Action of MT-II on ghrelin-induced feeding in the paraventricular nucleus of the hypothalamus

Abstract

Ghrelin is a 28 amino-acid peptide that has been shown to induce positive energy balance when administered both peripherally and centrally. This effect appears to occur by increasing food intake and by reducing fat utilization. Ghrelin injected into the PVN increases food intake dose-dependently. The NPY receptor has been implicated in the orexigenic effect of ghrelin, but until now, the role of melanocortins on the effect of ghrelin in the PVN has not been reported. Sprague-Dawley rats were stimulated to eat by PVN ghrelin. Pre-injection of 10 pmol of MT II into the PVN caused a significant decrease in ghrelin-induced feeding in both 0-1 h and 0-4 h food intake studies. This finding indicates that MC 3/4-R signaling appears to be recruited by ghrelin, in the PVN, in its role to induce feeding.

Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice

“…It stimulates food intake in rodents and man [5][6][7][8], where peak levels in plasma occur just before each meal and fall rapidly after refeeding, suggesting that it serves to initiate food consumption [9]. To enhance appetite, ghrelin acts in the hypothalamus, where it promotes neuropeptide Y (NPY) and orexin gene expression and inhibits the production of pro-opiomelanocortin/α-melanocyte stimulating hormone (-MSH) via activation of the GHS-R [10][11][12][13][14][15][16]. We recently showed that intracerebroventricular infusion of NPY hampers insulin's capacity to suppress endogenous glucose production (EGP) [17], whereas central injection of melanotan II, a synthetic analogue of α-MSH, reinforces insulin action on glucose disposal [18].…”

Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reduces energy intake

“…The PVN is a central structure in the regulation of energy metabolism, and several neuropeptides in the PVN have been reported to affect energy metabolism. Neuropeptide Y (NPY; 3,8), agouti-related peptide (13,57), and ghrelin (34,44) stimulate eating after administration into the PVN. On the other hand, elevated leptin expression in the PVN significantly reduces food intake (1).…”

Ghrelin in the CNS: From hunger to a rewarding and memorable meal?

“…However, it should be noted that the evidence for longer-term effects is weaker. In the majority of studies, single injections of ghrelin typically have not produced increases in food intake longer than a few hours (e.g., see (Gaskin et al, 2003;Gilg and Lutz, 2006;Kalra et al, 2005;Olszewski et al, 2007b;Olszewski et al, 2003a;Olszewski et al, 2003b;Shrestha et al, 2004;Shrestha et al, 2006)). …”

“…Shrestha et al performed a series of site-specific injection studies utilizing ghrelin, AgRP and MTII and concluded that ghrelin induction of feeding relies on the recruitment of AgRP -especially within the ARC-PVN pathway -as one of the obligatory mediators of its orexigenic effect (Shrestha et al, 2004;Shrestha et al, 2006). This notion is supported by the findings of Shaw et al who determined that MC3 and MC4 receptor knock-out mice increase consumption when injected with the GHS-R agonist, but the magnitude of the feeding response is much lower than in wild-type controls (Shaw et al, 2005).…”

“…Pretreatment with the Y1 and Y5 receptor antagonist reduces or completely abolishes a consummatory response to ghrelin and synthetic GHSs (Bagnasco et al, 2003;Faulconbridge et al, 2005;Lawrence et al, 2002), and so does administration of alpha-melanocyte stimulating hormone (alpha-MSH) and its synthetic analogue, melanotan II (MTII) which compete with AgRP for the same melanocortin 3/4 (MC3/4) receptors (Olszewski et al, 2007a;Shrestha et al, 2004). Shrestha et al performed a series of site-specific injection studies utilizing ghrelin, AgRP and MTII and concluded that ghrelin induction of feeding relies on the recruitment of AgRP -especially within the ARC-PVN pathway -as one of the obligatory mediators of its orexigenic effect (Shrestha et al, 2004;Shrestha et al, 2006).…”