Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice

Abstract

Swart, I., J. W. Jahng, J. M. Overton, and T. A. Houpt. Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice. Am J Physiol Regul Integr Comp Physiol 283: R1020-R1026, 2002 10.1152/ajpregu.00501.2001 increases hypothalamic neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels and decreases proopiomelanocortin (POMC) mRNA levels; refeeding restores these levels. We determined the time course of changes in hypothalamic NPY, AGRP, and POMC mRNA levels on refeeding after 24 h FD in C57BL mice by in situ hybridization. After 24 h deprivation, mice were refed with either chow or a palatable mash containing no calories or were injected with murine leptin (100 g) without food. Mice were perfused 2 or 6 h after treatment. Food deprivation increased hypothalamic NPY mRNA (108 Ϯ 6%) and AGRP mRNA (78 Ϯ 7%) and decreased hypothalamic POMC mRNA (Ϫ15 Ϯ 1%). Refeeding for 6 h, but not 2 h, was sufficient to reduce (but not restore) NPY mRNA, did not affect AGRP mRNA, and restored POMC mRNA levels to ad libitum control levels. Intake of the noncaloric mash had no effect on mRNA levels, and leptin administration after deprivation (at a dose sufficient to reduce refeeding in FD mice) was not sufficient to affect mRNA levels. These results suggest that gradual postabsorptive events subsequent to refeeding are required for the restoration of peptide mRNA to baseline levels after food deprivation in mice. palatable; preabsorptive; postabsorptive; time course; arcuate nucleus; in situ hybridization; neuropeptide Y; agoutirelated protein; proopiomelanocortin CALORIC DEPRIVATION INVOKES a complex array of hormonal, neural, and metabolic responses to reduce energy expenditure to defend body weight. Associated with reduced caloric availability is an increased drive to eat. Both the reduced energy expenditure and increased appetite associated with reduced energy availability may be regulated by a network of hypothalamic neuropeptides (30,52,61). Agouti-related protein (AGRP), a melanocortin receptor antagonist, is coexpressed with neuropeptide Y (NPY) in most hypothalamic NPYergic arcuate nucleus neurons (8), and hypothalamic peptide content and mRNA levels of both NPY (7, 21, 31) and AGRP (33, 42) are increased by food deprivation. Proopiomelanocortin (POMC) is expressed in a separate population of arcuate nucleus neurons and via ␣-melanocyte stimulating hormone (␣-MSH), a posttranslational product of POMC and a melanocortin receptor agonist, tonically inhibits food intake (5, 34), whereas food deprivation results in decreased POMC mRNA levels in the arcuate nucleus (42). Therefore, during conditions of altered energy balance, NPY and AGRP signaling via NPY-Y1/Y5 and melanocortin MC-4 receptors, respectively, and POMC/ ␣-MSH signaling also via MC-4 receptors are coordinately regulated to defend body weight and stimulate appetite, thus maintaining energy homeostasis.Little is known about the time course of the restoration of food deprivation-induced changes in hypothalamic peptide mRNA levels on ref...

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.…”

Ghrelin and lipid metabolism: key partners in energy balance

“…3). AMPK activation in several hypothalamic nuclei such as VMH, ARC, and PVH has a significant part in mediating counter-regulatory responses to acute hypoglycemia, such as attenuated hypoglycemia-induced increases in plasma corticosterone, glucagons, and epinephrine [ (Sanacora et al 1990, Kalra et al 1991, Schwartz et al 1997, Kristensen et al 1998, Swart et al 2002, Minokoshi et al 2004, Ló pez et al 2006 (continued)…”

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

“…mRNA expressions of NPY, proopiomelanocortin (POMC) and cocaine-amphetamine regulated transcript (CART) in the arcuate nucleus responding to food deprivation were examined together with the plasma levels of leptin and corticosterone. Circulating leptin decreases (Schwartz et al, 1995;Ahima et al, 1996;Makimura et al, 2003) and corticosterone increases (Timofeeva et al, 2002;Makimura et al, 2003;Jahng et al, 2005) during food deprivation, and these stress-responding hormones are known to be involved in the arcuate expression of feeding peptides (Tempel and Leibowitz, 1994;Ahima et al, 1996;Zakrzewska et al, 1999;Schwartz et al, 2000;Swart et al, 2002;Makimura et al, 2003).…”