Role of Hypothalamic Transforming Growth Factor-ß (TGF-ß)/Smad Signaling in Feeding Regulation in Chickens.

Previous studies in mammalian obesity models have suggested that central transforming growth factor-ß (TGF-ß) controls the gene expression of appetite-regulating neuropeptides and peripheral energy metabolism. In the present study, we investigated the possible involvement of central TGF-ß/Smad signaling in feeding regulation in chickens. Central administration of TGF-ß1 resulted in phosphorylation of Smad2 in the hypothalamus of chicks and suppressed feed intake without changing the gene expression of hypothalamic appetite-regulating neuropeptides (neuropeptide Y, agouti-related protein, proopiomelanocortin, and corticotropin-releasing factor). However, neither fasting nor refeeding induced the phosphorylation of hypothalamic Smad2. These findings suggest that the activation of hypothalamic TGF-ß/Smad signaling suppresses feed intake in chicks but it might not occur in response to feeding status.

Central administration of insulin and refeeding lead to Akt and ERK phosphorylation in the chicken medulla.

The purpose of this study was to investigate whether medullary cellular signaling pathways contribute to feeding regulation in chickens. Fasting inhibited the phosphorylated protein and its rates of ERK but not Akt in the chicken medulla, while refeeding promoted Akt and ERK. Intraperitoneal administration of sulfate cholecystokinin 8 did not affect medullary Akt and ERK phosphorylation in chickens. Intracerebroventricular administration of insulin significantly induced the phosphorylation of Akt and ERK in the chicken medulla. These findings suggest that the medullary Akt and ERK pathways are involved in the appetite-suppressive pathway of insulin in chickens.

Central administration of insulin and refeeding lead to the phosphorylation of AKT, but not FOXO1, in the hypothalamus of broiler chicks.

Several studies in rodents and layer chickens have demonstrated that insulin upregulates hypothalamic AKT-mediated signaling and expression of proopiomelanocortin (POMC, the precursor of alpha-melanocyte stimulating hormone, an anorexigenic peptide) and suppresses appetite in these animals. However, a previous study has also reported that insulin fails to suppress food intake in broiler chicks. In the present study, no significant differences were observed in hypothalamic AKT and forkhead box O1 (FOXO1) phosphorylation levels between broiler and layer chicks. The phosphorylation rate of AKT, but not that of FOXO1, increased in the hypothalami of broilers refed for 1 h after a 24-h fast, with a corresponding increase in plasma insulin concentration. Intracerebroventricular (ICV) administration of 50 pmol insulin, which could decrease food intake in broiler chicks, significantly increased the AKT phosphorylation rate, whereas no significant change was observed in FOXO1 phosphorylation or POMC expression after ICV insulin administration. These findings suggest that hypothalamic AKT responds to insulin in broiler chicks, but FOXO1-mediated regulation of POMC expression is not induced by insulin, which may be one of the causes of excessive food intake in broiler chickens.