Biomedical subjects

S F Leibowitz

Publications and source records attributed to S F Leibowitz.

175 records · Page 10Linked to original sources

PubMedDate not supplied

Endorphinergic and alpha-noradrenergic systems in the paraventricular nucleus: effects on eating behavior.

Brain cannulated rats were injected with the opioid peptide beta-endorphin (beta-EP) directly into the hypothalamic paraventricular nucleus (PVN) where norepinephrine (NE) is most effective in stimulating eating behavior. Beta-Endorphin (1.0 nmole) reliably increased food intake in satiated animals, and this response was blocked by local administration of the selective opiate antagonist naloxone. The eating induced by beta-EP was positively correlated in magnitude with the NE response and, like NE, was antagonized by PVN injection of the alpha-noradrenergic blocker phentolamine. Naloxone had no effect on NE-induced eating, and the dopaminergic blocker fluphenazine failed to alter either beta-EP or NE eating. When injected simultaneously, at maximally effective doses, beta-EP and NE produced an eating response which was significantly larger than either of the responses elicited separately by beta-EP or NE and was essentially equal to the sum of these two responses. The evidence obtained in this study suggests that beta-EP and NE stimulate food ingestion through their action on PVN opiate and alpha-noradrenergic receptors, respectively, and that beta-EP's action is closely related to, and in part may be dependent upon, the PVN alpha-noradrenergic system for feeding control.

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PubMedDate not supplied

Neurotensin: effects of hypothalamic and intravenous injections on eating and drinking in rats.

To investigate a role for the brain-gut peptide neurotensin (NT) in ingestive behavior, changes in food and water intake of food-deprived rats were examined following injection of NT into the paraventricular hypothalamic nucleus (PVN) or the mesenteric vein. Unilateral PVN NT (2.5, 5.0, 10.0 micrograms/0.3 microliter) produced substantial dose-dependent reductions in total food intake 0.5, 1, and 4 hr postinjection. In contrast, PVN NT had no effect on water intake and produced no change in grooming, rearing, sleeping, resting or locomotor activity. Bilateral PVN NT at a high dose (10.0 micrograms/side) suppressed consumption of solid or liquid diet in food-deprived rats, but did not affect water intake in water-deprived rats. This specificity is consistent with a role for CNS NT in feeding behavior. Intravenous NT (1-1000 pmole/kg/min for 30 min) did not specifically suppress food intake; however, low doses did increase water intake in food-deprived rats. These findings do not support a role for plasma NT in feeding, but do suggest that it may play a role in drinking behavior.

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PubMedDate not supplied

Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion.

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) is known to elicit a powerful feeding response in satiated, brain-cannulated rats. The present experiment investigates the effect of peptide YY (PYY), a structurally-related peptide, on feeding behavior and, in addition, the effects of both PYY and NPY on the pattern of macronutrient selection. Injection of PYY directly into the PVN, in doses ranging from 7.8 to 235 pmol/0.3 microliters, caused a strong, dose-dependent stimulation of feeding behavior, as well as a small stimulation of drinking behavior, in satiated rats. The mean latency to eat was 9.3 min, with substantial feeding occurring within 30 min of the injection. At low doses, the increase in feeding was seen predominantly during the first hr. At the highest dose, in contrast, food intake continued to increase progressively over the next few hr. such that by 4 hr postinjection food intake was more than 20 g over vehicle baseline. In 1 hr tests with 3 pure macronutrient (protein, fat and carbohydrate) diets simultaneously available, PYY and NPY (78 pmol/0.3 microliters) both elicited a strong and selective increase in carbohydrate consumption, with little or no effect on protein or fat consumption. These results suggest that hypothalamic receptors sensitive to PYY and NPY may participate in the control of carbohydrate consumption.

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PubMedDate not supplied

Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity.

Neuropeptide Y (NPY), a putative neurotransmitter abundant in the brain, has recently been shown to act within the hypothalamus, inducing a powerful eating response and a specific appetite for carbohydrates. In the present study, NPY (235 pmol) injected bilaterally in the paraventricular nucleus three times a day for 10 days caused approximately a two-fold increase in daily food intake, a six-fold increase in the rate of body weight gain and a three-fold increase in the body fat of female rats. Subsequently, the food intake and body weight of these subjects decreased precipitously, reaching control levels 20 days postinjection. These findings, demonstrating that exogenous NPY is capable of overriding mechanisms of satiety and body weight control, suggest that disturbances in NPY function may play a role in some disorders of eating behavior and body weight regulation.

Adipose Tissue↗

PubMedDate not supplied

Bombesin-induced anorexia: sites of action in the rat brain.

To determine the brain sites at which centrally injected bombesin (BBS) may act to suppress feeding behavior, this peptide (1.0 micrograms/0.3 microliter) was microinjected into one of twelve brain regions in 6 hr food deprived rats, and food intake was measured 45 min postinjection. Bombesin produced its strongest suppression of feeding (47-65%) when injected into hypothalamic areas, namely, the paraventricular, dorsomedial, ventromedial nuclei and lateral hypothalamus, and also when administered into the amygdala and the periaqueductal gray. Insensitive areas included the septum, ventral tegmental area and reticular formation. In contrast to these somewhat site-specific effects on feeding behavior, observation of BBS' effects on other behaviors revealed that, in all brain areas tested, there was a significant increase in grooming behavior and decrease in time spent resting and sleeping. In conjunction with high levels of BBS-like immunoreactivity and BBS receptors in the brain areas where injected BBS suppresses feeding, these results suggest that the effects of centrally administered BBS on feeding behavior may be mediated by multiple hypothalamic and extra-hypothalamic brain regions.

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PubMedDate not supplied

Effects of PVN galanin on macronutrient selection.

The neuropeptide galanin (GAL), after injection into the hypothalamic paraventricular nucleus (PVN), elicited a potent feeding response. In satiated rats maintained on pure macronutrient diets (protein, carbohydrate and fat), PVN GAL injection was found to cause a preferential increase in the consumption of the fat diet, with a significantly smaller increase in carbohydrate intake and no change in protein ingestion. When the fat diet was removed, GAL's stimulatory effect on carbohydrate ingestion was reliably and selectively enhanced. These effects of GAL stand in contrast to those of neuropeptide Y (NPY), which is co-localized with NE in the PVN and which induced in these animals a strong and selective enhancement of carbohydrate intake after PVN injection. Similarly, PVN NE, known to act via alpha 2-noradrenergic receptors, induced feeding specifically of carbohydrate and, to a small extent, fat. These differential results demonstrate the specificity of the effects of the peptides (GAL and NPY) and NE on macronutrient selection, all of which can be repeatedly observed in the same group of animals and which appear to be unrelated to the rats' natural 24 hr baseline preferences. However, we did observe a strong positive correlation between NE- and GAL-induced carbohydrate intake. In light of this relationship and additional pharmacological evidence linking GAL- and NE-induced feeding, it is proposed that the effects of GAL on macronutrient selection may be mediated, at least in part, by the alpha 2-noradrenergic feeding system within the PVN.

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PubMedDate not supplied

Stimulation of feeding by galanin: anatomical localization and behavioral specificity of this peptide's effects in the brain.

The neuropeptide galanin (GAL) has been found to elicit eating after injection into the hypothalamic paraventricular nucleus (PVN). To determine whether GAL's effect in the brain is anatomically specific, this peptide (0.1 or 0.3 nmol) was microinjected into one of 14 different brain areas of rats, and its impact on subsequent food intake was measured. Among the hypothalamic sites tested, only the PVN and the adjacent periventricular region yielded a significant eating response to GAL. With injection into the PVN, a feeding response was observed without apparent changes in other food-associated behaviors, e.g., drinking, grooming, resting and sleeping, or low and high levels of activity. All other hypothalamic and extrahypothalamic sites tested were unresponsive to GAL, with the exception of the amygdala where a significant eating response was observed. These findings suggest that central GAL elicits feeding by acting in an anatomically localized and behaviorally specific manner. In light of other pharmacological and anatomical evidence, it is suggested the PVN GAL, in modulating feeding behavior, may work in association with the catecholamine norepinephrine (NE) which is known to coexist with GAL in PVN neurons.

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PubMedDate not supplied

Analysis of neuropeptide Y-induced feeding: dissociation of Y1 and Y2 receptor effects on natural meal patterns.

To differentiate NPY receptor subtypes, Y1 and Y2, in terms of their impact on feeding behavior, the intact molecule NPY(1-36) and the 3 fragments, NPY(2-36), the Y1 agonist [Leu31,Pro34]NPY, and the Y2 agonist NPY(13-36), were injected (100 pmol/0.3 microliters) into the hypothalamic paraventricular nucleus (PVN) of freely feeding rats. A computer-automated data acquisition system was employed in these experiments to permit a detailed analysis of feeding over the 12-h nocturnal cycle, in animals maintained on pure macronutrient diets. The results demonstrate that: 1) NPY(1-36) potentiates feeding behavior, primarily carbohydrate ingestion, by increasing the size and duration of the first meal after injection, rather than by affecting meal number of feeding rate, suggesting that NPY acts through mechanisms of satiety. The potentiation of carbohydrate intake occurs in association with a suppression of protein intake, which is strongest during the second meal after injection and which further increases the proportion of carbohydrate in the diet. No changes in fat ingestion are seen. 2) NPY(2-36), with the N-terminal tyrosine residue deleted, is equally potent to NPY(1-36) in potentiating carbohydrate intake and increasing meal size; however, it is less selective than NPY(1-36), producing an additional, smaller increase in consumption of protein. 3) The stimulatory effect of these peptides on carbohydrate intake and meal size is similarly observed, with somewhat reduced potency, after PVN injection of the selective Y1 agonist [Leu31,Pro34]NPY which, like NPY(1-36), also reduces protein intake. 4) The Y2 receptor agonist, NPY(13-36), causes a decrease in the ingestion of carbohydrate, a smaller decline in protein intake, and a reduction in meal size. It is proposed that hypothalamic Y1 receptors mediate the stimulatory effect of NPY on carbohydrate intake and meal size, while Y2 receptors have the opposite effect of suppressing carbohydrate intake, possibly by altering presynaptic release of monoamines known to influence nutrient ingestion.

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PubMedDate not supplied

Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect.

Neuropeptide Y (NPY) elicits eating when injected directly into the paraventricular nucleus (PVN) or perifornical hypothalamus (PFH). To identify the essential regions of the NPY molecule and the relative contributions of Y1 and Y2 receptors, the eating stimulatory potency of NPY was compared to that of its fragments, analogues, and agonists when injected into the PVN or PFH of satiated rats. Additionally, antisera to NPY was injected into the cerebral ventricles (ICV) to determine whether passive immunization suppresses the eating produced by mild food deprivation. Tests with NPY fragments revealed that NPY(2-36) was surprisingly potent, nearly three times more so than intact NPY. In contrast, fragments with further N-terminal deletions were progressively less effective or ineffective, as was the free acid form of NPY. Collectively, this suggests that both N- and C-terminal regions of NPY participate in the stimulation of eating. Tests with agonists revealed that the putative Y1 agonist [Pro34]NPY elicited a strong dose-dependent feeding response, while the putative Y2 agonist, C2-NPY, had only a small effect at the highest doses. Although this suggests mediation by Y1 receptors, the uncharacteristically high potency of NPY(2-36) may additionally suggest that the receptor subtype underlying feeding is distinct from that mediating other responses. Additional results revealed that ICV injection of antisera to NPY, which should inactivate endogenous NPY, produced a concentration-dependent suppression of eating induced by mild food deprivation. This finding, along with published work demonstrating enhanced levels of hypothalamic NPY in food-deprived rats, suggests that endogenous NPY mediates the eating produced by deprivation.

Amino Acid Sequence↗

PubMedDate not supplied

Metabolic effects of galanin injections into the paraventricular nucleus of the hypothalamus.

The metabolic effects of single injections of galanin into the paraventricular nucleus of the hypothalamus (PVN) were investigated in an open-circuit calorimeter. Wistar rats were tested, with no food available during the tests. In the dose range of 0.03-0.3 nmol, galanin produced a very short-latency (approximately 2 minutes) and short-lasting (approximately 15 minutes) reduction in energy expenditure. Since the same doses had no effect on respiratory quotient or locomotor activity, the metabolic effect is not secondary to changes in energy substrate utilization or locomotor activity. This antithermogenic effect complements the eating stimulatory action of PVN galanin, and together these phenomena suggest a role for galanin as an anabolic neuropeptide. The similarity of galanin's effects to those of norepinephrine, with which it coexists in PVN nerve endings, further suggests the involvement of this amine and the PVN alpha2-noradrenergic system in galanin's mechanism of action.

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PubMedDate not supplied

Adrenergic stimulation of the paraventricular nucleus and its effects on ingestive behavior as a function of drug dose and time of injection in the light-dark cycle.

The paraventricular nucleus (PVN) has been identified as the most responsive site in the brain for eliciting feeding and preprandial drinking responses with local injection of norepinephrine (NE) in satiated rats. The present study examined these phenomena as a function of dose and time of injection in the light-dark cycle. The lowest effective doses for producing these ingestive responses with exogenous NE in the PVN are found to be between 5.6 and 16.9 ng for preprandial drinking and between 1.0 and 4.2 ng for feeding. Tests with NE injection into the PVN at different times in the light-dark cycle indicate that an increase in feeding effect can occur in the dark as well as in the light and at varying levels of food intake baseline and with solid and liquid food. Site of injection in the brain is believed to be a crucial factor in determining the nature of NE's effects on feeding behavior.

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PubMedDate not supplied

Brain neuropeptide Y: an integrator of endocrine, metabolic and behavioral processes.

Neuropeptide Y (NPY), acting through various medial hypothalamic nuclei, is found to have potent effects on a variety of endocrine, physiological and behavioral systems that modulate energy balance. This peptide affects the release of various hormones, such as corticosterone, insulin, aldosterone and vasopressin, which modulate energy metabolism, as well as food intake. It also has direct impact on energy metabolism through an effect on substrate utilization and lipogenesis. Finally, NPY has a remarkably potent stimulatory effect on feeding behavior, which is characterized by a selective increase in carbohydrate ingestion that is strongest at the beginning of the active feeding cycle and is dependent upon circulating levels of corticosterone. This evidence has led to the proposal that NPY exerts anabolic effects to restore energy balance at specific times of energy depletion. Increased NPY activity may occur at the beginning of the active cycle or after a period of food deprivation. Further evidence, that chronic NPY stimulation produces profound hyperphagia and obesity and that endogenous NPY concentration is increased in genetically obese animals, strongly suggests that hypothalamic NPY may contribute to the development of eating disorders and obesity.

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PubMedDate not supplied

Brain neurotransmitters and eating behavior in the elderly.

Based on published evidence, it is reasonable to propose that disturbances in brain neurotransmitters may contribute to the development of eating disorders in the elderly. The precise nature of these disturbances, however, cannot be defined until further studies are performed in aged animals and more careful attention is given to the specific brain site involved and the exact nature of the neurochemical change.

Aged↗