Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior.

Abstract

Neuropeptide Y (NPY) was injected directly Into the paraventricular nucleus of the hypothalamus (PVN) of satiated, brain-cannulated rats, and food and water intake were measured 0.5, 1, 2, 4, and 22 hr postinjection. NPY (24, 78, 235, 783, and 2351 pmol/0.3 pl) produced a large, dosedependent increase in food intake as well as a small increase in water intake. The latency to eat was about 10 min, with substantial feeding occurring in the first 30 min. At doses below 78 pmol, the eating generally occurred only within the first hour. At doses above 235 pmol, however, the subjects' food intake continued to increase such that by 4 hr postinjection they had consumed the equivalent of normal 22-hr intake, and 22 hr postinjection they had also eaten significantly more than control subjects. Previous studies have shown that norepinephrine injected into the PVN stimulates feeding through aadrenergic receptors. To investigate a possible interaction, subjects were given PVN injections of phentolamine (60 nmol) prior to injections of either NPY (78 pmol) or norepinephrine (20 nmol). Phentolamine pretreatment significantly decreased feeding elicited by norepinephrine without affecting feeding elicited by NPY. This suggests that NPY does not stimulate feeding through the release of endogenous norepinephrine. The powerful stimulation of feeding elicited by this neuropeptide suggests an important role for hypothalamic NPY, or a structurally related peptide, in the regulation of feeding behavior.Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was discovered in porcine brain by Tatemoto et al. in 1982 (1, 2). Subsequently, the concentration of NPY in the brain was found to exceed the concentration of any other peptide (3). Our interest in a possible role for NPY in the control of feeding behavior was stimulat ed by the recent reports that it is colocalized with norepinephrine (NE) and epinephrine in brainstem catecholamine cell groups, which send afferent fibers to the paraventricular nucleus of the hypothalamus (PVN) (4, 5; however, see ref.32), and also by reports that it is found within numerous presynaptic terminals in the PVN (3, 6, 7). Experiments investigating brain mechanisms of feeding behavior have demonstrated that central injections of several putative neurotransmitters, including NE, y-aminobutyric acid, acetylcholine, and opiate agonists, can selectively stimulate feeding behavior (8-11). The most intensely studied of these is NE. It has been shown that PVN injection of exogenous NE, or drug-induced release of endogenous NE from brainstem catecholamine neurons that ascend to the PVN, elicits feeding behavior through stimulation of a2-adrenergic receptors (12-15). The feeding response appears to be mediated through the PVN, since this is the brain region that is most sensitive to NE and since NE-induced feeding is severely attenuated by PVN lesions (12, 16). A role for this system in natural (deprivation-induced) feeding was suggested by the findings that PVN a-adrenergic r...

Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea‐pig

“…When NPY is injected intracerebroventricularly (i.c.v. ) or directly into the hypothalamus, feeding is markedly increased (Haynes et al, 1998;Stanley & Leibowitz, 1985). This stimulatory e ect has been reported not only in rodents (Iyengar et al, 1999;Levine & Morley, 1984;Morley et al, 1987a, b), but also in virtually all vertebrates that have been studied (Boswell et al, 1993;Kuenzel et al, 1987;Kulkoskyfeeding.…”

Sustained hyperphagia in adolescent rats that experienced neonatal maternal separation

“…Further studies are required to determine whether NH pups show lower metabolic rate than MS pups per se after repeated weight cycles. NPY potently stimulates food intake, [15][16][17] food deprivation increases the hypothalamic mRNA expression and release of NPY, 31,[36][37][38] and increased expression of the hypothalamic NPY appears to be implicated in the induction of hyperphagia. 39,40 These reports support the idea that increased expression of NPY in the arcuate nucleus of NH/RF pups responding to the first fasting trial on PND 29 might have contributed, at least partly, to the compensatory hyperphagia on PND 30.…”

“…13,14 NPY, a potent orexic peptide, stimulates feeding. [15][16][17] Several results suggest that glucocorticoids regulate the hypothalamic NPY expression: adrenalectomy downregulates the expression of NPY gene in the hypothalamus; 18 NPY neurons in the hypothalamic arcuate nucleus contain glucocorticoid receptors 19 and elevated plasma corticosterone appears to be necessary for fastinginduced increase in NPY mRNA expression. 20,21 These reports led us to hypothesize that neonatal MS may lead to development of eating disorders in the offspring later in life, possibly, due to altered HPA axis characteristics modulating the hypothalamic expression of feeding peptides.…”

The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation

“…Neonatal maternal separation, an animal model of stressful experiences in childhood, can permanently modify the characteristics of HPA axis in the offspring (Plotsky and Meaney, 1993;Suchecki and Tufik, 1997;van Oers et al, 1998;Liu et al, 2000). Neuropeptide Y (NPY), the most potent orexic peptide known, stimulates feeding (Stanley and Leibowitz, 1985;Kalra et al, 1999;Schwartz et al, 2000). Previous studies have reported that experiences of maternal separation during pre-weaning period (MS) increase the hypothalamic NPY level in rats later in life (Jimenez-Vasquez et al, 2001;Husum and Mathe, 2002), and that the hypothalamic NPY expression is dis-regulated in MS rats in relation with the HPA axis dysfunction Ryu et al, 2008).…”