Galanin receptor antagonists decrease fat preference in Brattleboro rat.

The Brattleboro rat eats spontaneously 46% of its diet per day in fat when given a choice of carbohydrate, protein and fat. An overexpression of galanin (GAL) has been also observed in the hypothalamic paraventricular nuclei (PVN). This associative correlation has led to a hypothesis of a functional relation between central galanin expression and the preference for a lipid diet. In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated. Both antagonists were injected into either the cerebral ventricles or directly above the PVN, and the diet consumption followed for the subsequent 24h. C7 decreased significantly fat consumption when injected into the ventricles or directly above the PVN. In contrast, galantide must be injected above the PVN to show the same effect. However, the two antagonists did not modify GAL mRNA expression in the PVN when they were injected 2h before sacrifice. These experiments confirm a functional link between the preferential consumption of fat and hypothalamic Galanin; different subtypes of the GAL receptor are probably involved, since both Galanin antagonists were differently efficient in decreasing spontaneous fat selection of the Brattleboro rat.

Plasma leptin and hypothalamic neuropeptide Y and galanin levels in Long-Evans rats with marked dietary preferences.

Neuropeptides present in the hypothalamus and new messengers in the periphery such as leptin modulate food intake in mammals. Neuropeptide Y (NPY) and galanin in microdissected brain areas and plasma leptin levels were measured by specific radioimmunoassays during the resting period in rats selected for their strong preference either for carbohydrate or fat, but with identical energy intake. NPY concentrations were 23% lower (p <.02) in carbohydrate-preferring (CP) than in fat-preferring (FP) rats in the parvocellular part of the paraventricular nucleus (PVN), which is one of the main areas involved in the regulation of feeding behavior. On the other hand, galanin was significantly (+25%, p = .03) higher in CP rats than in FP rats in the magnocellular part of the PVN. Plasma leptin was more than 50% higher in FP rats than in CP rats (p < .01) and highly correlated with the fat preference (r = 0.57; p = .003) and body weight gain. We conclude that the rats with a spontaneous and marked dietary preference have a characteristic peptidergic profile. Due to their anatomical relationships, neuropeptide Y could act in conjunction with galanin in a peptidergic balance located in the paraventricular nucleus. This model integrates information provided by the energy stores and translated by peripheral messengers such as leptin which could act in a counterregulatory manner in order to limit the overweight induced by the ingestion of unbalanced diets.

Dietary preferences of Brattleboro rats correlated with an overexpression of galanin in the hypothalamus.

Galanin (GAL) is a neuropeptide cosynthesized with vasopressin (AVP) in neurons of the hypothalamo-neurohypophysial system. It increases food intake when injected into the brain and elicits an overconsumption of fat. The Brattleboro rat (DI) is genetically unable to produce AVP; the AVP-deficient-producing neurons of the hypothalamo-neurohypophysial system of DI rats are chronically stimulated and DI rats suffer from diabetes insipidus. We studied the central expression of GAL and the dietary preferences in the DI rat. GAL was overexpressed in the hypothalamus of the DI rat. GAL mRNA was higher by 1.8-fold in the supraoptic (P < 0.05) and by four-fold in the paraventricular nuclei (P < 0.001) of male and female DI rats compared with those of control Long Evans (LE) rats. However, GAL mRNA was lower in the arcuate nuclei of DI rats and equal to that of LE rats in the dorsomedian nuclei. We also measured a high preference for a lipid diet (45% of the daily consumption) when DI rats ate from a choice of the three macronutrients. Chronic infusion with deamino-8D-AVP (agonist of AVP V2 receptors) prevented the diabetes insipidus and the chronic stimulation of the hypothalamo-neurohypophysial system of the DI rats. However, the treatment did not suppress the overexpression of GAL, nor did it affect the rats' preference for a lipid diet. We conclude that the DI rat provides a novel animal model in which a spontaneous dietary preference correlates with the overexpression of one of the hypothalamic peptides, GAL.

Evidence that hypothalamic neurotensin signals leptin effects on feeding behavior in normal and fat-preferring rats.

Leptin inhibits food intake when it is injected in the periphery or in the central nervous system. It is likely that its action is not only mediated by the inhibition of orexigenic peptides such as neuropeptide Y. Therefore, we characterized the pharmacological and physiological relationships of leptin with neurotensin (NT), a central feeding inhibitor. Firstly, we investigated the central interactions of leptin and NT. Intracerebro-ventricular (ICV) injection were done in normal Long-Evans rats. NT had a short lasting (30 minutes; p<0.01) inhibitory effect on spontaneous food intake measured at the beginning of the dark phase whereas the effect of ICV leptin was observed after 24 hours (p<0.001). Co-injection with leptin potentiated NT effect at 30 minutes (p<0. 001) and prolonged it for 30 additional minutes (p<0.01). In addition, NT potentiated the effect of leptin at 30 and 60 minutes (p<0.02 and p<0.001 respectively) but not at 24 hours. Secondly, we observed that NT concentrations were augmented in selective brain areas in fat-preferring rats (+ 34% for hypothalamic NT; p<0.03). This increase was observed in the parvocellular part of the paraventricular nucleus (PVNp) only and was associated with an increase in circulating leptin levels (+ 75%; p<0.003). Interestingly, plasma leptin and NT in the PVNp were strongly correlated (r=0.57; p<0.003), suggesting changes of NT processing or release in this nucleus. These results strongly suggest that the short-term anorexigenic effects of leptin in normal rats are at least partly mediated by changes in NT processing or release. They also suggest that these processes take place in the hypothalamus, most probably in the PVNp and that they might be sensitive to fat ingestion. Therefore, the neurotensin increase observed in fat-preferring rats would limit the overconsumption of energy, a physiological mechanism translated by leptin.

Hypothalamic neuropeptide Y content and mRNA expression in weanling rats subjected to dietary manipulations during fetal and neonatal life.

Hypothalamic neuropeptide Y (NPY) is present very early during the fetal life and is rapidly functional in the regulation of feeding behavior after birth. In the present experiment, we tried to determine the influence that the diet type ingested by dams during gestation and lactation would have on the growth and hypothalamic and pancreatic peptides of their progeny immediately after weaning. The dams were fed on either a high-carbohydrate (HC), a high-fat (HF) or a control diet ad libitum. At 3 days of age, the HC pups weighed significantly more than the two other groups (P < 0.02 vs. C and P < 0.002 vs. HF). At weaning, the HF rats were significantly lighter than the two other groups (P < 0.001). Food intake was significantly lower in the HF rats than in the two other groups 3 days (P < 0.002) and 5 days after weaning (P < 0.02). Plasma glucose of the HF rats was significantly lower than that of the control rats (P < 0.05) and of the HC rats (P < 0.01). Immunoreactive insulin in the HF rats was also significantly lower than that in the control rats (-53%; P < 0.001) and in the HC rats (-47%; P < 0.001). NPY content and mRNA expression in the arcuate nucleus were not significantly different between the three groups. NPY concentration only varied in the ventromedian nucleus. In the control rats, it was significantly lower than that of the HC rats (-35%; P < 0.01) and that of the HF rats (-32%; P < 0.002). These data demonstrated that the regulatory mechanisms of feeding behavior in offspring are completely and differentially modified by the macronutrient content of the diets ingested by their mother. Both peripheral and central mediators were strongly implicated. These modifications could have long-term repercussions on body weight and composition.

Hypothalamic neuropeptide Y and plasma leptin after long-term high-fat feeding in the rat.

The ingestion of fat by rodents affects the level of neuropeptide Y (NPY) in the hypothalamus and we hypothesized that they might be linked via leptin, the adipose tissue hormone. The influence of fat intake on leptin and NPY levels was studied in rats fed on either a high-fat (HF) or a low fat diet (LF) for 5 months. Ingestion of the HF diet increased fat deposition (+48%; P < 0.01), leptinemia (+189%; P < 0.001) and reduced NPY levels in the arcuate nucleus (-35%; P < 0.01) and in the paraventricular nucleus (-22%; P < 0.01). However, although leptin levels reflected the amount of relative fat deposition (r = 0.62; P < 0.01), we found no evidence for a direct relationship between plasma leptin and NPY levels in the hypothalamus. These results suggest that the long-term effects of fat intake on NPY concentrations in the hypothalamus and plasma leptin are associated with different regulatory mechanisms.

Dietary preferences in monosodium glutamate-lesioned rats: age-variable influence of hypothalamic neuropeptide Y.

In this study, we measured hypothalamic neuropeptide Y (NPY) and the food preference in weanling and adult monosodium glutamate (MSG)-lesioned and control rats. The MSG lesion was induced by three subcutaneous injections (4 g/kg body wt) during the first week of life of the rats. All treated and control weanling rats strongly preferred a high carbohydrate (HC) diet to a high fat (HF) diet. Adult control rats ate 60% more HF diet (P < 0.001) and 25% less HC diet (P < 0.01) than MSG-treated rats. At weaning and in adulthood, NPY concentrations in MSG-rats were markedly lower in the arcuate and paraventricular nuclei (P < 0.01 or less) than in control rats. The MSG treatment did not affect carbohydrate preference observed at weaning. It was associated with a limited development of fat appetite in adulthood. NPY could influence the dietary preferences more in adulthood, likely when all neuropeptidergic systems are mature.

Enhanced feeding response to neuropeptide Y in hypothalamic neuropeptide Y-depleted rats.

Monosodium glutamate is neurotoxic for the arcuate nucleus and more generally for all circumventricular organs when injected in newborn rats. Neuropeptide Y, a potent stimulator of food intake, is mainly synthesized in the arcuate nucleus. In the present experiment, we determined the hypothalamic status and the feeding response to intracerebroventricular neuropeptide Y in adult rats neonatally treated with monosodium glutamate. Marked neuropeptide Y decreases were measured in the arcuate nucleus and in the paraventricular nuclei in monosodium glutamate-treated rats (-40%; P < 0.01). Adult rats neonatally treated with monosodium glutamate weighed significantly less (-8%; P < 0.01) and ate less (-10%; P < 0.01) than the control rats. Neuropeptide Y injections in a lateral brain ventricle stimulated food intake in control and monosodium glutamate-treated rats in a dose-dependent manner (P < 0.001). Whatever the time after drug injection (2, 4, 6 and 8 h) and the injected dose (0.5, 1 and 5 micrograms), feeding responses were always greater in monosodium glutamate-treated rats (about 2 times greater starting with the lowest dose (0.5 microgram): 9.3 +/- 1.0 (monosodium glutamate) vs. 5.3 +/- 0.7 (control) g/2 h, P < 0.01). Calculated minimal effective doses were also always smaller in monosodium glutamate-treated rats than in control animals (P < 0.01). Neuropeptide Y increased meal duration, meal size and decreased latency to initiate feeding in monosodium glutamate-treated rats (P < 0.01) and control rats (P < 0.01). For each dose of neuropeptide Y, effects were more pronounced on meal size (+70%) and meal duration (+25%) in monosodium glutamate-treated rats than in control rats. Therefore, monosodium glutamate-treated rats were more sensitive to exogenous neuropeptide Y. Decreased food intake in the monosodium glutamate-treated rats was associated with a decrease in neuropeptide Y concentrations in the arcuate-paraventricular axis. This confirms the functional role of this peptidergic pathway in eating behavior.

Opposite influence of carbohydrates and fat on hypothalamic neurotensin in Long-Evans rats.

Neurotensin inhibits food intake when injected in the central nervous system and is released after fat ingestion. The aim of the present study was to measure it in different brain areas and to determine if it is involved in the long-term variations in food intake induced by the ingestion of a high-fat (HF) diet. We compared the results with those obtained with 2 low-fat [high-carbohydrates (HC)] diets and a well-balanced diet. For this purpose, weanling male Long-Evans rats were fed ad libitum for 14 weeks either on a control diet, a HF diet or a HC diet. The rats with the HC (high-starch) diet were divided into 2 subgroups: the first (HC) drank water and the second (HCS) drank a 25% sucrose solution. During the last week of the experiment, energy intake of the HCS rats was significantly greater than that of the 3 other groups of rats (+17.2%; p < 0.01; +27.1%; p < 0.001 and +34.6%; P < 0.001 vs the control, HC and HF rats respectively). NT did not vary in the midbrain and particularly in the ventral tegmental area. Its concentrations were significantly higher in the 2 HC groups than in the HF rats both in the paraventricular (PVN; p < 0.02) and dorsomedial nuclei (DMN; p < 0.03). In the DMN, they were positively correlated with energy intake (r = 0.39; p = 0.027). These results indicate that hypothalamic neurotensin is indeed involved in the long-term modulation of feeding behavior by diet composition and that fat is the more potent macronutrient for its regulation.

Hypothalamic neuropeptides could mediate the anorectic effects of fenfluramine.

Oxytocin, vasopressin and corticotrophin releasing factor have anorectic properties when injected centrally. We studied the kinetics of these neuropeptides by injecting fenfluramine, a drug which reduces food intake, in Long Evans rats. The drug was injected daily through a double chronic cannula implanted above the paraventricular nucleus of the hypothalamus; the rats had free access to pure macronutrients. The rats lost weight during the treatment. Their total caloric intake decreased mostly because the carbohydrate intake decreased, while the protein intake increased slightly. The synthesis and release of brain oxytocin and vasopressin were increased and the release of corticotrophin releasing factor was stimulated. The neuropeptides could be involved in fenfluramine-triggered mechanisms.

Macronutrient type independently of energy intake modulates hypothalamic neuropeptide Y in Long-Evans rats.

Neuropeptide Y (NPY) induces a robust feeding response when it is injected in the hypothalamus. It stimulates both carbohydrate and fat intakes. Diets rich in either macronutrient are known to induce obesity and to modify feeding behavior. The aim of the present study was to determine the effects of long-term ingestion of these diets on hypothalamic NPY in relation with food intake and body weight gain and composition. For this purpose, three groups of weanling Long-Evans rats were fed either a well-balanced diet, a high-carbohydrate (HC) diet (high starch plus 25% sucrose solution), or a high-fat (HF) diet during 14 weeks. Body weight and food intake were recorded during this period. At the end of the experiment, NPY was measured in several microdissected brain areas, and some adipose tissues (AT) depots were sampled. HF rats weighed significantly more than the two other groups (p < 0.02). They were also fattier (+ 30-50% in AT weights; p < 0.01). Energy intake (EI) of the HC rats was significantly greater than that of the control (+ 15%; p < 0.02) and HF rats (+ 34%; p < 0.01) during the week preceding killing. EI of HF rats over the whole experiment was lower than that of the two groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Corticotropin-releasing factor and anorexia nervosa: reactions of the hypothalamus-pituitary-adrenal axis to neurotropic stress]. / Système corticolibérinergique et anorexie mentale: réactions du système hypothalamo-hypophyso-corticosurrénalien à un stress neurotrope.

The aim of this study is to obtain CRF (Corticotropin Releasing Factor) stimulation at a suprahypothalamic level with a psychological stressor and to evaluate its response in anorexia nervosa. CRF plays a major role in the mechanisms underlying the hypothalamo-pituitary-adrenal (HPA) system's response to stress. Animal studies clearly showed that CRF is involved both in the adaptation to a novel environment and the regulation of eating behaviour. CRF's staietogenic effect is mediated via the paraventricular nucleus. Three groups of age matched young women were studied: 8 patients meeting the DSM III-R criteria for anorexia nervosa, 8 underweight healthy volunteers and 10 normal weight volunteers. All subjects were submitted to an auditory stimulation test ("psychosocial stress test") consisting of an intellectual task in which maximal performance is impossible to achieve, the subjects being permanently disturbed by various meaningful noises. Subjects were asked to answer self-rating scales for anxiety and tension prior to and after the test. CRF reactivity was measured by salivary cortisol (RIA). After the test, anorexia nervosa patients exhibit a significantly higher salivary cortisol response compared to the normal weight volunteers. In most of cases, salivary cortisol response was not correlated with the psychological variables. The range of the response is very explosive in two anorectic patients. Our data are consistent with the hyperactivity of the corticotropic axis stress response in anorexia nervosa, but request further investigations to prove that.

Galanin in the hypothalamus of fed and fasted lean and obese Zucker rats.

Galanin (GAL), a 29 aminoacid peptide, is widely distributed in the central nervous system and especially in the hypothalamus. It strongly stimulates food intake when it is injected in the paraventricular nucleus (PVN) of normal rats. The obese Zucker rat with a well-established hyperphagia is characterized by a general dysregulation of some important neuropeptides involved in the regulation of feeding behavior e.g. neurotensin, NPY or CCK and the aim of this study was to measure GAL in different microdissected brain areas in lean (Fa/Fa) and obese (fa/fa) male Zucker rats. As feeding status may modulate the central peptide concentrations, it was measured in ad libitum fed rats and in 48-h fasted rats of both genotypes. GAL was measured by a specific radioimmunoassay in the arcuate nuclei (ARC) and parvocellular (PVNp) and magnocellular (PVNm) parts of the PVN as well as in the median eminence (ME), median preoptic area (MPOA), supraoptic (SON) and dorsomedian (DMN) nuclei. Two-way analysis of variance revealed a very significant effect of genotype in the PVNp (P < 0.001), SON (P < 0.001) and in the ME (P < 0.02). No significant variations at all were noted in the ARC, PVNm, MPOA and DMN. GAL concentrations were more than doubled in the PVNp and SON of ad lib obese rats when compared to the ad lib lean rats (P < 0.005). On the other hand, in the ME where GAL concentration was about 4-fold greater than in the other areas, there was a 20 to 30% decrease in GAL concentrations in the obese rat (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of food deprivation and refeeding on the concentration of vasopressin and oxytocin in discrete hypothalamic sites.

Recent evidence has implicated hypothalamic peptides, such as arginine vasopressin (AVP) and oxytocin (OT) in the control of feeding behavior. In this study, we investigated the impact of food deprivation (48 h) and subsequent refeeding (6 h) on the concentration of AVP and OT in discrete hypothalamic areas, as well as in the neurohypophysis. We also estimated in these rats certain peripheral measures, including hydroelectrolytic parameters, plasma and urine AVP, and plasma corticosterone. The results of this study revealed that food deprivation for 48 h produced little change in OT concentration in the various hypothalamic nuclei studied, including the paraventricular and supraoptic nuclei, with the exception of the median eminence (ME), where a significant decline (-36%; p < 0.05) was detected. This effect was not significantly reversed by 6 h of refeeding. With respect to AVP concentration, food deprivation caused a reliable decline exclusively in the parvocellular subdivision of the paraventricular nucleus (pPVN; -45%; p < 0.01) and in the supraoptic nucleus (SON; -45%; p < 0.01). No change in AVP was detected in the ME or in most other hypothalamic nuclei examined. Refeeding for 6 h actually potentiated the effect of food deprivation, decreasing further from baseline the content of AVP in the pPVN and SON. The only other hypothalamic area to exhibit a change in AVP content was the ventromedial nucleus, where AVP level increased (p < 0.001) after deprivation and declined to normal after 6 h of refeeding. The content of AVP and OT in the neurohypophysis was unaffected by food deprivation and subsequent refeeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific hypothalamic neuropeptide Y variation with diet parameters in rats with food choice.

Neuropeptide Y (NPY) preferentially stimulates carbohydrate intake rather than fat intake but there is no information on the effects of food choice on the concentration of NPY in the brain. We measured brain NPY concentrations in male adult rats that had to choose between a high fat and a high carbohydrate diet or were fed a control diet for 2 weeks. In rats with food choice, energy intake increased (+17%). NPY levels increased in the parvocellular part (PVNp) of the PVN and decreased in the lateral hypothalamus and were significantly correlated with the carbohydrate-to-fat energy ratio but not with total energy intake. This suggests that hypothalamic NPY might be involved in food choice and that PVNp is important in the regulation of feeding behaviour by NPY.

Changes in hypothalamic neurotensin concentrations and food intake in rats fed a high fat diet.

Neurotensin (NT), a peptide present both in the brain and in the gastrointestinal tract, has potent anorexigenic effects when centrally injected in rats and is secreted after fat ingestion. High fat diets are often associated with increased energy intake. The aim of this study was therefore to evaluate the role of neurotensin in the feeding behaviour of rats fed on a high fat (HF) diet. Adult Long-Evans rats were fed for two weeks either a control (C) well-balanced diet (n = 10) or a fat-rich diet containing about two-thirds of its energy as fat (margarine and peanut oil; n = 10). Neurotensin was measured by a specific radioimmunoassay in the plasma and in several microdissected brain nuclei involved in the regulation of feeding behaviour. Ingestion of the HF diet induced an increased body weight gain (47.6 +/- 7.7 g (HF) vs. 37.6 +/- 9.3 g (C); P less than 0.05) and an increased energy intake (+ 7.2%; P less than 0.05). Plasma fasting NT concentrations were not affected by the HF diet. In the hypothalamus, significant decreases in NT concentrations were measured in the HF rats in two nuclei important in the regulation of food intake, i.e. the paraventricular nucleus (1.72 +/- 0.16 (HF) vs. 2.27 +/- 0.15 (C) ng/mg protein; P less than 0.05) and the lateral hypothalamus (1.87 +/- 0.16 (HF) vs. 2.37 +/- 0.19 (C) ng/mg protein; P less than 0.05). On the other hand, no variations were measured in the ventral tegmental area, an important site for the metabolism and regulatory action of neurotensin and in other hypothalamic nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Unexpected regulation of hypothalamic neuropeptide Y by food deprivation and refeeding in the Zucker rat.

Neuropeptide Y strongly stimulates food intake when it is injected in the hypothalamic paraventricular (PVN) and ventromedian (VMN) nuclei. In Sprague-Dawley (SD) rats, NPY synthesis in the arcuate nucleus (ARC) is increased by food deprivation and is normalized by refeeding. We have previously shown that the obese hyperphagic Zucker rat is characterized by higher NPY concentrations in this nucleus. NPY might therefore play an important role in the development of hyperphagia. The aim of the present study was to determine if the regulation by the feeding state works in the obese Zucker rat. For this purpose, 10 weeks-old male lean (n = 30) and obese (n = 30) Zucker rats were either fed ad libitum, either food-deprived (FD) for 48 hours or food-deprived for 48 h and refed (RF) for 6 hours. NPY was measured in several microdissected brain areas involved in the regulation of feeding behavior. NPY concentrations in the ARC was about 50% greater in obese rats than in lean rats (p less than 0.02) whatever the feeding state. In the VMN, NPY concentrations were higher in the lean FD rats than in the obese FD rat (p less than 0.001). Food deprivation or refeeding did not modify NPY in the ARC, in the VMN or in the dorsomedian nucleus whatever the genotype considered. On the other hand, food deprivation induced a significant decrease in NPY concentrations in the PVN of lean rats. This decrease was localized in the parvocellular part of this nucleus (43.0 +/- 1.9 (FD) vs 54.2 +/- 2.1 (Ad lib) ng/mg protein; p less than 0.005). Ad lib levels were restored by 6 hours of refeeding. These variations were not observed in the obese rat. The regulation of NPY by the feeding state in the Zucker rat was therefore very different from that described in the SD rats. Strain or age of the animals used might explain these differences. High NPY levels and absence of regulation in obese Zucker rats could contribute to the abnormal feeding behavior of these rats.

Alteration of pituitary-adrenal responses to adrenalectomy by the immunological targeting of CRF neurons.

We previously demonstrated that cellular toxins added to a cytotoxic IgG2a monoclonal antibody to corticotropin releasing factor (CRF-MAb) may specifically penetrate some hypothalamic CRF neurons, after central injection near the paraventricular nuclei. We attempt here to evaluate the consequential effects on the CRF neurons functioning. Such a toxic mix, 4 weeks after its central injection, caused a marked reduction (66%) of the chronic adrenocorticotropic hormone (ACTH) release in response to a bilateral adrenalectomy (7th day). This change was accompanied by a reduction in the CRF concentration (43%) measured in the median eminence. We concluded that specific internalization of toxins, by the way of CRF-MAb, leads to a long-term dysregulation of the CRF synthesis and/or neuronal transport.

Diurnal rhythm of neuropeptide Y-like immunoreactivity in the suprachiasmatic, arcuate and paraventricular nuclei and other hypothalamic sites.

The diurnal rhythm of neuropeptide Y (NPY)-like immunoreactivity was examined in 9 discrete hypothalamic sites of rats maintained on a 12:12 h light/dark cycle. Significant bimodal rhythms of NPY concentration were detected in the suprachiasmatic and arcuate nuclei, with significant peaks just prior to onset of the nocturnal period and also at onset of the light period. In the parvocellular division of the paraventricular nucleus, a unimodal NPY peak was observed prior to dark onset. No diurnal rhythm was seen in the magnocellular division of the paraventricular nucleus, nor in 5 other hypothalamic areas examined.

Influence of diet composition on food intake and hypothalamic neuropeptide Y (NPY) in the rat.

Ingestion of a high carbohydrate (HC) or high fat (HF) diet induces obesity in association or not with modifications of the feeding behaviour. Effects of diet composition on NPY, a powerful stimulant of weight gain and food intake (particularly carbohydrates), are not known. That is why we measured NPY in 10 microdissected brain nuclei of rats fed either a HC diet (69% of energy from carbohydrates), a HF diet (68% of energy from fat) or a control well-balanced diet (54% of energy from carbohydrates; 30% of energy from fat) during a 14-day period. Total caloric intake was significantly greater (+12%) in rats fed on the HF diet than in the control and HC rats. HF rats also gained more weight than the two other groups (47.5 +/- 2.4 g vs 37.6 +/- 2.6 g (control) and 29.1 +/- 1.4 g (HC); p less than 0.001). NPY variations were restricted to two hypothalamic areas. In the parvocellular part of the paraventricular nucleus, NPY was smaller with the HC diet than with the HF diet (42.1 +/- 2.3 vs 49.5 +/- 2.7 ng/mg protein; p less than 0.05). A decrease was observed in the lateral hypothalamus with the HF diet when compared with the control diet (11.3 +/- 0.7 vs 14.6 +/- 1.1 ng/mg protein; p less than 0.05). No variations were observed either in other hypothalamic nuclei such as arcuate, dorsomedian, ventromedian or suprachiasmatic nuclei or in extra-hypothalamic areas such as the ventral tegmental area or submamillary bodies.(ABSTRACT TRUNCATED AT 250 WORDS)