Seasonal physiology of the wild raccoon dog (Nyctereutes procyonoides)

The raccoon dog (Nyctereutes procyonoides) is a canid omnivore with autumnal fattening and winter sleep. Farmraised raccoon dogs have elevated plasma leptin and growth hormone levels in the winter and depressed plasma cortisol and insulin concentrations during wintertime food deprivation. However, these parameters were not previously tested in the wild population. In the present study 37 wild raccoon dogs were sampled at different seasons and diverse biochemical variables were determined. The results mostly confirmed previous observations on farmraised raccoon dogs. The liver glycogen stores increased during the autumnal fattening period but were low in the winter. The liver glycogen phosphorylase activity decreased but lipase activity increased in the winter indicating the use of fat as the principal metabolic fuel. The plasma insulin concentrations were low in the winter allowing the release of fatty acids from adipose tissue. Low wintertime cortisol and thyroid hormone levels could contribute to protein sparing. Unlike on farms, wild raccoon dogs did not show seasonal fluctuations in their plasma ghrelin or growth hormone levels. The observed physiological phenomena emphasise the adaptation of the species to long periods of food scarcity in the winter.     

Continuous melatonin treatment and fasting in the raccoon dog (Nyctereutes procyonoides)--vernal body weight regulation and reproduction

The raccoon dog (Nyctereutes procyonoides) is a canid omnivore with marked seasonal changes in its body adiposity. The aim of this study was to investigate the roles of melatonin, leptin, ghrelin and growth hormone (GH) in weight regulation and reproduction of the species. Sixteen raccoon dogs were treated with continuous-release melatonin implants in Aug 2000 and in Feb 2001 (the MEL group) and 16 animals were sham-operated (the SHAM group). Half of the raccoon dogs were fasted between Nov 27(th) 2000 and Jan 25(th) 2001. The autumnal results have been previously published and this paper reports the vernal data. The leptin concentrations of the SHAM females were high before the mating season, decreased before estrus, increased during gestation and reduced after parturition. The MEL females had higher leptin concentrations than the SHAM females in early March, whereas the MEL males had lower leptin concentrations than the SHAM males in late March. Also the ghrelin and GH concentrations of the SHAM females decreased before estrus. Continuous melatonin treatment advanced the vernal rise in the ghrelin concentrations and the vernal drop and the subsequent rise in the GH concentrations of the females. Melatonin also increased their body mass indices from July to Aug 2001, indicating that it triggers the autumnal accumulation of fat in the species.     

Endocrine response to fasting in the overwintering captive raccoon dog (Nyctereutes procyonoides)

The raccoon dog (Nyctereutes procyonoides) is an omnivorous canid utilizing the passive wintering strategy in the boreal climate. Farmed raccoon dogs (n=12) were randomly assigned into two study groups on 26 November 2003. Between 3 December 2003 and 27 January 2004, half of the animals were fasted for 8 weeks and plasma weight-regulatory hormone concentrations determined on 26 November and 30 December 2003 and on 27 January 2004. The plasma peptide YY, ghrelin, and growth hormone (GH) concentrations increased due to food deprivation, while the T4 and Acrp30 concentrations decreased. Furthermore, the plasma GH concentrations were higher in the fasted raccoon dogs than in the fed animals, which had higher plasma insulin, glucagon, and T4 concentrations. However, fasting had no effect on the plasma leptin concentrations. The results confirm previous findings with unchanged leptin levels in fasting carnivores. Increased GH levels probably contribute to increased lipolysis and mobilization of fat stores. Ghrelin can also enhance lipolysis by increasing the GH levels. The decreased levels of T4 may reduce the metabolic rate. The plasma dopamine concentrations decreased due to fasting unlike observed previously in rats. Together with the unaffected adrenaline, noradrenaline, and cortisol concentrations, this suggests that food deprivation in winter does not cause stress to the raccoon dog but is an integral part of its natural life history.     

Seasonal reproductive endocrine profile of the raccoon dog (Nyctereutes procyonoides)-effects of melatonin and food deprivation

The raccoon dog (Nyctereutes procyonoides, Canidae, Carnivora) is a middle-sized omnivore with excessive autumnal fattening and winter sleep. We studied adaptations of the species to boreal climate and photoperiod by following the plasma reproductive and thyroid hormone concentrations of farm-bred raccoon dogs (n=32) for 12 months. On August 16, 2000, and February 8, 2001, half of the raccoon dogs received continuous-release melatonin implants (the MEL group). The other half was sham-operated (the SHAM group). Between November 27, 2000, and January 25, 2001, half of the animals of both groups were fasted. The plasma testosterone concentrations of the MEL males peaked in February, a month earlier than in the SHAM males. Autumnal melatonin treatment also advanced the gestation period reflected by the plasma progesterone concentrations by seven weeks. Food deprivation in winter seems to accentuate the sex steroid response during the mating as the fasted males had higher testosterone concentrations than the fed males in February and March.     

Effects of seasonality and fasting on the plasma leptin and thyroxin levels of the raccoon dog (Nyctereutes procyonoides) and the blue fox (Alopex lagopus)

Plasma leptin and thyroxin concentrations of eleven raccoon dogs and eleven blue foxes were monitored for 6 months. Half of the animals were placed on a 3-week fast in November. Leptin levels were low in summer, but in October they rose significantly. In November, leptin concentrations decreased rapidly within a week although the body mass of the animals remained stable. There were no significant differences between experimental groups for raccoon dogs, but in blue foxes the fasting group had lower leptin levels than the control group. High thyroxin levels in summer decreased as autumn progressed, but thyroxin concentrations of the fasting groups increased at the end of the fast. Leptin levels of the raccoon dog and the blue fox are not determined only by the fat reserves of the animals, but they seem to reflect the autumnal deposition of fat at the onset of winter. Blue foxes have metabolic rates of active animals during the winter and higher leptin levels in December than raccoon dogs. The superficially hibernating raccoon dogs have low leptin levels after the onset of winter perhaps as an adaptation to fasting. J. Exp. Zool. 289:109-118, 2001.     

Circannual leptin and ghrelin levels of the blue fox (Alopex lagopus) in reference to seasonal rhythms of body mass, adiposity, and food intake

The aim of the study was to investigate the circannual rhythms of leptin and ghrelin in the blue fox, a variant of the endangered arctic fox, in relation to its seasonal cycles of body mass, adiposity and food intake. The effects of long-term fasting and exogenous melatonin treatment on these weight-regulatory hormones were also investigated. The leptin concentrations of the blue fox increased during the autumnal accumulation of fat and decreased during the wintertime and vernal weight loss periods. The leptin levels peaked 2-6 weeks before the maximum values were observed for the body mass indices, voluntary food intake, and body masses. The ghrelin concentrations fluctuated widely during the autumn but decreased in the winter in association with suppression of food intake. Exogenous melatonin advanced the seasonal changes in the food intake of the blue fox but did not affect the seasonal rhythms of leptin and ghrelin concentrations. The leptin concentrations did not respond to the 3-week fasting periods in a consistent way, but the ghrelin levels increased due to food deprivation. In addition to the amount of fat in the body the leptin secretion of the blue fox may be regulated also by other factors. The blue fox may also express seasonal changes in its leptin sensitivity. Our results reinforce the hypothesis that leptin does not function as an acute indicator of body adiposity in seasonal carnivores but rather as a long-term signal of nutritional status.     

Role of adiposity hormones in the mouse during fasting and winter-acclimatization

The influence of fasting and winter-acclimatization (cold and short-day acclimatization) on mouse plasma leptin, ghrelin, growth hormone (GH) and melatonin concentrations was determined from blood samples taken at mid-day and midnight. A 16-h fast decreased the plasma leptin but almost doubled the plasma ghrelin concentrations which contribute to energy saving, appetite stimulation and, in the case of leptin, to inhibition of reproduction. Winter-acclimatization did not affect plasma ghrelin concentrations, whereas leptin decreased to the same level as in fasting. The low leptin concentrations possibly enable an increased caloric intake for the purpose of thermogenesis. Fasting and winter-acclimatization seemed to abolish the diurnal leptin rhythm, but had no effect on that of ghrelin. Plasma melatonin concentration correlated negatively with ghrelin, suggesting a possible role for melatonin in the regulation of ghrelin concentration. SNS-activity and insulin appear to be the main regulators of leptin plasma concentration in the mouse, rather than melatonin as in some seasonal mammals. Interestingly, endogenous ghrelin did not stimulate GH secretion, which is a well-documented reaction to exogenous ghrelin injections.     

Seasonality and fasting effect in raccoon dog Nyctereutes procyonoides serum leptin levels determined by canine leptin-specific enzyme-linked immunosorbent assay

Leptin is an adipocyte-derived peptide hormone that acts on the brain and regulates food intake and energy balance. Several previous reports have suggested that overwintering raccoon dogs Nyctereutes procyonoides are able to control their adiposity efficiently, but the contribution of leptin to weight regulation in these animals remains unclear. To study the seasonality of overwintering raccoon dogs as well as the effects of fasting on them, serum leptin levels were investigated using a newly established canine leptin-specific enzyme-linked immunosorbent assay (ELISA) kit. Of the nine animals studied, five were fed and four were fasted (deprived of food for 2 months in winter). Blood samples and body fat weights were monitored once a month throughout the experimental period (July 2007-March 2008). Leptin concentrations obtained by ELISA were significantly higher than and had a positive correlation with those obtained by previously used multispecies radioimmunoassay (RIA) kits. Moreover, ELISA showed a clearer correlation between the body fat weight and leptin levels compared with RIA, suggesting the efficacy of canine leptin-specific ELISA kit for leptin estimation in raccoon dogs. Autumnal fattening was observed in both groups of animals, but the wintertime loss of adipose tissue was more obvious in the fasted group. Serum leptin concentrations determined by ELISA showed seasonal changes without significant differences between the fed and fasted animals. Therefore, high levels of leptin may be responsible for the suppression of feeding behavior in raccoon dogs before winter.     

Effects of season,food deprivation and re-feeding on leptin,ghrelin and growth hormone in arctic foxes (<Emphasis Type="Italic">Alopex lagopus</Emphasis>) on Svalbard,Norway

The arctic fox (Alopex lagopus) is a medium-sized predator of the high Arctic experiencing extreme seasonal fluctuations in food availability, photoperiod and temperature. In this study, the plasma leptin, ghrelin and growth hormone (GH) concentrations of male arctic foxes were determined during a food deprivation period of 13 days and the subsequent recovery in November and May. Leptin, ghrelin and GH were present in arctic fox plasma in amounts comparable to other carnivores. The plasma leptin concentrations did not react to food deprivation unlike in humans and rodents. However, the leptin levels increased during re-feeding as an indicator of increasing energy reserves. The relatively high ghrelin–leptin ratio, decrease in the plasma ghrelin concentration, an increase in the circulating GH concentrations and the observed negative correlation between plasma ghrelin and free fatty acid levels during fasting suggest that these hormones take part in the weight-regulation and energy metabolism of this species by increasing fat utilisation during food deprivation. The results strengthen the hypothesis that the actions of these weight-regulatory hormones are species–specific and depend on seasonality and the life history of the animals.Abbreviations FFA free fatty acid - GH growth hormone - RMR resting metabolic rate Communicated by G. Heldmaier     

Ghrelin promotes slow-wave sleep in humans

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 x 50 microg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans (n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated delta-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200-0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.     

Detection, analysis and interactions of plasma ghrelin, leptin and growth hormone in the mink (Mustela vison)

The aim of this study was to obtain basic knowledge of the plasma concentrations and interactions of weight regulatory hormones in juvenile minks (Mustela vison). Ghrelin, leptin, and growth hormone (GH) levels were validated and determined by radioimmunoassay methods from the plasma of 30 female and 30 male minks. The female minks had higher plasma ghrelin and GH levels than the males. The plasma ghrelin concentrations of the females correlated positively with their body masses (BMs). The plasma leptin levels did not differ between sexes, but there was a positive correlation between the plasma leptin concentrations and BMs in the male minks. When the data from the male and female minks were combined, the correlation between the leptin levels and the BMs was still clear, but this was not observed in the females alone. In the male minks, the plasma GH levels correlated positively with the BMs and with the plasma leptin concentrations. However, there was no correlation between the plasma ghrelin and GH or leptin concentrations. The hormone concentrations were quite similar to earlier measurements in other carnivores.     

Adaptations of the raccoon dog (Nyctereutes procyonoides) to wintering--effects of restricted feeding or periodic fasting on lipids, sex steroids and reproduction

The raccoon dog (Nyctereutes procyonoides) is an omnivorous canid with autumnal hyperphagia and fattening followed by mid-winter passivity and fasting in boreal latitudes with seasonal snow cover. The effects of two different feeding levels (400 or 200 kcal/animal/d) or fasting (5-week fasting+1-week feeding+3-week fasting) on plasma lipids, sex steroids and reproductive success of farm-bred raccoon dogs (n=60 females and 24 males) were studied in winter. The body masses, body mass indices (BMIs) and levels of plasma triacylglycerols (TG), total cholesterol and low- and high-density lipoprotein cholesterol did not differ between the fed and the restrictively fed animals. During fasting, the plasma TG concentrations increased and the BMIs decreased, indicating the release of fatty acids from adipose tissue. After the fasting periods, the levels of plasma cholesterol and high-density lipoprotein cholesterol increased, whereas the TG levels decreased indicating the rebuilding of energy reserves. The fact that the different wintertime feeding regimes had no impact on the plasma glucose, total protein, cortisol, estradiol, progesterone or testosterone levels, or on the reproductive success, indicates versatile adaptive capacity in the species.     

Plasma ghrelin levels in patients with end-stage renal disease

Ghrelin is an acylated peptide stimulating secretion of the growth hormone (GH). It was originally isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor. Although being predominantly produced by endocrine cells of the gastric fundus, its secretion has been found in various tissues including the kidney. To study the influence of renal failure on plasma ghrelin levels we examined 16 patients with end-stage renal disease (ESRD) receiving hemodialysis (8 men and 8 women) and 19 controls (10 men and 9 women). Both groups were comparable in age and BMI. In all subjects we assessed plasma levels of ghrelin, leptin, soluble leptin receptor, insulin, IGF-I, IGFBP-1, IGFBP-3 and IGFBP-6. Ghrelin levels were significantly higher in the group of dialyzed patients (4.49+/-0.74 vs. 1.79+/-0.15 ng/ml; p<0.001). These patients had significantly higher levels of GH, IGFBP-1, IGFBP-6, leptin and percentage of body fat (p<0.05). In the group of patients with ESRD plasma ghrelin levels positively correlated with IGFBP-1 (p<0.01). In the control group, ghrelin positively correlated with GH concentrations (p<0.01) and negatively correlated with the levels of insulin and creatinine (p<0.05). In conclusion, patients with ESRD have higher ghrelin concentrations, which might be caused by a decreased excretion/metabolism of ghrelin in the kidney during renal failure.     

Thermoregulatory adaptations of the overwintering captive raccoon dog (Nyctereutes procyonoides) in boreal climate

The raccoon dog (Nyctereutes procyonoides) is a nocturnal canid thought to utilise passive wintering strategy in the boreal climate. To record the deep body temperature (T(b)), 12 farmed raccoon dogs were implanted with intra-abdominal T(b) loggers on November 26, 2003. Between December 3, 2003 and January 27, 2004 half of the animals were fasted for 8 weeks. The amplitude of the diurnal T(b) oscillations increased due to fasting. However, the mean diurnal T(b) was lower in the fasted animals only during two occasions. Unlike observed previously in other species, not only did the raccoon dogs experience hypothermia between 0600 and 1000 hr but also hyperthermia between noon and 1800 hr. The fasted animals were as active as the fed animals measured after 42-43 days of fasting and there was a significant cross-correlation between physical activity and T(b). The nocturnal period of hypothermia is probably an adaptation to save energy during food deprivation. The diurnal hyperthermia could be explained by the opportunistic foraging behaviour of the species. Opposite to the established assumptions, the raccoon dog does not seem to enter winter sleep on fur farms. In the future it is important to determine if true winter sleep occurs in nature in the species.     

Seasonal changes in serum leptin of the feral raccoon (Procyon lotor) determined by canine-leptin-specific ELISA

Several reports have been published on blood leptin concentrations in feral animals, including members of the Carnivora, using a commercially available multi-species radioimmunoassay (RIA) kit with anti-human leptin antibody. However, we observed weak immunoreactivity between recombinant canine leptin and anti-human leptin antibody, suggesting a limitation in the applicability of the RIA kit for leptin assays in Carnivora species. We tested the applicability of RIA and sandwich enzyme-linked immunosorbent assay (ELISA) with anti-canine leptin antibody to assay blood leptin in the dog (Canis familiaris) and the raccoon (Procyon lotor). When RIA was used for recombinant canine leptin and dog sera, values were much lower than those determined by ELISA at higher concentrations (>10 ng/ml), while rather higher at lower concentrations (<2 ng/ml). A similar discrepancy between the two methods was found for serum leptin concentrations in raccoons. Clear seasonal variations were observed by ELISA, but not by RIA, with high values in autumn (3.46+/-0.45 ng/ml) and low values in spring and summer (0.71+/-0.07 ng/ml). Serum leptin concentrations in raccoons correlated positively with their body weight (r=0.753) and body mass index (r=0.755), corroborating our previous findings of a strong positive correlation between serum leptin concentrations and body fat content in dogs. Thus, the canine leptin ELISA is useful for assays of dog and raccoon leptin, and blood leptin is a good marker of nutritional condition in the species of Carnivora assayed in this study.     

Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents

Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa (AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone (GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min (from 2000 to 0800) in 23 AN and 21 controls 12-18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls (P < 0.0001) subsequent to decreased burst mass (P < 0.0001) and basal secretion (P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/creatinine (15% of variability). Valley leptin predicted cortisol half-life (22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition.     

Plasma levels of total and active ghrelin in acromegaly and growth hormone deficiency

Ghrelin is an endogenous growth hormone (GH) secretagogue recently isolated from the stomach. Although it possesses a strong GH releasing activity in vitro and in vivo, its physiological significance in endogenous GH secretion remains unclear. The aim of this study was to characterize plasma ghrelin levels in acromegaly and growth hormone deficiency (GHD). We investigated plasma total and active ghrelin in 21 patients with acromegaly, 9 patients with GHD and 24 age-, sex- and BMI-matched controls. In all subjects, we further assessed the concentrations of leptin, soluble leptin receptor, insulin, IGF-I, free IGF-I and IGFBP-1, 2, 3 and 6. Patients with acromegaly and GHD as well as control subjects showed similar levels of total ghrelin (controls 2.004+/-0.18 ng/ml, acromegalics 1.755+/-0.16 ng/ml, p=0.31, GHD patients 1.704+/-0.17 ng/ml, p=0.35) and active ghrelin (controls 0.057+/-0.01 ng/ml, acromegalics 0.047+/-0.01 ng/ml, p=0.29, GHD patients 0.062+/-0.01 ng/ml, p=0.73). In acromegalic patients plasma total ghrelin values correlated negatively with IGF-I (p<0.05), in GHD patients active ghrelin correlated with IGF-I positively (p<0.05). In the control group, total ghrelin correlated positively with IGFBP-2 (p<0.05) and negatively with active ghrelin (p=0.05), BMI (p<0.05), WHR (p<0.05), insulin (p=0.01) and IGF-I (p=0.05). Plasma active ghrelin correlated positively with IGFBP-3 (p=0.005) but negatively with total ghrelin and free IGF-I (p=0.01). In conclusion, all groups of the tested subjects showed similar plasma levels of total and active ghrelin. In acromegaly and growth hormone deficiency plasma ghrelin does not seem to be significantly affected by changes in GH secretion.     

Seasonal and diurnal melatonin production in exercising sled dogs

Melatonin is a hormone that is released from the pineal gland into the blood stream and is controlled by nerve impulses from the suprachiasmatic nuclei. Melatonin synthesis, which is inhibited by light on the mammalian retina, peaks in plasma concentrations during the night. Though still a subject of intense research, melatonin in mammals is known to effect the reproductive system, thyroid function, and adaptations to seasonal changes. Sled dogs in Fairbanks, Alaska (65 degrees N) can be exposed to anywhere from 21 h of daylight in the summer to 4 h in the winter. While light may be the primary factor influencing melatonin production, we hypothesized that exercise may also affect melatonin production. In the current study, sled dogs were used to study seasonal and diurnal variation in melatonin production. Sled dogs by nature are elite athletes and therefore exercise was a focus in the study. Both exercise and non exercise dogs from 2 distinct latitudes were used. The peak in melatonin production was prolonged in high latitude dogs (65 degrees N), compared with lower latitude dogs (45 degrees N). Dogs at both latitudes show a reduction in peak melatonin levels with exercise, and winter melatonin levels in both locations were higher than the summer. Surprisingly, sled dogs in Alaska had lower melatonin levels than sled dogs in New York.     

Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice

We have previously shown that growth hormone (GH) overexpression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AgRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR-/- and littermate control (+/+) mice to determine whether ghrelin's acute effects on appetite are dependent on GHR signaling. GHR-/- mice were also analyzed with respect to serum levels of lipoproteins, apolipoprotein (apo)B, leptin, glucose, and insulin as well as body composition. Central injection of ghrelin into the third dorsal ventricle increased food consumption in +/+ mice, whereas no change was observed in GHR-/- mice. After ghrelin injection, AgRP mRNA expression in the hypothalamus was higher in +/+ littermates than in GHR-/- mice, indicating a possible importance of AgRP in the GHR-mediated effect of ghrelin. Compared with controls, GHR-/- mice had increased food intake, leptin levels, and total and intra-abdominal fat mass per body weight and deceased lean mass. Moreover, serum levels of triglycerides, LDL and HDL cholesterol, and apoB, as well as glucose and insulin levels were lower in the GHR-/- mice. In summary, ghrelin's acute central action to increase food intake requires functionally intact GHR signaling. Long-term GHR deficiency in mice is associated with high plasma leptin levels, obesity, and increased food intake but a marked decrease in all lipoprotein fractions.     

Ghrelin, macronutrient intake and dietary preferences in long-evans rats

Ghrelin is a recently discovered peptide that is primarily produced by the stomach. As a ligand of the growth hormone (GH) secretagogue (GHS) receptor, it stimulates GH secretion but it also stimulates feeding and has adipogenic effects in rodents. Although its circulating levels are modulated by fasting and refeeding, its relationship with diet composition is not known. In the present paper, we measured plasma ghrelin as well as two important hormones (leptin and insulin) in Long-Evans rats placed in two different feeding situations, e.g., either with imposed diets or with food choice. In the first case, the rats were fed unbalanced diets (either high-carbohydrate (HC) or high-fat (HF) diets) for 14 weeks, whereas in the second situation, they had the choice between these 2 diets for 2 weeks and were selected for their fat or carbohydrate preference. The intake of the HF diet for 14 weeks was associated with lower levels of ghrelin (-30% vs control diet; P < 0.01). These levels increased when the percentage of carbohydrate in the diet increased (+26 to +42% vs control diet; P < 0.01 or less). Ghrelin was inversely correlated with plasma leptin (r = -0.55; P < 0.003) and blood glucose (r = -0.58; P < 0.001) as well as with body weight (r = -0.63; P < 0.0001) and body fat content estimated by the sampling of specific fat pads (r = -0.62; P < 0.0001). In the food choice experiment, fat-preferring rats had plasma ghrelin levels lower than the carbohydrate-preferring rats (-33%; P < 0.0002). Ghrelin secretion was therefore very sensitive to the diet composition. Its down-regulation by fat ingestion might serve as a counterregulatory mechanism to limit the development of dietary-induced adiposity. Ghrelin may signal when a high calorie diet is ingested.