Spontaneous Food Intake Research Articles

Glucagon-like peptide-1: a potent regulator of food intake in humans

Background/AimsStudies in animals suggest a physiological role for glucagon-like peptide-1-(7–36)-amide (GLP-1) in regulating satiety. The role of GLP-1 in regulating food intake in man has, however, not been investigated.Subjects—Sixteen healthy...

Central administration of Y5 receptor antisense decreases spontaneous food intake and attenuates feeding in response to exogenous neuropeptide Y.

A number of neuropeptide Y (NPY) receptor subtypes, including the recently cloned Y5 receptor, have been implicated in the stimulation of food intake. In the present study, Y5 receptor antisense oligodeoxynucleotides (ODNs) were used to assess the potential involvement of the Y5 receptor in the regulation of spontaneous as well as NPY-induced food intake. Repeated central administration of Y5 antisense ODN significantly decreased spontaneous food intake and subsequently resulted in a significant weight loss. Furthermore, Y5 antisense ODN pre-treatment significantly inhibited the robust feeding response elicited by central administration of NPY (5.3+/-0. 8 vs 1.08+/-0.28 g, vehicle+/-s.e.m. vs Y5 ODN+/-s.e.m.). The present results provide evidence that central Y5 receptors are involved in both spontaneous as well as NPY-induced food intake, which may prove to be a new therapeutic route in the treatment of obesity and other disorders of appetite.

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.

Evidence That Orexigenic Effects of Melanocortin 4 Receptor Antagonist HS014 Are Mediated by Neuropeptide Y

Recent studies using melanocortin-4 receptor (MC4R) knockout mice and MC4R antagonists have shown that weakening of MC4R-ergic tone increases food intake and causes obesity. In this study, we used the newly discovered selective MC4R antagonist HS014 for increasing food intake in free-feeding rats and evaluated the effects of the NPY Y1receptor antagonist 1229U91 and the selective serotonin uptake inhibitor fluoxetine on this increased feeding behavior. 1229U91 (12 nmol, i.c.v.), which alone does not affect food intake, significantly attenuated the orexigenic effects of HS014, whereas 1 and 3 nmol doses of 1229U91 were ineffective. Fluoxetine, which has been shown to inhibit NPY release, inhibited spontaneous food intake and completely blocked the stimulation of food intake by HS014. These data suggest that feeding induced by weakening of the MC4R-ergic tone may be mediated through activation of the NPY-ergic system. This is the first report showing that physiological feeding response evoked by MC4R blockage is influenced by NPY signalling.

Effects of 14 d of covert substitution of olestra for conventional fat on spontaneous food intake

We conducted a double-blind, placebo-controlled, within-subject crossover study to investigate the effects of covert substitution of olestra, a non-energy-containing fat replacer, for conventional fat on food selection and energy intake in lean and obese men and women. Fifty-one subjects [BMI (kg/m2): 19-36; age: 25-63 y] were studied during two 14-d treatment periods (olestra and placebo), with a 7-d washout between feeding periods. During the intervention periods all foods were provided to the subjects. The aim was to produce a 10% dilution of total energy intake by replacing conventional triacylglycerol with olestra. To accomplish this, subjects were required to consume core foods providing 20-35 g olestra (depending on estimated energy needs) or the same foods containing placebo triacylglycerol. Additional items could be selected from foods that varied in macronutrient composition. When the two treatment periods were compared, total energy intake was 8% lower and fat intake 11% lower during the olestra period than during the placebo treatment period (P < 0.0001). Overall, subjects compensated for 15% of the fat and 20% of the total energy replaced by olestra. In absolute terms, subjects consumed 32% of total energy from fat during the placebo period and 27% of total energy from fat during the olestra period. Neither carbohydrate nor protein intake (g/d) differed between periods. The results did not differ as a function of BMI (lean compared with obese) or sex. Over a 2-wk period, covert substitution of olestra for conventional fat led to reductions in dietary fat intake and total energy intake in all subjects.

A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats.

Neuropeptide Y (NPY) is one of the most potent orexigenic substances known. 1229U91 was found to be a potent and selective NPY antagonist. To elucidate a physiological role of NPY in hyperphagia in obese animals, we studied the effect of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food intake of Zucker rats was suppressed by intracerebroventricular administration of 1229U91 more potently in obese than in lean animals without abnormal behavior (31.7 and 67.3% inhibition at doses of 10 and 30 micrograms, respectively, in Zucker fatty rats and 22.2% inhibition at 30 micrograms in lean rats). This compound markedly suppressed NPY-induced food intake at 30 micrograms but did not affect galanin-induced food intake, suggesting that the feeding suppression seen in Zucker fatty and lean rats is pharmacologically and behaviorally specific. These results suggest that NPY is involved in feeding behavior in Zucker fatty rats and that NPY contributes to feeding to a greater degree in Zucker fatty than in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal overactivation of the NPYergic system.

Prior Day’s Intake Has Macronutrient-Specific Delayed Negative Feedback Effects on the Spontaneous Food Intake of Free-Living Humans , ,

A fundamental issue in understanding how energy balance is accomplished involves comprehending how changes in intake affect subsequent intake. This was investigated in free-living humans by reanalyzing the data previously collected from 733 adults who were paid to maintain a 7-d diary of everything they ate and when they ate it. Food energy intake during a day was found to only mildly affect intake on the subsequent day (mean r = −0.07, P < 0.001), but was more strongly negatively related to intake occurring on the second (mean r = −0.18, P < 0.001) and third day (mean r = −0.10, P < 0.001) afterward. Each macronutrient was shown to have a maximal negative relationship with subsequent intake of that same macronutrient, with 2-d lag mean autocorrelations equal to −0.11, P < 0.001 for carbohydrate, equal to −0.18, P < 0.001 for fat, and equal to −0.13, P < 0.001 for protein. These effects on daily intake were found to result from separate negative feedback effects on meal size and frequency. The results suggest that intake affects subsequent intake by persistently setting a long-term bias that, integrated over time, produces a net shift in intake. J. Nutr. 128:61–67, 1998.

Effect of naltrexone on weight gain and food craving induced by tricyclic antidepressants and lithium: An open study

An unwanted increase in body weight frequently occurs during treatment with tricyclic antidepressants (TCAs) and lithium (Garland et al 1988; Baptista et al 1995), which is often accompanied by continuous hunger or episodes of craving for sweet and fatty food (Fernstrom and Kupfer 1988). A considerable number of patients discontinue drug treatment because of these side effects (Garland et al 1988). Appetite regulation is under opioidergic control, as acute administration of exogenous opiates to human volunteers increases spontaneous food intake (Levine and Billington 1989), and pleasantness ratings of ingested sucrose solutions (Drewnowski et al 1992). Conversely, acute blockade of opiate receptors results in decreased food ingestion (Levine and Billington 1989), especially of highly palatable food, decreases pleasantness ratings of palatable foodstuffs (Drewnowski et al 1992; Yeomans and Wright 1991), and diminishes subjective feeling of hunger (Bertino et al 1991). Chronic opiate receptor blockade using high dosages of naltrexone can effectively reduce frequency and severity of binge eating in bulimic patients (Jonas and Gold 1987). Opioid peptidergic function might be modulated by TCAs,

Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat.

Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food intake in rodents. To elucidate the mechanisms for these effects, we studied the hypothalamic content, synthesis, and distribution of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar rats, three weeks of zinc-deprivation consistently induced a reduction and a cyclic pattern of night- and day-time food intake, as well as of water intake. This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair-fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100 +/- 8, ZD: 61 +/- 4, PF: 78 +/- 2 arbitrary densitometric units, ADU, P < 0.01) and an increase of hypothalamic NPY (CTR: 100 +/- 11, ZD: 154 +/- 10, PF: 126 +/- 4 ADU, P < 0.05), without peptide modification. The two neuropeptidergic systems were not affected by the cycles of feeding, with the exception of the NPY-immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract), that was inversely correlated to the food intake in both ZD and PF animals. In a second experiment, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY synthesis was observed in ZD rats, suggesting that the increase observed in Wistar is adaptative rather than instrumental to the abnormal food intake. In conclusion, we have further characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and shown in these animals a decreased activity of the GAL system and an increased activity of the NPY system, likely corresponding to a compensatory response of the two neuropeptidergic systems, as observed in food-deprived animals. As spontaneous food intake of ZD rats does not increase, a resistance to NPY could also be present. These behavioural and neuropeptidergic changes were partially reversed by reintroduction of zinc in the diet. In Zucker rats, the same behaviour occurred despite an insensitivity of the NPY system to the zinc-deficiency. In addition, we describe a nutritional regulation of the NPY-immunoreactivity in the geniculo-hypothalamic tract, that could constitute the substrate of circadian rhythm modulation by timed feeding.

Behavioral, endocrine, and hypothalamic responses to involuntary overfeeding.

The suppression of food intake after a period of forced overfeeding is potent and long lasting, yet little is known of the underlying mechanisms for this regulatory response. Rats were overfed via a surgically implanted gastrostomy tube. During overfeeding, plasma insulin and corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus were elevated compared with controls and with overfed rats allowed 3 days to recover from the overfeeding regimen such that body weight returned to the level of controls. In contrast, rats that were not overfed but were pair-fed to the low spontaneous food intake of previously overfed rats lost weight and had significantly reduced plasma insulin and elevated mRNA for neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus. The results indicate that overfeeding produces an activation of hypothalamic CRH system that may contribute to the hypophagia that accompanies involuntary overfeeding. Furthermore, the hypothalamic NPY response to food restriction is not tied to low food intake per se, but rather to negative energy balance.

Mode of food intake reduction in Lewis rats with indomethacin-induced ulcerative ileitis

The mechanism of anorexia in inflammatory bowel disease is poorly understood. To gain insight into possible pathophysiologic mechanisms, the feeding indices and food intake were studied in an animal model of Crohn's disease. The anorexia of indomethacin-induced ulcerative ileitis was compared with that of the well-known anorexia of total parenteral nutrition (TPN). Forty-five female Lewis rats were randomized to four groups: Control, Indomethacin, Indomethacin + TPN, and TPN. Feeding indices and food intake were continuously measured using the Automated Computerized Rat Eater Meter. Interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), prostaglandin E 2 (PGE 2), and leukotriene B 4 (LTB 4) were assayed in plasma, mononuclear cell culture, or ileum to determine their role in mediating anorexia. In the TPN group, spontaneous food intake (SFI) decreased (52%; p < 0.05), primarily via reduction in meal number (MN, 54%; p < 0.05) and, to a lesser extent, meal size (MZ, 35%; p < 0.05). In comparison, in the Indomethacin group SFI decreased (74%; p < 0.05) primarily via reduction in MZ (67%, p < 0.05); MN also decreased but to a lesser extent (27%; p < 0.05). In the Indomethacin + TPN group, SFI decreased (55%; p > 0.05) primarily via reduction in MN (79%; p < 0.05), whereas MZ decreased slightly (19%; p < 0.05). Only in the Indomethacin group were IL-1α and TNF-α detected in the mononuclear cell culture and plasma, respectively. In the Indomethacin group, an inverse correlation existed between MZ and TNF-α ( p < 0.05). In the Indomethacin group, IL-1α, PGE 2, and LTB 4 concentrations did not correlate with feeding indices. SFI reduction in this model was mediated primarily via a decrease in MZ. TNF-α is proposed to mediate this effect and TPN was shown to overcome the effect on MZ.

Antisense oligodeoxynucleotides against the MOR-1 clone alter weight and ingestive responses in rats

MOR-I encodes a μ receptor. In an effort to establish the relationship of this cloned opioid receptor with ingestive behavior and analgesia in rats, the present study examined the actions of four antisense oligodeoxynucleotides aimed at exons I (AS 1), 2 (AS2), 3 (AS3) and 4 (AS4) of the MOR-1 clone, as well as a mismatch antisense sequence WS 1). Rats were administered intracerebroventricular injections (10 μg/2 μl) of each of the oligodeoxynucleotides on days 1, 3 and 5. Body weight and spontaneous food and water intake were monitored daily. In addition, 2-deoxy-D-glucose (213G)-induced hyperphagia, central Angiotensin II (ANG-II)-induced hyperdipsia and central morphine analgesia were examined 24 h following the last antisense injection. ASI, AS2, AS3 and AS4 each significantly reduced body weight (7–17 g), food intake (8–13 g) and water intake (11–23 ml), while the vehicle or MS1 conditions significantly increased weight (9–20 g) and produced smaller reductions (2–4 g) in food intake. None of the AS probes altered the magnitude of either 2DG-induced hyperphagia or ANG-II-induced hyperdipsia. Central morphine analgesia was reduced by pretreatment with AS 1 and AS4, but not AS2, AS3 or MS1. The sensitivity of general feeding to all four exons suggest that the receptor responsible for this action is encoded by the MOR-1 clone. The differences between feeding and morphine analgesia raise the possibility that these two actions are mediated through different μ receptor subtypes. Our results also demonstrate the viability of the in vivo antisense technique in modulating opioid-mediated ingestive responses.

The gut-brain brain-gut axis in anorexia: Toward an understanding of food intake regulation

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes—thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

The gut-brain brain-gut axis in anorexia: toward an understanding of food intake regulation.

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes--thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

General, μ and κ opioid antagonists in the nucleus accumbens alter food intake under deprivation, glucoprivic and palatable conditions

Ventricular microinjection studies found that whereas μ (β-funaltrexamine, B-FNA), μ 1 (naloxonazine) and κ (nor-binaltorphamine, Nor-BNI) opioid receptor antagonists, but not δ antagonists, reduce deprivation-induced intake, κ and μ, but not μ 1 or δ antagonists reduce both 2-deoxy- d-glucose (2DG) hyperphagia and sucrose intake. Since opioid agonists stimulate spontaneous food intake in the accumbens, the present study examined whether administration of either naltrexone, B-FNA or Nor-BNI in the accumbens altered intake under deprivation (24 h), glucoprivic (2DG: 500 mg/kg, i.p.) or palatable sucrose (10%) conditions. Naloxonazine's effects in the accumbens were also evaluated for deprivation-induced intake. Deprivation-induced intake was significantly decreased over 4 h by naltrexone (5–20 μg, 44%), B-FNA (1–4 μg, 55%) and Nor-BNI (4 μg, 31%), but not naloxonazine (10 μg) in the accumbens. 2DG hyperphagia was significantly decreased by naltrexone (10–20 μg, 79%), B-FNA (1–4 μg, 100%) and Nor-BNI (1–4 μg, 75%) in the accumbens. Sucrose intake was significantly decreased by naltrexone (50 μg, 27%) and B-FNA (1–4 μg, 37%), but not Nor-BNI in the accumbens. These data suggest that μ receptors, and particularly the μ 2 binding site in the accumbens are responsile for the opioid modulation of these forms of intake in this nucleus, and that this control may be acting upon the amount of intake per se.

Effects of different types of isocaloric parenteral nutrients on food intake and metabolic concomitants

Whether spontaneous food intake (SFI) is controlled by infused nutrient type or its caloric content, irrespective of nutrient type, was investigated. Rats were infused for 4 days with isocaloric solutions of different nutrient type but sharing the same intermediary metabolic oxidative pathway, providing 25% of daily caloric needs. One parenteral solution was a glucose, fat and amino acid mix (TPN-25%); the other provided ketone bodies (TRO-3.5%). Effects of parenteral infusions on SFI and metabolic concomitants were compared and contrasted to that in a group of orally fed rats. Both infusions reduced SFI by 50%. Rats receiving TRI-3.5% had lower blood glucose and insulin concentrations, but increased hepatic glycogen content compared to TPN-25% or orally fed rats. No differences in hepatic triglycerides occurred between the three groups. However, serum free fatty acids were significantly lower in TRI-3.5% and in TPN-25% groups vs. fed rats. Data indicate food intake suppression is mediated by caloric content rather than nutrient type, suggesting that a mediator of SFI regulation could be at the citric acid cycle level.

Effect of a covert fat dilution on the spontaneous food intake by lean and obese subjects

Nine lean and nine obese subjects participated in two laboratory studies comparing the effects of a traditional high-fat dish (2.42 MJ and 49% as fat) and its convert fat-reduced version (1.53 MJ and 23% as fat) on subsequent food intake. Each version was consumed at the beginning of a free-choice lunch (experiment 1) or alone at lunch time (experiment 2). All subjects experienced both experiments. Three and 7 h after lunch, subjects were free to consume any of the items available in a vending machine. Food intake was measured directly. In experiment 1, by 8 h after lunch, mean cumulative energy intake (test dish included) was not different between the test dish conditions in both lean and obese subjects, and ad libitum energy intake (i.e. without test dish) was significantly higher under the low-fat than under the high-fat test dish condition. Thus, lean compensated 86% and obese 70% of the initial energy reduction. The cumulative fat intake (test dish included) was lower under the low-fat than under the high-fat dish condition for both weight groups. Nevertheless, the percentage of ad libitum energy intake derived from fat was significantly higher after the low-fat test dish in obese but not in lean subjects. In experiment 2, both weight groups maintained the energy and fat reduction. Thus, obese subjects did not respond differently to lean subjects to the fat and energy manipulation of the test dish, except for the percentage of fat in their diet. These results suggest that different ways of including fat-reduced foods into the habitual diet might have different effects on subsequent energy compensation.

The relationship of cognitive restraint to the spontaneous food and fluid intake of free-living humans

How the desire to restrain intake, cognitive restraint, may influence the amount or pattern of food and fluid intake was investigated by studying the spontaneous intake of free-living humans. The Three-Factor Eating Questionnaire and the Restraint Scale were completed by 358 adults who also were paid to maintain 7-day diaries of their intake. For both males and females, higher cognitive restraint was associated with lower and less variable overall intake, especially of fat and carbohydrate. This resulted from the ingestion of smaller and less variable meals that contained less fat. In addition, high restraint was associated with smaller deprivation ratios, and lower estimated before and after meal stomach contents. Although females were higher in restraint than males, comparable levels of restraint had equivalent effects upon intake. The results suggest that restrained subjects simply eat less because they require less with cognitive restraint as a secondary consequence.

Influence of antibiotics and food intake on liver glutathione and cytochrome P-450 in septic rats

The present experiment was undertaken to verify if the demand of tissues for pteroylglutamic (folic) acid, evaluated by serum clearance and urinary excretion of folates, is different between multiparous dairy cows in late gestation (five gestating dry cows, 52.6 (SD 8.4) d before parturition), and in early lactation (four lactating non-gestating cows, 18.0 (SD 5.9) d after parturition). On day 1 the cows received one intravenous (i.v.) injection of 50 micrograms pteroylmonoglutamic acid/kg body weight (BW). Blood samples were taken at 0, 5, 15, 30 min, 1, 2, 4, 8 and 24 h after the i.v. injection. On day 3 the cows received one intramuscular (i.m.) injection of 0.3 mg pteroylmonoglutamic acid/kg BW. Blood and urine samples, as well as urine volume, were taken at 0, 1, 2, 4, 8, 12, 24, 36 and 48 h after the i.m. injection. On days 5, 6 and 7 a daily i.m. injection of 0.5 mg pteroylmonoglutamic acid/kg BW was given in an attempt to saturate tissues with folates. Then the cows received one i.v. (day 8) and one i.m. (day 10) injection of pteroylmonoglutamic acid according to the same procedures described previously for days 1 and 3. On day 12 plasma volume was determined. Before tissue saturation, serum clearance of folates during the 24 h following an i.v. injection was similar for gestating and lactating cows but after tissue saturation serum clearance was slower for lactating than gestating cows (stage x saturation, P = 0.04). The percentage of folates excreted in urine was not affected by the physiological stage (P > or = 0.6) or the level of tissue saturation (P > or = 0.5). In conclusion, serum clearance and urinary excretion of pteroylmonoglutamic acid seem to support the hypothesis that, in multiparous cows, although there are no deficiency symptoms, tissue demand for folic acid is high, especially during gestation.

Putative neuropeptide Y antagonist failed to decrease overeating in obese Zucker rats

A central dysregulation of several neuropeptides could be at the origin of the marked hyperphagia of the obese Zucker rat, a well-known animal model used for the study of obesity. Neuropeptide Y (NPY), which stimulates food intake and increases early in life in obese rats, plays a major role in the development of this hyperphagia. The aim of our experiment was to test a proposed NPY antagonist namely PYX-2 in obese hyperphagic Zucker rats in order to know if it could be an interesting drug for limiting their food intakes. Four doses of PYX-2 (50–1000 pmol) were injected in a counterbalanced order in the lateral brain ventricles of 10 adult male Zucker rats. Food intake was recorded 0.5, 1, 2, 3, 6, and 23 h after PYX-2 injection and compared either to the rat's spontaneous food intake or to the food intake following injection of artificial CSF (vehicle) only. It was not modified by any dose of PYX-2 whatever the time considered (1 h after injection: 4.3 ± 0.5 (1000 pmol) vs 4.6 ± 0.8 (CSF) g; 23 h period: 27.0 ± 1.9 (1000 pmol) vs 26.6 ± 2.9 (CSF) g; N.S.). Thus, PYX-2, the putative NPY antagonist, totally failed to inhibit food intake in the obese rats. The absence of effect of PYX-2 on food intake can be explained by the structure of PYX-2, a modified 27–36 amino acid sequence that may not be recognized by the Y 1-type NPY receptors which are involved in the regulation of feeding behavior.