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

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.     

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

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 ([Pro(34)]NPY) or Y5 ([D-Trp(34)]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 ( approximately 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 ( approximately 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.     

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

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.     

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

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 microg ip), and additional hamsters were food deprived for 48 h and given leptin (0, 1.25, 2.5, or 5.0 microg 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.     

MTII attenuates ghrelin- and food deprivation-induced increases in food hoarding and food intake

Food deprivation triggers a constellation of physiological and behavioral changes including increases in peripherally-produced ghrelin and centrally-produced agouti-related protein (AgRP). Upon refeeding, food intake is increased in most species, however hamsters primarily increase food hoarding. Food deprivation-induced increases in food hoarding by Siberian hamsters are mimicked by peripheral ghrelin and central AgRP injections. Because food deprivation stimulates ghrelin as well as AgRP synthesis/release, food deprivation-induced increases in hoarding may be mediated by melanocortin 3 or 4 receptor (MC3/4-R) antagonism via AgRP, the MC3/4-R inverse agonist. Therefore, we asked: Can a MC3/4-R agonist block food deprivation- or ghrelin-induced increases in foraging, food hoarding and food intake? This was accomplished by injecting melanotan II (MTII), a synthetic MC3/4-R agonist, into the 3rd ventricle in food deprived, fed or peripheral ghrelin injected hamsters and housed in a running wheel-based food delivery foraging system. Three foraging conditions were used: a) no running wheel access, non-contingent food, b) running wheel access, non-contingent food or c) a foraging requirement for food (10 revolutions/pellet). Food deprivation was a more potent stimulator of foraging and hoarding than ghrelin. Concurrent injections of MTII completely blocked food deprivation- and ghrelin-induced increases in food intake and attenuated, but did not always completely block, food deprivation- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the MC3/4-R are involved in ghrelin- and food deprivation-induced increases in food intake, but other neurochemical systems, such as previously demonstrated with neuropeptide Y, also are involved in increases in food hoarding as well as foraging.     

MTII attenuates ghrelin- and food deprivation-induced increases in food hoarding and food intake

Food deprivation triggers a constellation of physiological and behavioral changes including increases in peripherally-produced ghrelin and centrally-produced agouti-related protein (AgRP). Upon refeeding, food intake is increased in most species, however hamsters primarily increase food hoarding. Food deprivation-induced increases in food hoarding by Siberian hamsters are mimicked by peripheral ghrelin and central AgRP injections. Because food deprivation stimulates ghrelin as well as AgRP synthesis/release, food deprivation-induced increases in hoarding may be mediated by melanocortin 3 or 4 receptor (MC3/4-R) antagonism via AgRP, the MC3/4-R inverse agonist. Therefore, we asked: Can a MC3/4-R agonist block food deprivation- or ghrelin-induced increases in foraging, food hoarding and food intake? This was accomplished by injecting melanotan II (MTII), a synthetic MC3/4-R agonist, into the 3rd ventricle in food deprived, fed or peripheral ghrelin injected hamsters and housed in a running wheel-based food delivery foraging system. Three foraging conditions were used: a) no running wheel access, non-contingent food, b) running wheel access, non-contingent food or c) a foraging requirement for food (10 revolutions/pellet). Food deprivation was a more potent stimulator of foraging and hoarding than ghrelin. Concurrent injections of MTII completely blocked food deprivation- and ghrelin-induced increases in food intake and attenuated, but did not always completely block, food deprivation- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the MC3/4-R are involved in ghrelin- and food deprivation-induced increases in food intake, but other neurochemical systems, such as previously demonstrated with neuropeptide Y, also are involved in increases in food hoarding as well as foraging.     

Mu-opioid receptors and dietary protein stimulate a gut-brain neural circuitry limiting food intake

Intestinal gluconeogenesis is involved in the control of food intake. We show that mu-opioid receptors (MORs) present in nerves in the portal vein walls respond to peptides to regulate a gut-brain neural circuit that controls intestinal gluconeogenesis and satiety. In vitro, peptides and protein digests behave as MOR antagonists in competition experiments. In vivo, they stimulate MOR-dependent induction of intestinal gluconeogenesis via activation of brain areas receiving inputs from gastrointestinal ascending nerves. MOR-knockout mice do not carry out intestinal gluconeogenesis in response to peptides and are insensitive to the satiety effect induced by protein-enriched diets. Portal infusions of MOR modulators have no effect on food intake in mice deficient for intestinal gluconeogenesis. Thus, the regulation of portal MORs by peptides triggering signals to and from the brain to induce intestinal gluconeogenesis are links in the satiety phenomenon associated with alimentary protein assimilation.     

Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance

Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the failure to upregulate AgRP in response to starvation, and constitutive increases in hypothalamic levels of pro-opiomelanocortin and its cleavage product α-melanocyte-stimulating hormone that typically contribute to a lean phenotype. We propose a conceptual framework for considering how autophagy-regulated lipid metabolism within hypothalamic neurons may modulate neuropeptide levels to have immediate effects on food intake, as well as long-term effects on energy homeostasis. Regulation of hypothalamic autophagy could become an effective intervention in conditions such as obesity and the metabolic syndrome.     

Fat pad-specific effects of lipectomy on foraging, food hoarding, and food intake

Unlike most species, after food deprivation, Siberian hamsters increase foraging and food hoarding, two appetitive ingestive behaviors, but not food intake, a consummatory ingestive behavior. We previously demonstrated (Wood AD, Bartness TJ, Am J Physiol Regul Integr Comp Physiol 272: R783-R792, 1997) that increases in food hoarding are triggered by directly decreasing body fat levels through partial surgical lipectomy; however, we did not test if lipectomy affected foraging, nor if the magnitude of the lipid deficit affected food hoard size. Therefore, we tested whether varying the size of the lipectomy-induced lipid deficit and/or foraging effort affected foraging, food hoarding, or food intake. This was accomplished by housing adult male Siberian hamsters in a foraging/hoarding system and removing (x) both epididymal white adipose tissue (EWATx) pads, both inguinal white adipose tissue (IWATx) pads, or both EWAT and IWAT pads (EWATx + IWATx) and measuring foraging, food hoarding, and food intake for 12 wk. The lipectomy-induced lipid deficit triggered different patterns of white adipose tissue mass compensation that varied with foraging effort. Foraging for food (10 wheel revolutions to earn a food pellet) abolished the EWATx-induced compensation in IWAT pad mass. The magnitude of the lipid deficit did not engender a proportional change in any of the appetitive or consummatory ingestive behaviors. EWATx caused the greatest increase in food hoarding compared with IWATx or EWATx + IWATx, when animals were required to forage for their food. Collectively, it appears that the magnitude of a lipid deficit does not affect appetitive or consummatory behaviors; rather, when energy (foraging) demands are increased, loss of specific (gonadal) fat pads can preferentially stimulate increases in food hoarding.     

Hypothalamic AMPK-induced autophagy increases food intake by regulating NPY and POMC expression

Hypothalamic AMP-activated protein kinase (AMPK) plays important roles in the regulation of food intake by altering the expression of orexigenic or anorexigenic neuropeptides. However, little is known about the mechanisms of this regulation. Here, we report that hypothalamic AMPK modulates the expression of NPY (neuropeptide Y), an orexigenic neuropeptide, and POMC (pro-opiomelanocortin-α), an anorexigenic neuropeptide, by regulating autophagic activity in vitro and in vivo. In hypothalamic cell lines subjected to low glucose availability such as 2-deoxy-d-glucose (2DG)-induced glucoprivation or glucose deprivation, autophagy was induced via the activation of AMPK, which regulates ULK1 and MTOR complex 1 followed by increased Npy and decreased Pomc expression. Pharmacological or genetic inhibition of autophagy diminished the effect of AMPK on neuropeptide expression in hypothalamic cell lines. Moreover, AMPK knockdown in the arcuate nucleus of the hypothalamus decreased autophagic activity and changed Npy and Pomc expression, leading to a reduction in food intake and body weight. AMPK knockdown abolished the orexigenic effects of intraperitoneal 2DG injection by decreasing autophagy and changing Npy and Pomc expression in mice fed a high-fat diet. We suggest that the induction of autophagy is a possible mechanism of AMPK-mediated regulation of neuropeptide expression and control of feeding in response to low glucose availability.     

Differential opiate influences on food hoarding and intake in the deer mouse, Peromyscus maniculatus

The feeding behavior of the deer mouse, Peromyscus maniculatus, includes food hoarding as well as ingestion. In this animal the mu opiate agonist, morphine, and the kappa opiate agonist, U-50, 488H, selectively stimulate food hoarding and ingestion, respectively. This suggests that mu and kappa opiate systems may differentially mediate primary components of natural feeding behavior.     

PYY(3-36) into the arcuate nucleus inhibits food deprivation-induced increases in food hoarding and intake

Central administration of neuropeptide Y (NPY) increases food intake in laboratory rats and mice, as well as food foraging and hoarding in Siberian hamsters. The NPY-Y1 and Y5 receptors (Rs) within the hypothalamus appear sufficient to account for these increases in ingestive behaviors. Stimulation of NPY-Y2Rs in the Arcuate nucleus (Arc) has an anorexigenic effect as shown by central or peripheral administration of its natural ligand peptide YY (3-36) and pharmacological NPY-Y2R antagonism by BIIE0246 increases food intake. Both effects on food intake by NPY-Y2R agonism and antagonism are relatively short-lived lasting ∼4 h. The role of NPY-Y2Rs in appetitive ingestive behaviors (food foraging/hoarding) is untested, however. Therefore, Siberians hamsters, a natural food hoarder, were housed in a semi-natural burrow/foraging system that had (a) foraging requirement (10 revolutions/pellet), no free food (true foraging group), (b) no running wheel access, free food (general malaise control) or (c) running wheel access, free food (exercise control). We microinjected BIIE0246 (antagonist) and PYY_(3-36) (agonist) into the Arc to test the role of NPY-Y2Rs there on ingestive behaviors. Food foraging, hoarding, and intake were not affected by Arc BIIE0246 microinjection in fed hamsters 1, 2, 4, and 24 h post injection. Stimulation of NPY-Y2Rs by PYY_(3-36) inhibited food intake at 0–1 and 1–2 h and food hoarding at 1–2 h without causing general malaise or affecting foraging. Collectively, these results implicate a sufficiency, but not necessity, of the Arc NPY-Y2R in the inhibition of food intake and food hoarding by Siberian hamsters.     

Androgens stimulate specific aspects of maternal nest-building and reduce food intake in rabbits

Fluctuations in the plasma concentration of estradiol, progesterone, and prolactin across pregnancy regulate maternal nest-building (digging, straw-carrying, and hair-plucking) and food intake in rabbits. Because testosterone levels also change through pregnancy, we investigated if the injection of testosterone propionate (TP; 1 or 5 mg/day) or 5alpha-dihydrotestosterone propionate (5 or 10 mg/day) for 20 days, alone and combined with progesterone (P; 10 mg/day from days 2 to 15), modulated nest-building and food intake in ovariectomized rabbits. Only the combined injection of TP (5 mg/day) plus P stimulated digging and no treatment promoted straw-carrying or hair-plucking. Both androgens induced hair-loosening from the ventrum, an effect counteracted by P. High doses of TP and 5alpha-dihydrotestosterone propionate reduced food intake by 60-70% of baseline values; this effect was counteracted by P in TP-treated animals. These results support a participation of androgens in specific aspects of maternal nest-building and reveal a strong inhibitory effect on food intake.     

Neural and hormonal control of food hoarding

Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity.     

Leptin-derived peptides that stimulate food intake and increase body weight following peripheral administration

We previously showed that peptides containing leptin sequences 1-33 or 61-90 are taken up by the rat brain. We now report the effects of these peptides on food intake and body weight in mature rats. Peptides were infused intravenously for 4weeks, using Alzet minipumps. Dosages were 20μg/kg/day in experiment I, and 60μg/kg/day in experiment 2. In experiment 1, female rats receiving peptides 1-33 and 61-90 each underwent an approximate doubling of the weight gain of control rats. These peptides also increased food intake in female rats. Peptide 15-32, which has a lesser degree of brain uptake, gave a smaller weight gain. Peptide 83-108, which is not taken up by the brain, had no effect on weight gain or food intake. Similar results were obtained in experiment 2. In male rats, however, none of the peptides caused significant changes in food intake or body weight. This was at least partly due to the fact that all male rats underwent vigorous weight increases. We conclude that peptides 1-33 and 61-90 acted as leptin antagonists, stimulating food intake and body weight increases, at least in female rats. These peptides may lead to clinical applications in conditions such as anorexia and cachexia.     

Effect of food intake on left ventricular wall stress

Objective

Left ventricular wall stress has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether left ventricular wall stress is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. Meridional end-systolic wall stress (ESS) and circumferential end-systolic wall stress (cESS) were measured before, 30 minutes after, and 110 minutes after a standardised meal.

Results

Both ESS and cESS decreased significantly (P?<?0.001) from fasting values 30 minutes after the meal, and had not returned to baseline after 110 minutes. ESS decreased from 65?±?16 kdynes/cm² (fasting) to 44?±?12 kdynes/cm² 30 minutes after, and to 58?±?13 kdynes/cm² 110 minutes after eating. cESS decreased from 98?±?24 kdynes/cm² to 67?±?18 kdynes/cm² 30 minutes after, and to 87?±?19 kdynes/cm² 110 minutes after the meal.

Conclusion

This study shows that left ventricular wall stress is affected by food intake in healthy subjects.     

Hypoglycaemia and food intake in rats given graduated doses of insulin.

Hypoglycaemia of varying duration was induced with graduated doses of long-acting insulin (10, 40 and 160 U/kg b.w.) in young, growing (8- to 10-week-old) male Wistar rats fed ad libitum on two different diets. In all, 6 doses of insulin were administered, at 48-hour intervals. The blood glucose level and food consumption were determined 3, 6, 12, 24 and 48 hours after injecting the insulin. Both the hypoglycaemic effect and elevated food intake during hypoglycaemia depended on the dose of insulin and not on the type of diet. Total food consumption during the experiment (12 days) was markedly raised only in the groups given the maximum dose of insulin (160 U/kg b.w.). The weight gain in all the experimental groups was lower than in the control groups and food consumption per weight gain unit was higher.     

Rutecarpine ameliorates bodyweight gain through the inhibition of orexigenic neuropeptides NPY and AgRP in mice

Orexigenic neuropeptides NPY and AgRP play major roles in feeding and are closely related to obesity and diabetic metabolic syndrome. This study explored the inhibitory effect of rutecarpine on feeding and obesity in high-fat-diet-induced (C57BL/6) and leptin-deficient (ob/ob) obese mice. Both mice strains developed obesity, but the obesity was inhibited by the reduced food intake resulting from rutecarpine treatment (0.01%, p < 0.01). Blood cholesterol, non-fasting glucose, insulin, and leptin levels were reduced, compared with the control group. Rutecarpine inhibited the expression of NPY and AgRP in the arcuate nucleus (ARC) of the hypothalamus and suppressed the expression of both neuropeptides in N29-4 neuronal cells. These results indicate that rutecarpine ameliorates obesity by inhibiting food intake, which involves inhibited expression of the orexigenic neuropeptides NPY and AgRP.     

Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

Obesity is an escalating epidemic, but an effective non-invasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated by their peptide character. In order to overcome this unfavorable fact, we have applied the lipidization of neuropeptide prolactin-releasing peptide (PrRP), whose strong anorexigenic effect was demonstrated. A palmitoylated analog of human PrRP (h palm-PrRP31) was injected in free-fed Wistar rats by three routes: subcutaneous (s.c.), intraperitoneal (i.p) (both 5 mg/kg) and intravenous (i.v.) (from 0.01 to 0.5 mg/kg). We found a circulating compound in the blood after all three applications with the highest concentration after i.v. administration. This corresponds to the effect on food intake, which was also strongest after i.v. injection. Moreover, this is in agreement with the fact that the expression of c-Fos in specific brain regions involved in food intake regulation was also highest after intravenous application. Pharmacokinetic data are further supported by results obtained from dynamic light scattering and CD spectroscopy. Human palm-PrRP31 analog showed a strong tendency to micellize, and formation of aggregates suggested lower availability after i.p. or s.c. application. We have demonstrated that palm-PrRP influenced food intake even in free fed rats. Not surprisingly, the maximal effect was achieved after the intravenous application even though two orders of magnitude lower dose was used compared to both two other applications. We believe that palm-PrRP could have a potential as an antiobesity drug when its s.c. application would be improved.     

Increased feeding and food hoarding following food deprivation are associated with activation of dopamine and orexin neurons in male Brandt's voles

Small mammals usually face energetic challenges, such as food shortage, in the field. They have thus evolved species-specific adaptive strategies for survival and reproductive success. In the present study, we examined male Brandt's voles (Lasiopodomys brandtii) for their physiological, behavioral, and neuronal responses to food deprivation (FD) and subsequent re-feeding. Although 48 hr FD induced a decrease in body weight and the resting metabolic rate (RMR), such decreases did not reach statistical significance when compared to the control males that did not experience FD. During the first 2 hr of re-feeding following 48 hr FD, voles showed higher levels of feeding than controls. However, when permitted to hoard food, FD voles showed an increase in food hoarding, rather than feeding, compared to the controls. Further, both feeding and food hoarding induced an increase in neuronal activation, measured by Fos-ir, in a large number of brain areas examined. Interestingly, feeding and food hoarding also induced an increase in the percentage of tyrosine hydroxylase immunoreactive (TH-ir) cells that co-expressed Fos-ir in the ventral tegmental area (VTA), whereas both FD and feeding induced an increase in the percentage of orexin-ir cells that co-expressed Fos-ir in the lateral hypothalamus (LH). Food hoarding also increased orexin-ir/Fos-ir labeling in the LH. Together, our data indicate that food-deprived male Brandt's voles display enhanced feeding or food hoarding dependent upon an environmental setting. In addition, changes in central dopamine and orexin activities in selected brain areas are associated with feeding and hoarding behaviors following FD and subsequent re-feeding.