clinical populations, suggesting that profound health consequences may await individuals later in life following intrauterine and postnatal HFD exposure.

Maternal high-fat diet programming of the neuroendocrine system and behavior.

This article is part of a Special Issue "SBN 2014". Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic-pituitary-adrenal (HPA) axis.

Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates.

Perinatal exposure to maternal obesity and high-fat diet (HFD) consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning) was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations.

Ecology, Fitness, Evolution: New Perspectives on Categorization.

Categorization's great debate has weighed single-system exemplar theory against the possibility of alternative processing systems. We take an evolutionary perspective toward this debate to illuminate it in a new way. Animals are crucial behavioral ambassadors to this area. They reveal the roots of human categorization, the basic assumptions of vertebrates entering category tasks, and the surprising weakness of exemplar memory as a category-learning strategy. These results have joined neuroscience results to prompt important changes in categorization theory. Categorization's great debate is ending. Categorization is served by multiple systems of process and representation.

Categorization: The View from Animal Cognition.

Exemplar, prototype, and rule theory have organized much of the enormous literature on categorization. From this theoretical foundation have arisen the two primary debates in the literature-the prototype-exemplar debate and the single system-multiple systems debate. We review these theories and debates. Then, we examine the contribution that animal-cognition studies have made to them. Animals have been crucial behavioral ambassadors to the literature on categorization. They reveal the roots of human categorization, the basic assumptions of vertebrates entering category tasks, the surprising weakness of exemplar memory as a category-learning strategy. They show that a unitary exemplar theory of categorization is insufficient to explain human and animal categorization. They show that a multiple-systems theoretical account-encompassing exemplars, prototypes, and rules-will be required for a complete explanation. They show the value of a fitness perspective in understanding categorization, and the value of giving categorization an evolutionary depth and phylogenetic breadth. They raise important questions about the internal similarity structure of natural kinds and categories. They demonstrate strong continuities with humans in categorization, but discontinuities, too. Categorization's great debates are resolving themselves, and to these resolutions animals have made crucial contributions.

Maternal high-fat diet and obesity impact palatable food intake and dopamine signaling in nonhuman primate offspring.

OBJECTIVE: To utilize a nonhuman primate model to examine the impact of maternal high-fat diet (HFD) consumption and pre-pregnancy obesity on offspring intake of palatable food and to examine whether maternal HFD consumption impaired development of the dopamine system, critical for the regulation of hedonic feeding. METHODS: The impact of exposure to maternal HFD and obesity on offspring consumption of diets of varying composition was assessed after weaning. The influence of maternal HFD consumption on the development of the prefrontal cortex-dopaminergic system at 13 months of age was also examined. RESULTS: During a preference test, offspring exposed to maternal HFD consumption and obesity displayed increased intake of food high in fat and sugar content relative to offspring from lean control mothers. Maternal HFD consumption suppressed offspring dopamine signaling (as assessed by immunohistochemistry) relative to control offspring. Specifically, there was decreased abundance of dopamine fibers and of dopamine receptor 1 and 2 proteins. CONCLUSIONS: This study reveals that offspring exposed to both maternal HFD consumption and maternal obesity during early development are at increased risk for obesity due to overconsumption of palatable energy-dense food, a behavior that may be related to reduced central dopamine signaling.

The impact of leptin on perinatal development and psychopathology.

Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as anti-psychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including autism spectrum disorders and Rhett disorder. Further, studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations.