EARLY DEVELOPMENTAL ELEVATED DIETARY FAT EXPOSURE IMPACTS ON BRAIN ACTIVITY: RESPONSE TO ACUTE DIETARY AND PHARMACOLOGICAL INTERVENTIONS IN ADULTHOOD

The brain primarily regulates energy balance through the central melanocortin system. We aimed to understand the role of the paraventricular nucleus of the thalamus (PVT), a brain region involved in integrating energy state with behavior, and how early nutritional influences impact this system. The melanocortin-3-receptor (MC3R), a key player, is highly expressed within the PVT. We investigated the effects of early overnutrition and how it impacts MC3R neuronal development and activity. Using a mouse model of maternal overnutrition, we probed effects in the offspring animals across the lifespan. We visualized neuropeptides, axonal projections and neuronal activation. Adult offspring were then challenged with either a high-fat diet (48 hrs), fasting-refeeding or pharmacological intervention with Setmelanotide (an alpha-melanocyte stimulating hormone (α-MSH) mimetic) either systemically or directly in the PVT. We identified a role of early maternal overnutrition in impacting the maintenance of projections to the PVT and assessed changes in neuronal and whole-body physiological response. This research highlights the crucial role of early nutrition in shaping the brain’s response to metabolic challenges. Further study of PVT MC3R will improve our understanding of offspring feeding behaviors impacted by maternal diet. More research is needed to explore these findings in humans and how early nutrition can impact adult brain responses.