Hypothalamic mechanisms of appetite regulation involve stress response and epigenetic modification

Appetite regulation is primarily mediated by the hypothalamus, within which many neurotransmitters that regulate feeding are shared by the stress response circuitry. Stressors, especially those occur during critical periods of life, influence epigenetic programming and gene expression in the long-term. Therefore, the aim of this dissertation was to elucidate how hypothalamic mechanisms of appetite regulation correlate with the stress response and epigenetic modifications, using avian models and intracerebroventricular administration of various appetite-regulating factors. We first administered two methylation modifiers, S-adenosylmethionine (SAM), a methyl donor, and 5-azacytidine (AZA), a methylation inhibitor, to determine their effects on appetite. When measuring food intake immediately post-injection, SAM didn't affect fed or fasted chickens from a line selected for low bodyweight (LWS, individuals with anorexia), but suppressed feeding in fed and fasted broilers. In Japanese quail, SAM transiently induced satiety in fed but not fasted chicks. Intriguingly, AZA increased feeding in fasted LWS but decreased it in fed chicks. While it didn't affect either fed or fasted broilers, AZA induced satiety in both fed and fasted quail. These results suggests that SAM/AZA can directly affect appetite depending on genetics and nutritional state. The LWS chickens, when injected with SAM or AZA on day of hatch, didn't show increased feeding to the orexigenic stimulation of neuropeptide Y central injection on day 5 post-hatch. This suggests that epigenetic modifications occurred following SAM/AZA injection and affect appetite regulation that persisted. In other studies, we injected broilers with prostaglandin E2 (PGE2) or β-melanocyte-stimulating hormone (β-MSH) since their effects on appetite are unknown in meat-type chicks. We found that they both potently induced satiety, but the effective duration was longer in β-MSH-injected birds (up to 9 hours) than in PGE2-injected chicks (lasted for 1.5 hours). They both activated the paraventricular nucleus of the hypothalamus. The satiety induced by β-MSH mainly involved corticotropin-releasing factor and mesotocin, while the effect of PGE2 included ghrelin and brain-derived neurotropic factor. Nevertheless, all affected appetite-related factors have connections with the stress response. Thus, our results demonstrate that the hypothalamic mechanisms underlying anorexia induced by different neuroactive molecules involve the stress response and epigenetic modifications.