RESUMEN
Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.
Asunto(s)
Depresores del Apetito/farmacología , Regulación del Apetito/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Péptido YY/farmacología , Animales , Animales Endogámicos , Apetito/efectos de los fármacos , Apetito/fisiología , Depresores del Apetito/uso terapéutico , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ambiente , Humanos , Metaanálisis como Asunto , Ratones , Obesidad/tratamiento farmacológico , Fragmentos de Péptidos , Péptido YY/administración & dosificación , Péptido YY/sangre , Péptido YY/uso terapéutico , Ratas , Reproducibilidad de los Resultados , Estrés Fisiológico/complicaciones , Estrés Fisiológico/fisiopatologíaRESUMEN
Little is known regarding satiety effects of systemically administered cholecystokinin (CCK-8) in propensity or resistance to dietary-induced obesity (DIO), and of its effect under conditions of melanocortin-3/4R blockade. We found that CCK-8 exerted greater satiety effects in DIO-prone but not DIO-resistant rats, and this occurred only when the rats were placed on a high-fat (HF) diet, when DIO-prone rats failed to compensate for the greater energy density of the diet. CCK-8 also suppressed intake stimulated by melanocortin-3/4R antagonist, SHU9119, but only after 24h of increased feeding. This suggests that under both of these conditions, responsiveness to CCK's satiety effect is not so much affected by a HF diet or significant increases in body weight per se, but by a failure to rapidly limit food intake to that needed only for metabolic need. Identification of an early feeding mediator that is most strongly activated by a HF diet or by an acute challenge to energy homeostasis should provide an ideal anti-obesity target adjunct to CCK-8.
Asunto(s)
Obesidad/metabolismo , Receptor de Melanocortina Tipo 3/metabolismo , Receptor de Melanocortina Tipo 4/metabolismo , Respuesta de Saciedad/efectos de los fármacos , Sincalida/farmacología , Animales , Dieta , Masculino , Hormonas Estimuladoras de los Melanocitos/farmacología , Obesidad/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Receptor de Melanocortina Tipo 3/antagonistas & inhibidores , Receptor de Melanocortina Tipo 4/antagonistas & inhibidoresRESUMEN
Dieting and stress are important in the etiology and maintenance of eating disorders, and dieting strongly predicts stress-induced overeating in humans. We hypothesized that caloric restriction and stress interact in a unique manner to promote binge eating. To test this hypothesis, a group of young female rats were cycled through a restriction period (4 days of 66% of control food intake) followed by 6 days of free feeding prior to being stressed by acute foot shock. After three of these cycles, the food intake of rats exposed only to restriction (R), or only to stress (S), did not differ from controls. However, R+S rats that were restricted and refed, despite normal body weight and food intake after free feeding, engaged in a powerful bout of hyperphagia when stressed (Experiment 1). The R + S effect was replicated in an older group of rats (Experiment 2). The hyperphagia was characteristically binge-like, it constituted a 40% selective increase in highly palatable (HP) food (P < .001) over a discrete period of time (within 24 h post-stress), and reflected feeding for reward (higher HP:chow ratio) over metabolic need as occurred after restriction (higher chow:HP ratio). Subsequent experiments revealed that binge eating did not occur if only chow was available (Experiment 3) or if restriction-refeeding (R-R) did not proximally precede stress (Experiment 4). Experiment 5 revealed that a history of R-R cycles followed by only one stress episode was sufficient to increase intake to 53% above controls as early as 2 h after stress (P < .001). This animal model of binge eating should facilitate investigations into the neurochemical changes induced by dieting and environmental stress to produce disordered eating and provide a preclinical tool to test preventive strategies and treatments more relevant to bulimia nervosa, multiple cases of binge eating disorder (BED) and binge-purge type anorexia nervosa.
Asunto(s)
Bulimia/etiología , Bulimia/fisiopatología , Privación de Alimentos/fisiología , Estrés Fisiológico/complicaciones , Animales , Modelos Animales de Enfermedad , Electrochoque , Ingestión de Energía , Femenino , Alimentos , Preferencias Alimentarias , Pie , Ratas , Ratas Sprague-Dawley , GustoRESUMEN
Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic beta cells in response to feeding. We recently reported that amylin potently reduces food intake, body weight, and adiposity when delivered into the 3rd cerebral ventricle (i3vt) of rats. We have now infused i3vt a specific antagonist (AC187) to ascertain the physiological relevance of central amylin in the control of energy balance. After establishing the ability of i3vt AC187 to block the anorexic effect of i3vt amylin, we performed an experiment to examine the impact of acute inhibition of central amylin signaling on feeding. Separate groups (n = 7/group) of ad lib-fed male Long Evans rats were given one bolus i3vt infusion of synthetic cerebrospinal fluid vehicle (CSF) or AC187 (250 or 1000 pmol). Acute infusion of AC187 tended to increase 1-h food intake and significantly elevated 4-h intake. Both the 250 and 1000 pmol doses produced significant increases as compared to CSF. In another experiment designed to tonically inhibit central amylin signaling over an extended period, two other groups of rats (n = 6/group) received continuous i3vt infusion of CSF or 100 pmol/h AC187 over 14 days via implantable osmotic pumps. Rats receiving AC187 ate significantly more food over the 14-day infusion period relative to controls (CSF = 322 +/- 6 g, AC187 = 360 +/- 12 g). Although body weight was not significantly affected, body fat was increased by about 30% in the AC187 rats, with no difference in lean tissue between the groups. Additionally, although fasting plasma glucose did not differ between the CSF and AC187 groups after 14 days of infusion, plasma insulin was significantly elevated in the AC187 rats. In summary, the present results document significant increases of food intake and body adiposity resulting from inhibition of central amylin signaling. They are consistent with our hypothesis that CNS actions of endogenous amylin contribute to the long-term regulation of energy balance.
Asunto(s)
Tejido Adiposo/anatomía & histología , Amiloide/antagonistas & inhibidores , Amiloide/fisiología , Composición Corporal/fisiología , Encéfalo/metabolismo , Ingestión de Alimentos/fisiología , Transducción de Señal/fisiología , Animales , Inyecciones Intraventriculares , Polipéptido Amiloide de los Islotes Pancreáticos , Masculino , Fragmentos de Péptidos , Péptidos/farmacología , Ratas , Ratas Long-Evans , Tercer Ventrículo , Factores de TiempoRESUMEN
Agouti-related peptide (AgRP) is a receptor antagonist of central nervous system (CNS) melanocortin receptors and appears to have an important role in the control of food intake since exogenous CNS administration in rats and overexpression in mice result in profound hyperphagia and weight gain. Given that AgRP is heavily colocalized with neuropeptide Y (NPY) and that orexigenic effects of NPY depend on activity at opioid receptors, we hypothesized that AgRP's food-intake effects are also mediated by opioid receptors. Subthreshold doses of the opioid receptor antagonist naloxone blocked AgRP-induced intake when given simultaneously but not 24 h after AgRP injection. Opioids not only influence food intake but food selection as well. Hence, we tested AgRP's effect to alter food choice between matched diets with differing dietary fat content. AgRP selectively enhanced intake of the high-fat but not the low-fat diet. Additionally, AgRP selectively increased chow intake in rats given ad libitum access to a 20% sucrose solution and standard rat chow. The current results indicate that AgRP influences not only caloric intake but food selection as well and that the early effects of AgRP depend critically on an interaction with opioid receptors.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Preferencias Alimentarias/efectos de los fármacos , Proteínas/farmacología , Receptores Opioides/fisiología , Proteína Relacionada con Agouti , Animales , Grasas de la Dieta/administración & dosificación , Sacarosa en la Dieta/administración & dosificación , Relación Dosis-Respuesta a Droga , Ingestión de Energía , Péptidos y Proteínas de Señalización Intercelular , Masculino , Naloxona/administración & dosificación , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Fragmentos de Péptidos/farmacología , Ratas , Ratas Long-Evans , SolucionesRESUMEN
Several lines of evidence substantiate the important role of the central nervous system melanocortin 3- and 4-receptor (MC3/4-R) system in the control of food intake and energy balance. Agouti-related peptide (AgRP), an endogenous antagonist of these receptors, produces a robust and unique pattern of increased food intake that lasts up to 7 days after a single injection. Little is known about brain regions that may mediate this powerful effect of AgRP on food intake. To this end we compared c-Fos-like immunoreactivity (c-FLI) in several brain sites of rats injected intracerebroventricularly with 1 nmol AgRP-(83--132) 2 and 24 h before death and compared c-FLI patterns to those induced by another potent orexigenic peptide, neuropeptide Y (NPY). Although both NPY and AgRP induced c-FLI in hypothalamic areas, AgRP also produced increased c-FLI in the accumbens shell and lateral septum. Although NPY elicited no changes in c-FLI 24 h after administration, AgRP induced c-FLI in the accumbens shell, nucleus of the solitary tract, central amygdala, and lateral hypothalamus. These results indicate that an NPY-like hypothalamic circuit mediates the short-term effects of AgRP, but that the unique sustained effect of AgRP on food intake involves a complex circuit of key extrahypothalamic reward and feeding regulatory nuclei.
Asunto(s)
Encéfalo/metabolismo , Fragmentos de Péptidos/farmacología , Proteínas Proto-Oncogénicas c-fos/fisiología , Proteína Relacionada con Agouti , Animales , Hipotálamo/metabolismo , Inmunohistoquímica , Inyecciones Intraventriculares , Masculino , Neuropéptido Y/farmacología , Ratas , Ratas Long-Evans , Factores de Tiempo , Distribución Tisular/efectos de los fármacosRESUMEN
Overexpression of agouti-related peptide (AgRP), an endogenous melanocortin (MC) 3 and 4 receptor antagonist (MC3/4-R), causes obesity. Exogenous AgRP-(83---132) increases food intake, but its duration and mode of action are unknown. We report herein that doses as low as 10 pmol can have a potent effect on food intake of rats over a 24-h period after intracerebroventricular injection. Additionally, a single third ventricular dose as low as 100 pmol in rats produces a robust increase in food intake that persists for an entire week. AgRP-(83---132) completely blocks the anorectic effect of MTII (MC3/4-R agonist), given simultaneously, consistent with a competitive antagonist action. However, when given 24 h prior to MTII, AgRP-(83---132) is ineffective at reversing the anorectic effects of the agonist. These results support a critical role of MC tone in limiting food intake and indicate that the orexigenic effects of AgRP-(83---132) are initially mediated by competitive antagonism at MC receptors but are sustained by alternate mechanisms.
Asunto(s)
Estimulantes del Apetito/farmacología , Ingestión de Alimentos/efectos de los fármacos , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Receptores de Corticotropina/antagonistas & inhibidores , Proteína Relacionada con Agouti , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Péptidos y Proteínas de Señalización Intercelular , Oligopéptidos/administración & dosificación , Oligopéptidos/antagonistas & inhibidores , Ratas , Ratas Long-Evans , Receptor de Melanocortina Tipo 3 , Receptor de Melanocortina Tipo 4 , Tiempo , alfa-MSH/análogos & derivadosRESUMEN
Studies using nonselective agonists and antagonists of melanocortin-3 receptor (MC3R) and MC4R point to the importance of the CNS melanocortin system in the control of food intake. We describe here a novel compound that is highly selective as an agonist at the MC4 receptor but has minimal activity at the MC3 receptor. When administered centrally to rats, this selective agonist increased Fos-like immunoreactivity in the paraventricular nucleus, central nucleus of the amygdala, nucleus of the solitary tract, and area postrema, a pattern of neuronal activation that is similar to that induced by a nonselective MC3/4R agonist. Additionally, it suppresses food intake when administered centrally to rats or peripherally to db/db mice that lack functional leptin receptors via a mechanism that is not accompanied by illness or other nonspecific effects. Conversely, a related compound that is a selective MC4R antagonist potently increased food intake when administered centrally in rats. These results support the hypothesis that the brain MC4R is intimately involved in the control of food intake and body weight and provide evidence that selective activation of MC4R causes anorexia that is not secondary to aversive effects.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Receptor de Melanocortina Tipo 4/agonistas , Animales , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Genes fos/efectos de los fármacos , Genes fos/fisiología , Masculino , Ratones , Ratones Obesos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Long-Evans , Receptor de Melanocortina Tipo 4/antagonistas & inhibidoresRESUMEN
Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic B cells in response to a nutrient stimulus (e.g., during meals). To test the hypothesis that amylin acts within the brain to reduce long-term food intake and body weight, we examined the effects of acute and chronic 3rd-ventricular (i3vt) infusion of low doses of amylin on food intake and body weight in rats. In one experiment, separate groups of ad lib-fed male Long Evans rats were given one i3vt infusion (3 microl over 30 s) of synthetic cerebrospinal fluid vehicle or 1 to 100 pmol amylin, and food intake and body weight were monitored for 7 days. Amylin potently and dose-dependently reduced 1-h food intake, with all doses producing significant reductions. The largest dose (100 pmol) significantly reduced 24-h intake by over 30%. The effect was persistent in that both 7-day cumulative food intake and body weight change were significantly decreased over the 7 days following a single injection of 100 pmol of amylin. Other groups of rats received continuous i3vt infusion (0.5 microl/h volume) of saline or 2.0 pmol/h amylin via osmotic minipumps over 10 days. Food intake over the 10-day infusion was significantly suppressed in amylin-treated rats as compared to that of controls. Consequently, by the 4th day of infusion, amylin rats weighed significantly less than baseline relative to saline controls, and this difference persisted throughout the remainder of the infusion period. At sacrifice (Day 10), the percent of body weight from retroperitoneal fat depots was significantly lower in the amylin-treated rats, indicative of a reduction of total body adiposity. In summary, the results support the hypothesis that amylin acts as a signal to the brain contributing to the maintenance of long-term energy balance.
Asunto(s)
Amiloide/farmacología , Encéfalo/fisiología , Ventrículos Cerebrales/fisiología , Conducta Alimentaria/efectos de los fármacos , Amiloide/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Ventrículos Cerebrales/efectos de los fármacos , Esquema de Medicación , Infusiones Parenterales , Polipéptido Amiloide de los Islotes Pancreáticos , Masculino , Ratas , Ratas Long-Evans , Factores de TiempoRESUMEN
Dieting and concern with weight were found to be associated with psychological and neurological symptoms observed in cases of severe semi-starvation. College students of both sexes (n 292) and high school females (n121) rated themselves on dietary restraint and psychological and physical symptoms that were prevalent in men after 24 weeks in the Minnesota semi-starvation experiment of 1944-5. Apprehension, irritability, and moodiness were associated with a high concern with restraint. Blank spells, hunger pain, concern for health, and social withdrawal were associated with a history of restraint. Depression, lower self-esteem, eating behavior patterns, apathy, and decreased motivation were associated with both restraint parameters. Our results suggest that normal dieting may be more closely related to psychological and health risks associated with chronic semi-starvation than is commonly believed.
RESUMEN
Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites, beta-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed.
Asunto(s)
Leptina/sangre , Leptina/líquido cefalorraquídeo , Adulto , Índice de Masa Corporal , Ritmo Circadiano , Dopamina/sangre , Dopamina/líquido cefalorraquídeo , Ayuno/sangre , Ayuno/líquido cefalorraquídeo , Humanos , Hidrocortisona/sangre , Hidrocortisona/líquido cefalorraquídeo , Hidrocortisona/orina , Masculino , Persona de Mediana Edad , Fumar , Trastornos por Estrés Postraumático/sangre , Trastornos por Estrés Postraumático/líquido cefalorraquídeo , Trastornos por Estrés Postraumático/orinaRESUMEN
The purpose of the present study was to evaluate methanesulfonyl fluoride (MSF), a very long-acting CNS-selective acetylcholinesterase (AChE) inhibitor, as a palliative treatment for senile dementia of the Alzheimer type (SDAT). In experiment I, MSF (0.03-0.18 mg/kg) was administered orally to 10 normal volunteers to measure toxicity and establish dose/response function in erythrocyte AChE. MSF produced a dose-response function of %inhibition = (40)(Log10[MSF mg/kg] + 51.7) with no toxicity at these doses. Experiment II was a 16-week double-blind, placebo-controlled study of the safety and efficacy of MSF in doses of up to 0.18 mg/kg given three times per week in 5 men and 10 women (60-82 years), with Mini-Mental State Examination (MMSE) scores of 9-24, who had SDAT. MSF produced a mean of 89.5% inhibition of erythrocyte AChE in patients and improved cognitive performance as measured by the MMSE, Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-COG), Global Deterioration Scale, and the Clinical Interview Based Impression of Change (CIBIC). Most of the improvement on the ADAS-COG was maintained 8 weeks after ending MSF. No patients left the study because of drug-related adverse events and there were no toxic effects. MSF may be a safe and effective palliative treatment for SDAT and further clinical trials in larger groups of patients are warranted.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Demencia/tratamiento farmacológico , Sulfonas/uso terapéutico , Acetilcolinesterasa/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Administración Oral , Adulto , Enfermedad de Alzheimer/patología , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/farmacología , Cognición/efectos de los fármacos , Demencia/patología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Sulfonas/administración & dosificación , Sulfonas/farmacología , Resultado del TratamientoRESUMEN
The voluntary suppression of food intake that accompanies involuntary overfeeding is an effective regulatory response to positive energy balance. Because the pro-opiomelanocortin (POMC)-derived melanocortin system in the hypothalamus promotes anorexia and weight loss and is an important mediator of energy regulation, we hypothesized that it may contribute to the hypophagic response to overfeeding. Two groups of rats were overfed to 105 and 116% of control body weight via a gastric catheter. In the first group, in situ hybridization was used to measure POMC gene expression in the rostral arcuate (ARC). Overfeeding increased POMC mRNA in the ARC by 180% relative to levels in control rats. For rats in the second group, the overfeeding was stopped, and they were infused intracerebroventricularly with SHU9119 (SHU), a melanocortin (MC) antagonist at the MC3 and MC4 receptor, or vehicle. Although SHU (0.1 nmol) had no effect on food intake of control rats, intake of overfed rats increased by 265% relative to CSF-treated controls. This complete reversal of regulatory hypophagia not only maintained but actually increased the already elevated weight of overfed rats, whereas CSF-treated overfed rats lost weight. These results indicate that CNS MCs mediate hypophagic signaling in response to involuntary overfeeding and support the hypothesis that MCs are important in the central control of energy homeostasis.
Asunto(s)
Encéfalo/metabolismo , Hiperfagia/metabolismo , alfa-MSH/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Hiperfagia/fisiopatología , Hibridación in Situ , Masculino , Hormonas Estimuladoras de los Melanocitos/farmacología , Concentración Osmolar , Proopiomelanocortina/genética , ARN Mensajero/metabolismo , Ratas , Ratas Long-EvansRESUMEN
Binge eating is a consequence of semistarvation in victims of war and famine and in volunteers in rare semistarvation experiments. These behaviors include bizarre mixing of ingredients and adulteration of food; eating inappropriate, soiled, or discarded food; secrecy; deception; and defensiveness. Drastic measures to resist overeating persist long after the semistarvation experience, even when food is plentiful. Binge eating, a central feature of bulimia and sometimes of anorexia nervosa, is prevalent in modern society, but the occurrence and frequency of semistarvation-related behaviors have not been well identified or quantified. A Semistarvation-Associated Behaviors Scale was constructed and administered to 40 college students. Among binge eaters, reports of bizarre semistarvation-like behaviors were common and frequent and were associated with dieting.
Asunto(s)
Bulimia/psicología , Conducta Alimentaria , Hiperfagia/psicología , Inanición/psicología , Adolescente , Adulto , Anorexia Nerviosa/diagnóstico , Anorexia Nerviosa/psicología , Bulimia/diagnóstico , Dieta Reductora/psicología , Conducta Alimentaria/psicología , Femenino , Humanos , Hiperfagia/diagnóstico , Masculino , Persona de Mediana Edad , Estudiantes/psicologíaRESUMEN
Central injection of peptide YY (PYY) in sated rats produces the most powerful stimulating effect of food intake known to date. The neural mechanisms by which PYY regulates appetite are not clear but may be important because abnormal levels of PYY have been implicated in the neurobiology of bulimia nervosa. Interactions between brain acetylcholine (ACh) and PYY had not been studied. Therefore, the present experiments were designed to explore the in vivo release of ACh from the hippocampus (HPC) of rats in response to hypothalamic infusion of PYY. Hippocampal ACh release was found to increase 400% in response to 10 microg PYY. In a separate experiment, blockade of the same area of the HPC with bilateral intracerebral injections of 3.5 microg scopolamine did not affect intake stimulated by intrahypothalamic injection of 4 microg PYY. Furthermore, a third experiment showed, for the first time, that PYY (2.5-10.0 microg) can elicit robust feeding when infused directly into the HPC. The significance of these findings to the activation of limbic functions such as memory, reinforcement, and obsessional processes that accompany human binge-eating syndromes is discussed.
Asunto(s)
Acetilcolina/metabolismo , Hipotálamo/metabolismo , Péptido YY/farmacología , Animales , Colina/metabolismo , Antagonistas Colinérgicos/farmacología , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Femenino , Sistema Límbico/fisiología , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Escopolamina/farmacologíaRESUMEN
OBJECTIVE: To test the hypothesis that experience with food restriction produces persistent binge eating. The Minnesota semistarvation experiment and studies of prisoners-of-war show that chronic food restriction produces dramatic changes in eating behavior (including binge eating) that endure decades after restriction has ceased. Bulimia nervosa patients who restrict also binge. Restriction may be a risk factor in the etiology of binge eating and bulimia. METHOD: Animals were subjected to four different patterns of 12-week restriction-refeeding cycles. The rats were either food restricted (dieting) or not restricted and refed regular or palatable food (binging). RESULTS: Thirty days after normalization (full feeding, no restriction cycling), rats with a history of cycles of restriction and hyperphagia continued to exhibit persistent binge eating. This effect was shown particularly with palatable food, in stated conditions, and in response to acute 24-hr deprivation. DISCUSSION: Results from this animal model implicate restriction and overeating on palatable food as biological determinants of binge-eating behaviors, including bulimia nervosa.
Asunto(s)
Bulimia/psicología , Conducta Alimentaria/psicología , Privación de Alimentos , Hiperfagia/psicología , Gusto , Animales , Modelos Animales de Enfermedad , Femenino , Preferencias Alimentarias/psicología , Ratas , Ratas Sprague-DawleyRESUMEN
Opioid antagonism and serotonergic stimulation is associated with macronutrient-specific hypophagia in animals. In the present study we evaluated their systemic effect alone, and in combination, at various doses, on the intake of sweet carbohydrate-rich and sweet fat-rich foods, tastes, and nutrients that are typical of binge-food items. Low-dose (1 mg/kg) naloxone, alone, preferentially suppressed fat-rich intake while low-dose (2.5 mg/kg) fluoxetine, alone, preferentially suppressed carbohydrate-rich intake. Each drug at these doses, combined with various doses of the other (2.5-10 mg/kg fluoxetine; 0.01-1 mg/kg naloxone) additively suppressed both kinds of the sweet foods. Naloxone and fluoxetine have therapeutic potential in treating binge-eating disorders. This animal study suggests what shortcomings and benefits might be expected when combining these two agents.
Asunto(s)
Antidepresivos de Segunda Generación/farmacología , Depresores del Apetito/farmacología , Conducta Alimentaria/efectos de los fármacos , Fluoxetina/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Animales , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Privación de Alimentos/fisiología , Preferencias Alimentarias/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Peptide YY (PYY) administered centrally in rats induces powerful overeating. PYY also occurs endogenously in humans and is elevated in abstaining bulimic patients. To examine the effect of PYY in an environment that parallels some aspects of bulimia, rats were tested in a paradigm associated with approach-avoidance behavior, choosing a preferred (sweet) food paired with shock, over regular food safe from shock. PYY-treated rats chose to sustain shock to retrieve and consume the preferred food, at a significantly greater speed and quantity. The number of approaches that were met without retrieval of food due to anxiety after PYY treatment indicates that PYY increased motivation towards feeding, rather than anxiolysis. This effect of PYY in a model of conflict associated with food choice resembles aspects of bulimic binge-eating, which is characterized by the repetitive, rapid intake of food, despite anxiety associated with this behavior.
Asunto(s)
Apetito/fisiología , Conflicto Psicológico , Ingestión de Alimentos/fisiología , Miedo/fisiología , Preferencias Alimentarias/fisiología , Hormonas Gastrointestinales/fisiología , Péptidos/fisiología , Animales , Nivel de Alerta/fisiología , Aprendizaje por Asociación/fisiología , Femenino , Motivación , Péptido YY , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/fisiología , Respuesta de Saciedad/fisiologíaRESUMEN
Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and MIF-1 (Pro-Leu-Gly-NH2) act as opiate antagonists in various behavioral systems including ingestion. Central injection of peptide YY (PYY) elicits a powerful feeding response in satiated rats, and the opioid antagonist naloxone decreases eating in a variety of conditions including PYY-stimulated eating. Therefore, the aim of this study was to examine the effects of Tyr-MIF-1 and MIF-1 as opiate antagonists on a naloxone-sensitive PYY model of hyperphagia. Naloxone at doses of 1.0 and 10.0 mg/kg, SC, decreased hyperphagia induced by 2.4 micrograms PYY injected in the PVN. MIF-1 and Tyr-MIF-1 had no effect on PYY-induced eating at doses comparable to naloxone (0.1 to 10.0 mg/kg, IP). These results suggest that in this model of eating behavior, Tyr-MIF-1 and MIF-1 do not act as opiate antagonists.
Asunto(s)
Hiperfagia/inducido químicamente , Hormona Inhibidora de la Liberación de MSH/farmacología , Naloxona/farmacología , Péptidos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Hormona Inhibidora de la Liberación de MSH/análogos & derivados , Masculino , Péptido YY , Ratas , Ratas Sprague-DawleyRESUMEN
Central administrations of neuropeptide Y and peptide YY (PYY) produce robust increases in food intake, and this response may be contingent upon the availability of insulin. In contrast, beta 2-adrenergic agonists decrease food intake, and this effect also appears to be dependent on circulating insulin. To investigate a possible interaction between PYY and beta 2-adrenergic function, rats were given systemic injections of terbutaline, a beta 2 agonist, at doses of 0, 5, 10, and 50 mg/kg prior to injections of 0.57 nmol PYY in the paraventricular nucleus of the hypothalamus. Terbutaline pretreatment significantly decreased feeding elicited by PYY in a dose-dependent fashion. This suggests that beta 2-adrenoreceptor activity is involved in PYY-induced feeding.