Early overfeeding and adult anhedonia: Impact of neonatal nutrition on hedonic food regulation in male rats.

The aim of our study was to analyze the impact of early-life overnutrition and the exposure in adulthood to a cafeteria diet (CAF) on eating behavior and on the expression of key genes involved in the regulation of food intake. Male Wistar rats were raised in small (SL, 4 pups/dam) or normal litters (NL, 10 pups/dam), fed a control diet (CON) until postnatal day (PND) 90. Then, they received CON or CAF for 11 weeks (NL-CON, NL-CAF, SL-CON, SL-CAF; 12±2 rats/group). Body weight, food intake and behavioral tests (Elevated Plus Maze: EPM, Sensory-specific satiety: SSS) were assessed. At PND167, the rats were euthanized to obtain brain, blood and fat pads. Ventral tegmental area (VTA), Nucleus Accumbens (NAc) and Arcuate Nucleus (Arc), were isolated by micropunch technique for qPCR analysis. Early overfeeding alone had the ability to alter long-term SSS. CAF groups showed increased body weight, adiposity and energy intake; sweet food preference and altered SSS. SL-CAF showed hypophagia, basal hyperglycemia, altered SSS and anxiety-like behavior. Both NL-CAF and SL-CAF showed antidopaminergic effects, but through different pathways: NL-CAF reduced dopamine (DA) production in VTA via decreased tyrosine hydroxylase (TH) expression, while SL-CAF exhibited an increase in dopamine active transporter (DAT) expression in NAc enhancing clearance. SL decreased Neuropeptide Y (NPY) expression in the Arc in adulthood, which has been proposed to be the link between homeostatic and hedonic systems. Our research reveals a key link between early-life overnutrition and adult hedonic feeding control, emphasizing its lasting impact on eating behavior and the potential for innovative therapeutics to combat obesity.