scholarly journals NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake

2007 ◽  
Vol 292 (4) ◽  
pp. R1728-R1737 ◽  
Author(s):  
Erin Keen-Rhinehart ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Free Food ◽  
Receptor Activation ◽  
Food Delivery ◽  
Behavioral Changes ◽  
Running Wheel ◽  
Food Hoarding ◽  
Y1 Receptor ◽  
Siberian Hamsters

Fasting triggers a constellation of physiological and behavioral changes, including increases in peripherally produced ghrelin and centrally produced hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most species; however, hamsters primarily increase foraging and food hoarding with smaller increases in food intake. Fasting-induced increases in foraging and food hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY, and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and subsequently NPY synthesis/release, it may be that fasting-induced increased hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging, food hoarding, and food intake? This was accomplished by injecting the NPY Y1 receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or given peripheral ghrelin injections and housed in a running wheel-based food delivery foraging system coupled with simulated-burrow housing. Three foraging conditions were used: 1) no running wheel access, free food, 2) running wheel access, free food, or 3) foraging requirement (10 revolutions/pellet) for food. Fasting was a more potent stimulator of foraging and food hoarding than ghrelin. Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced increased foraging and food intake and attenuated, but did not always completely block, fasting- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the NPY Y1 receptor is important for the effects of ghrelin- and fasting-induced increases in foraging and food intake, but other NPY receptors and/or other neurochemical systems are involved in increases in food hoarding.

Role of NPY and its receptor subtypes in foraging, food hoarding, and food intake by Siberian hamsters

2005 ◽  
Vol 289 (1) ◽  
pp. R29-R36 ◽  
Author(s):  
Diane E. Day ◽  
Erin Keen-Rhinehart ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Wheel Running ◽  
Free Food ◽  
Food Delivery ◽  
Ingestive Behavior ◽  
Receptor Subtypes ◽  
Running Wheel ◽  
Food Hoarding ◽  
Siberian Hamsters ◽  
Ingestive Behaviors

Fasting has widespread physiological and behavioral effects such as increases in arcuate nucleus neuropeptide Y (NPY) gene expression in rodents, including Siberian hamsters. Fasting also stimulates foraging and food hoarding (appetitive ingestive behaviors) by Siberian hamsters but does relatively little to change food intake (consummatory ingestive behavior). Therefore, we tested the effects of third ventricular NPY Y1 ([Pro34]NPY) or Y5 ([d-Trp34]NPY) receptor agonists on these ingestive behaviors using a wheel running-based food delivery system coupled with simulated burrow housing. Siberian hamsters had 1) no running wheel access and free food, 2) running wheel access and free food, or 3) foraging requirements (10 or 50 revolutions/pellet). NPY (1.76 nmol) stimulated food intake only during the first 4 h postinjection (∼200–1,000%) and mostly in hamsters with a foraging requirement. The Y1 receptor agonist markedly increased food hoarding (250–1,000%), increased foraging as well as wheel running per se, and had relatively little effect on food intake (<250%). Unlike NPY, the Y5 agonist significantly increased food intake, especially in foraging animals (∼225–800%), marginally increased food hoarding (250–500%), and stimulated foraging and wheel running 4–24 h postinjection, with the distribution of earned pellets favoring eating versus hoarding across time. Across treatments, food hoarding predominated early postinjection, whereas food intake tended to do so later. Collectively, NPY stimulated both appetitive and consummatory ingestive behaviors in Siberian hamsters involving Y1/Y5 receptors, with food hoarding and foraging/wheel running (appetitive) more involved with Y1 receptors and food intake (consummatory) with Y5 receptors.

Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters

2005 ◽  
Vol 288 (3) ◽  
pp. R716-R722 ◽  
Author(s):  
Erin Keen-Rhinehart ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Wheel Running ◽  
Plasma Concentrations ◽  
Free Food ◽  
Ingestive Behavior ◽  
Running Wheel ◽  
Food Hoarding ◽  
Siberian Hamsters ◽  
Wheel Running Activity ◽  
Appetitive Behaviors

Fasting triggers many effects, including increases in circulating concentrations of ghrelin, a primarily stomach-derived orexigenic hormone. Exogenous ghrelin treatment stimulates food intake, implicating it in fasting-induced increases in feeding, a consummatory ingestive behavior. In Siberian hamsters, fasting also stimulates appetitive ingestive behaviors such as foraging and food hoarding. Therefore, we tested whether systemic ghrelin injections (3, 30, and 200 mg/kg) would stimulate these appetitive behaviors using a running wheel-based food delivery system coupled with simulated burrow housing. We also measured active ghrelin plasma concentrations after exogenous ghrelin treatment and compared them to those associated with fasting. Hamsters had the following: 1) no running wheel access, free food; 2) running wheel access, free food; or 3) foraging requirement (10 revolutions/pellet), no free food. Ghrelin stimulated foraging at 0–1, 2–4, and 4–24 h postinjection but failed to affect wheel running activity not coupled to food. Ghrelin stimulated food intake initially (200–350%, first 4 h) across all groups; however, in hamsters with a foraging requirement, ghrelin also stimulated food intake 4–24 h postinjection (200–250%). Ghrelin stimulated food hoarding 2–72 h postinjection (100–300%), most markedly 2–4 h postinjection in animals lacking a foraging requirement (635%). Fasting increased plasma active ghrelin concentrations in a time-dependent fashion, with the 3- and 30-mg/kg dose creating concentrations of the peptide comparable to those induced by 24–48 h of fasting. Collectively, these data suggest that exogenous ghrelin, similar to fasting, increases appetitive behaviors (foraging, hoarding) by Siberian hamsters, but dissimilar to fasting in this species, stimulates food intake.

scholarly journals Leptin inhibits food-deprivation-induced increases in food intake and food hoarding

2008 ◽  
Vol 295 (6) ◽  
pp. R1737-R1746 ◽  
Author(s):  
Erin Keen-Rhinehart ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Food Deprivation ◽  
Food Delivery ◽  
Control Group ◽  
Sedentary Control ◽  
Food Hoarding ◽  
Siberian Hamsters ◽  
Ingestive Behaviors ◽  
Plasma Leptin ◽  
The Brain

Food deprivation stimulates foraging and hoarding and to a much lesser extent, food intake in Siberian hamsters. Leptin, the anorexigenic hormone secreted primarily from adipocytes, may act in the periphery, the brain, or both to inhibit these ingestive behaviors. Therefore, we tested whether leptin given either intracerebroventricularly or intraperitoneally, would block food deprivation-induced increases in food hoarding, foraging, and intake in animals with differing foraging requirements. Hamsters were trained in a running wheel-based food delivery foraging system coupled with simulated burrow housing. We determined the effects of food deprivation and several peripheral doses of leptin on plasma leptin concentrations. Hamsters were then food deprived for 48 h and given leptin (0, 10, 40, or 80 μg ip), and additional hamsters were food deprived for 48 h and given leptin (0, 1.25, 2.5, or 5.0 μg icv). Foraging, food intake, and hoarding were measured postinjection. Food deprivation stimulated food hoarding to a greater degree and duration than food intake. In animals with a foraging requirement, intracerebroventricular leptin almost completely blocked food deprivation-induced increased food hoarding and intake, but increased foraging. Peripheral leptin treatment was most effective in a sedentary control group, completely inhibiting food deprivation-induced increased food hoarding and intake at the two highest doses, and did not affect foraging at any dose. Thus, the ability of leptin to inhibit food deprivation-induced increases in ingestive behaviors differs based on foraging effort (energy expenditure) and the route of administration of leptin administration.

NPY Y1 receptor antagonist prevents NPY-induced torporlike hypothermia in cold-acclimated Siberian hamsters

2008 ◽  
Vol 294 (1) ◽  
pp. R236-R245 ◽  
Author(s):  
John Dark ◽  
Kimberly M. Pelz
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Phodopus Sungorus ◽  
Food Ingestion ◽  
Research Groups ◽  
Ambient Temperatures ◽  
Y1 Receptor ◽  
Siberian Hamsters ◽  
Intracerebroventricular Injections

Siberian hamsters ( Phodopus sungorus) undergo bouts of daily torpor during which body temperature decreases by as much as 20°C and provides a significant savings in energy expenditure. Natural torpor in this species is normally triggered by winterlike photoperiods and low ambient temperatures. Intracerebroventricular injection of neuropeptide Y (NPY) reliably induces torporlike hypothermia that resembles natural torpor. NPY-induced torporlike hypothermia is also produced by intracerebroventricular injections of an NPY Y1 receptor agonist but not by injections of an NPY Y5 receptor agonist. In this research, groups of cold-acclimated Siberian hamsters were either coinjected with a Y1 receptor antagonist (1229U91) and NPY or were coinjected with a Y5 receptor antagonist ( CGP71683 ) and NPY in counterbalanced designs. Paired vehicle + NPY induced torporlike hypothermia in 92% of the hamsters, whereas coinjection of Y1 antagonist + NPY induced torporlike hypothermia in 4% of the hamsters. In contrast, paired injections of vehicle + NPY and Y5 antagonist + NPY induced torporlike hypothermia in 100% and 91% of the hamsters, respectively. Although Y5 antagonist treatment alone had no effect on body temperature, Y1 antagonist injections produced hyperthermia compared with controls. Both Y1 antagonist and Y5 antagonist injections significantly reduced food ingestion 24 h after treatment. We conclude that activation of NPY 1 receptors is both sufficient and necessary for NPY-induced torporlike hypothermia.

scholarly journals Reduced Ghrelin Secretion in the Hypothalamus of Rats due to Cisplatin-Induced Anorexia

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3773-3782 ◽  
Author(s):  
Koji Yakabi ◽  
Chiharu Sadakane ◽  
Masamichi Noguchi ◽  
Shino Ohno ◽  
Shoki Ro ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Receptor Activation ◽  
Serotonin 2C Receptor ◽  
Receptor Mrna ◽  
Gastrointestinal Side Effects ◽  
Ghrelin Secretion ◽  
Fasted Rats

Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients’ quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

scholarly journals CCK-Induced Reduction of Food Intake and Hindbrain MAPK Signaling Are Mediated by NMDA Receptor Activation

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2633-2646 ◽  
Author(s):  
Carlos A. Campos ◽  
Jason S. Wright ◽  
Krzysztof Czaja ◽  
Robert C. Ritter
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Vagal Afferents ◽  
Mapk Kinase ◽  
Vagal Afferent

The dorsal vagal complex of the hindbrain, including the nucleus of the solitary tract (NTS), receives neural and humoral afferents that contribute to the process of satiation. The gut peptide, cholecystokinin (CCK), promotes satiation by activating gastrointestinal vagal afferents that synapse in the NTS. Previously, we demonstrated that hindbrain administration of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists attenuate reduction of food intake after ip CCK-8 injection, indicating that these receptors play a necessary role in control of food intake by CCK. However, the signaling pathways through which hindbrain NMDA receptors contribute to CCK-induced reduction of food intake have not been investigated. Here we report CCK increases phospho-ERK1/2 in NTS neurons and in identified vagal afferent endings in the NTS. CCK-evoked phospho-ERK1/2 in the NTS was attenuated in rats pretreated with capsaicin and was abolished by systemic injection of a CCK1 receptor antagonist, indicating that phosphorylation of ERK1/2 occurs in and is mediated by gastrointestinal vagal afferents. Fourth ventricle injection of a competitive NMDA receptor antagonist, prevented CCK-induced phosphorylation of ERK1/2 in hindbrain neurons and in vagal afferent endings, as did direct inhibition of MAPK kinase. Finally, fourth ventricle administration of either a MAPK kinase inhibitor or NMDA receptor antagonist prevented the reduction of food intake by CCK. We conclude that activation of NMDA receptors in the hindbrain is necessary for CCK-induced ERK1/2 phosphorylation in the NTS and consequent reduction of food intake.

scholarly journals Third ventricular coinjection of subthreshold doses of NPY and AgRP stimulate food hoarding and intake and neural activation

2012 ◽  
Vol 302 (1) ◽  
pp. R37-R48 ◽  
Author(s):  
Brett J. W. Teubner ◽  
Erin Keen-Rhinehart ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Zona Incerta ◽  
Central Nucleus ◽  
Behavioral Experiment ◽  
Neural Activation ◽  
Food Hoarding ◽  
Siberian Hamsters ◽  
Hypothalamic Nuclei ◽  
Ingestive Behaviors ◽  
Agouti Related Protein

We previously demonstrated that 3rd ventricular (3V) neuropeptide Y (NPY) or agouti-related protein (AgRP) injection potently stimulates food foraging/hoarding/intake in Siberian hamsters. Because NPY and AgRP are highly colocalized in arcuate nucleus neurons in this and other species, we tested whether subthreshold doses of NPY and AgRP coinjected into the 3V stimulates food foraging, hoarding, and intake, and/or neural activation [c-Fos immunoreactivity (c-Fos-ir)] in hamsters housed in a foraging/hoarding apparatus. In the behavioral experiment, each hamster received four 3V treatments by using subthreshold doses of NPY and AgRP for all behaviors: 1) NPY, 2) AgRP, 3) NPY+AgRP, and 4) saline with a 7-day washout period between treatments. Food foraging, intake, and hoarding were measured 1, 2, 4, and 24 h and 2 and 3 days postinjection. Only when NPY and AgRP were coinjected was food intake and hoarding increased. After identical treatment in separate animals, c-Fos-ir was assessed at 90 min and 14 h postinjection, times when food intake (0–1 h) and hoarding (4–24 h) were uniquely stimulated. c-Fos-ir was increased in several hypothalamic nuclei previously shown to be involved in ingestive behaviors and the central nucleus of the amygdala (CeA), but only in NPY+AgRP-treated animals (90 min and 14 h: magno- and parvocellular regions of the hypothalamic paraventricular nucleus and perifornical area; 14 h only: CeA and sub-zona incerta). These results suggest that NPY and AgRP interact to stimulate food hoarding and intake at distinct times, perhaps released as a cocktail naturally with food deprivation to stimulate these behaviors.

ICV NPY Y1 receptor agonist but not Y5 agonist induces torpor-like hypothermia in cold-acclimated Siberian hamsters

2007 ◽  
Vol 292 (6) ◽  
pp. R2299-R2311 ◽  
Author(s):  
Kimberly M. Pelz ◽  
John Dark
Keyword(s):  
Receptor Activation ◽  
Neural Mechanisms ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Y1 Receptor ◽  
Siberian Hamsters ◽  
Npy Receptor ◽  
Intracerebroventricular Injections ◽  
Metabolic Expenditure ◽  
Compare And Contrast

The reduced metabolism derived from daily torpor enables numerous small mammals, including Siberian hamsters, to survive periods of energetic challenge. Little is known of the neural mechanisms underlying the initiation and expression of torpor. Hypothalamic neuropeptide Y (NPY) contributes to surviving energetic challenges by both increasing food ingestion and reducing metabolic expenditure. Intracerebroventricular injections of NPY in cold-acclimated Siberian hamsters induce torpor-like hypothermia comparable to natural torpor. Multiple NPY receptor subtypes have been identified, and the Y1 receptor and Y5 receptor both contribute to the orexigenic effect of NPY. The purpose of this research was to compare and contrast the effects of Y1 receptor activation by a specific Y1 agonist ([d-Arg25]-NPY) or Y5 receptor activation by a specific Y5 agonist ([d-Trp34]-NPY) on body temperature and subsequent food intake in cold-acclimated Siberian hamsters. Intracerebroventricular injections of Y1 agonist produced torporlike hypothermia closely resembling that induced by intracerebroventricular NPY. The intracerebroventricular Y5 agonist infrequently produced hypothermia reaching criterion for torpor and that failed to resemble either NPY-induced or natural torpor. Combined injections of Y1 and Y5 agonists resulted in hypothermia comparable to Y5 agonist treatments alone, negating the mimicry of NPY treatment seen with Y1 agonist alone. Prior treatment with Y1 agonist or Y5 agonist surprisingly had lingering effects on NPY-induced torpor expression, Y1 agonist enhanced and Y5 agonist inhibited the effect of NPY. The ability of NPY to induce torporlike hypothermia, especially its initiation, most likely involves activation of the NPY Y1 receptor subtype.

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