Development, brain plasticity and reward: early high-fat diet exposure confers vulnerability to obesity—view from the chair

Abstract

The significant increase in childhood obesity has become a particular concern, and it is recognized that the programming of obesity can arise from events occurring in the peri-conception period, prenatally and/or during the early postnatal period. In particular, high intake of dietary fat by the mother has long-term effects that are worse than once thought. This symposium was designed to outline some of the important consequences of maternal high-fat feeding during gestation and lactation, as well as exposure to a high-fat diet (HFD) after weaning, on the programming of homeostatic and hedonic regulation of food intake in both rodents and nonhuman primates (NHPs). Although a consensus emerges that high-fat feeding in early development increases the risk of developing obesity and the metabolic syndrome in adulthood, there is less agreement on the mechanisms through which this risk is conferred. Epigenetic modifications in specific gene promoters within the dopaminergic reward pathways and on the histone code will be discussed. We will also examine the effects of metabolic hormones such as leptin and ghrelin to shape the early development of hypothalamic projections that are critical to control food intake; finally, the importance of placental function in increasing obesity risk in NHP fetus from HFD mothers will be debated.

Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring

“…A consensus has emerged that early life exposure to a maternal obesogenic environment increases the risk of developing obesity and metabolic disorders in adulthood. However, there is less agreement on the mechanisms through which such risk may be conferred ( 4 ). Collectively, data to date reveal that leptin, in particular, and ghrelin play key roles in facilitating the normal development of hypothalamic neural circuits and suggest that normal expression of these factors during the fetal/neonatal period is key for lifelong metabolic regulation ( 55 , 86 , 102 ).…”

“…In addition to homeostatic systems responsive to nutrient sensing and regulation of energy balance, maternal obesity can also perturb the hedonic system which includes stimuli related to reward and cognitive factors ( 4 ). In the context of early life developmental programming, exposure to HF/high-sugar diets has been shown to result in altered development of central reward systems, leading to increases in fat intake and altered responsiveness of the hedonic reward system to over consumption of energy-dense food in offspring in later life ( 32 ).…”

“…Many of the perinatal exposures examined experimentally are associated with reorganization of neurodevelopmental pathways that play a role in energy expenditure and appetite regulation in ways that increase the later risk for obesity and related metabolic dysfunction in offspring ( 3 ). Although a consensus has been reached that an obesogenic environment in the periconceptual, pregnancy and lactation periods increases the risk of metabolic disorders in adulthood, the potential mechanisms that confer this increased risk are less well defined ( 4 ). One of the most investigated (and experimentally consistent) mechanisms is around that of altered development of the hypothalamus during critical periods of developmental plasticity.…”

A gestational diet high in fat-soluble vitamins alters expression of genes in brain pathways and reduces sucrose preference, but not food intake, in Wistar male rat offspring

“…The upregulation of both anorexogenic and orexogenic genes may just explain the absence of changes on food intake and body weight observed in previous studies (Cho et al 2013a;Cho et al 2014). Moreover, gene changes were not sustained across weaning and postweaning, which may only indicate brain plasticity during different windows of development (Hanson et al 2011;Walker 2012).…”

Obesity and Related Type 2 Diabetes: A Failure of the Autonomic Nervous System Controlling Gastrointestinal Function?

“…In animal models, it has also been shown that a change in synaptic activation (synaptic plasticity) is induced in the reward system [16] followed by an inadequate response to the consumption of highly energetic food in concomitance with the pregnancy period [10,25]. This is due to the epigenetic alteration of the expression of dopamine and opioid-related genes present in the mesocorticolimbic circuits [26].…”