Inhibitory effect of 5-hydroxytryptamine on hyperphagia in mice with genetic overexpression of neuropeptide Y

Hsiao, Sheng Huang; Chung, Hsien-Hui; Inui, Akio; Tong, Yat Ching; Cheng, Juei Tang

doi:10.1016/j.neulet.2005.10.054

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…The 5-hydroxytryptamine (serotonin) system has long been associated with food intake and body weight regulation. A variety of studies have demonstrated that hypothalamic NPY and POMC are important intermediaries in the serotonin system-induced feeding response (15,16,(41)(42)(43). Serotonin receptor activation inhibits the expression of orexigenic NPY and stimulates the expression of anorexigenic POMC in the hypothalamus (15,16,36).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Ahi1 Mediates Feeding Behavior through Interaction with 5-HT2C Receptor

Wang

Huang

et al. 2012

Journal of Biological Chemistry

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It is indicated that there are important molecules interacting with brain nervous systems to regulate feeding and energy balance by influencing the signaling pathways of these systems, but relatively few of the critical players have been identified. In the present study, we provide the evidence for the role of Abelson helper integration site 1 (Ahi1) protein as a mediator of feeding behavior through interaction with serotonin receptor 2C (5-HT 2C R), known for its critical role in feeding and appetite control. First, we demonstrated the co-localization and interaction between hypothalamic Ahi1 and 5-HT 2C R. Ahi1 promoted the degradation of 5-HT 2C R through the lysosomal pathway. Then, we investigated the effects of fasting on the expression of hypothalamic Ahi1 and 5-HT 2C R. Fasting resulted in an increased Ahi1 expression and a concomitant decreased expression of 5-HT 2C R. Knockdown of hypothalamic Ahi1 led to a concomitant increased expression of 5-HT 2C R and a decrease of food intake and body weight. Last, we found that Ahi1 could regulate the expression of neuropeptide Y and proopiomelanocortin. Taken together, our results indicate that Ahi1 mediates feeding behavior by interacting with 5-HT 2C R to modulate the serotonin signaling pathway.Obesity and its associated ailments such as diabetes have become a worldwide epidemic carrying with them a heavy toll of morbidity and mortality. Over the past decades, it has become evident that neural circuits in the central nervous system play a direct and crucial role in controlling feeding and energy homeostasis (1, 2). Disruptions in the mechanisms of central nervous system energy sensing are able to alter the standard homeostatic responses and are factors that contribute to the pathophysiology of obesity and diabetes. The brain serotonin system has long been implicated in the neural regulation of food intake and energy metabolism, as highlighted by the clinical use of serotonin releasers and reuptake inhibitors as appetite suppressant and weight loss medication (3-5). Depletion of central serotonin using selective neurotoxins has been shown to result in hyperphagia and obesity, whereas the release of serotonin and the inhibition of reuptake by D-fenfluramine potently reduce feeding and body weight (6). More recently, several lines of evidence show that serotonin receptor agonists can significantly improve glucose tolerance and reduce plasma insulin in mouse models of obesity and type 2 diabetes (7-9).Numerous serotonin receptor subtypes have been identified in which serotonin receptor 2C (5-HT 2C R) 4 is recognized specifically as a mediator of serotonin-induced appetite and glucose regulation (10 -13). During the past few years, both pharmacological and genetic evidence has indicated that neuropeptide Y (NPY) and melanocortin systems are the necessary mechanisms by which 5-HT 2C R agonists reduce appetite and improve diabetic conditions (14 -16). Although significant progress has been made in the study of serotonin-mediated regulation of energy metabolism, we ...

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Section: Discussionmentioning

confidence: 99%

Hypothalamic Ahi1 Mediates Feeding Behavior through Interaction with 5-HT2C Receptor

Wang

Huang

et al. 2012

Journal of Biological Chemistry

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“…Brain 5-HT is also known to participate in the maintenance of blood glucose levels [31]. 5-HT administration induces hyperglycemia and reduces hyperphagia in NPY-overexpressing rats via 5-HT 2A receptors [32], and modulates the release of endogenous melanocortin receptor ligands via 5-HT 1B receptors. OH-DPAT, a selective 5-HT 1A agonist, increases blood glucose levels when administered centrally [33].…”

Section: Discussionmentioning

confidence: 99%

Induction of Glucose Intolerance by Acute Administration of Rimonabant

et al. 2012

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Background/Aims: Rimonabant is a cannabinoid CB1 receptor antagonist. Other CB1 antagonists have biphasic effects on blood glucose levels following acute administration. We therefore tested the effects of rimonabant on glucose tolerance following acute administration. Methods: We tested the effects of oral and intracerebroventricular administration of rimonabant on blood glucose and gastrointestinal transit in mice following oral and intravenous glucose challenge. Results: We found a dose-dependent increase in blood glucose from oral doses of rimonabant of 3 mg/kg and above. WIN55,212-2 (3 mg/kg), a cannabinoid receptor agonist, did not influence blood glucose in the presence or absence of rimonabant. Rimonabant did not induce release of glucose from isolated rat hepatocytes or modify serum insulin concentration in mice. Intracerebroventricular administration of rimonabant caused increases in blood glucose and gastrointestinal transit, suggesting a central nervous system site of action. Increases in blood glucose by rimonabant were partially blocked by the dopamine receptor antagonist haloperidol and significantly blocked by the 5-hydroxytryptophan (5-HT) depleting agent p-CPA and the 5-HT₃ receptor antagonist ondansetron. Conclusions: Rimonabant causes a dose-dependent increase in glucose profile upon glucose challenge partially mediated by the central nervous system control of gastrointestinal carbohydrate absorption through pathways that are modulated by both 5-HT and dopamine.

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“…Recientemente Hsiao, Cheng, Inui, Tong y Cheng (2006), reportaron que la administración periférica de 5-HT reduce la hiperfagia de ratones transgénicos con sobre expresión del NPY. La administración de ketanserina fue capaz de revertir el efecto hipofágico inducido por la 5-HT, atribuyendo estos resultados a la participación de receptores 5-HT 2A .…”

Section: Carbohidratosunclassified

Efectos De La 5-Ht en Ratas Pretratadas Con Ketanserina Sobre La Estructura De La Conducta Alimentaria

Díaz¹,

Pérez²,

Alonso³

2011

Analisis de la Conducta

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RESUMENExiste evidencia de que el control serotoninégico sobre la conducta alimentaria es mediado principalmente por receptores 5-HT 1/2 . Sin embargo, no son sufi cientes los datos acerca de los mecanismos conductuales específi cos involucrados. El propósito del presente estudio fue evaluar los efectos de la 5-HT en ratas pretratadas con ketanserina sobre la estructura de la conducta alimentaria con el fi n de revelar la contribución de los receptores 5-HT 2A/2C del núcleo paraventricular hipotalámico (NPH) y el mecanismo conductual específi co involucrado. Cuarenta ratas fueron mantenidas bajo un paradigma de auto-selección dietaria con libre acceso a fuentes separadas de proteínas, carbohidratos, grasas y agua. La estructura de la conducta alimentaria fue registrada durante 20 min. Las ratas se mantuvieron en una habitación a 21 ± 1°C , bajo un ciclo invertido de luz-oscuridad de 12 hrs. Los datos obtenidos indican que el pretratamiento con ketanserina atenuó el efecto supresor de la 5-HT sobre la ingesta de carbohidratos en el arranque del período natu-1. Proyecto financiado por DGAPA, PAPIIT IN304300.

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Inhibitory effect of 5-hydroxytryptamine on hyperphagia in mice with genetic overexpression of neuropeptide Y

Cited by 5 publications

References 12 publications

Hypothalamic Ahi1 Mediates Feeding Behavior through Interaction with 5-HT2C Receptor

Hypothalamic Ahi1 Mediates Feeding Behavior through Interaction with 5-HT2C Receptor

Induction of Glucose Intolerance by Acute Administration of Rimonabant

Efectos De La 5-Ht en Ratas Pretratadas Con Ketanserina Sobre La Estructura De La Conducta Alimentaria

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