Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids

Appleyard, Suzanne M.; Bailey, Timothy W.; Doyle, Mark; Jin, Young Ho; Smart, James L.; Low, Malcolm J.; Andresen, Michael

doi:10.1523/jneurosci.4177-04.2005

Cited by 167 publications

(181 citation statements)

References 45 publications

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“…We, therefore, hypothesize that before this signal, mediated by vagal afferents, reaches the ARC, integration occurs with other signals related to food intake and energy balance (such as sugar intake). There is evidence that POMC neurons of the nucleus of the solitary tract (NTS) are activated by incoming afferents from liver and gastrointestinal tract; 28 however, whether the NTS is the location where integration takes place remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

et al. 2009

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Objectives:The mechanisms for how saturated fat and sugar-based beverages contribute to human obesity are poorly understood. This paper describes a series of experiments developed to examine the response of hypothalamic neuropeptides to diets rich in sugar and fat, using three different diets: a high-fat high-sugar (HFHS) choice diet with access to chow, saturated fat and a 30% sugar solution; a high-fat (HF) choice diet with access to chow and saturated fat; or to a high-sugar (HS) choice diet with access to chow and a sugar solution. Method: We first studied caloric intake, body weight gain, hormonal alterations and hypothalamic neuropeptide expression when male Wistar rats were subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. Next, we studied caloric intake and body weight gain when rats were subjected to the choice diets for 5 weeks. Finally, we measured neuropeptide expression in hepatic vagotomized rats subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. Results: In rats on an HF choice diet, plasma leptin concentrations and proopiomelanocortin (POMC) mRNA increased and neuropeptide Y (NPY) mRNA decreased. Rats on an HFHS choice diet showed identical plasma leptin concentrations as rats on an HF choice diet. However, NPY mRNA increased and POMC mRNA decreased. An HS choice diet for 1 week did not alter hypothalamic neuropeptide expression or plasma leptin concentrations. As hormonal changes did not explain the differences in hypothalamic neuropeptide expression between rats on the choice diets, we addressed whether neuronal feedback signals mediated the hypothalamic neuropeptide response. The POMC mRNA response to different diets depended on an intact innervation of liver and upper intestinal tract. Conclusion: Our data suggest that the specific combination of saturated fat and a 30% sugar solution results in hyperphagiainduced obesity and alters hypothalamic neuropeptide expression, and that the response of the melanocortin system is mediated by the hepatic vagus.

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Section: Discussionmentioning

confidence: 99%

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

et al. 2009

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“…These findings were supported by increased levels of Pomc expression in their brainstem, as POMC neurons in the nucleus tractus solitarius have been shown to relay satiety signals from the periphery to the hypothalamus. 46 In parallel, in the liver, leptin and insulin lead to AMPK activation and ghrelin to AMPK suppression. 39 Activation of AMPK in the liver leads to inhibition of fatty acid synthesis and increased fatty acid oxidation.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous caloric restriction associated with increased leptin levels in obesity-resistant αMUPA mice

et al. 2010

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Background: aMUPA mice carry as a transgene the cDNA encoding urokinase-type plasminogen activator, a member of the plasminogen/plasmin system that functions in fibrinolysis and extracellular proteolysis. These mice spontaneously consume less food when fed ad libitum and live longer compared with wild-type (WT) control mice. aMUPA mice are obesity resistant and they share many similarities with calorically restricted animals. However, extensive metabolic characterization of this unique transgenic model has never been performed. Method: Metabolism of aMUPA mice was analyzed by measuring hormone, lipid and glucose levels in the serum, as well as gene and protein expression levels in the liver, hypothalamus and brainstem. Results: aMUPA mice were found to be leaner than WT mice mainly because of reduced fat depots. Serum analyses showed that aMUPA mice have high levels of the anorexigenic hormones insulin and leptin, and low levels of the orexigenic hormone ghrelin. Analyses of brain neuropeptides showed that the transcript of the anorexigenic neuropeptide Pomc is highly expressed in the brainstem, whereas the expression of the orexigenic neuropeptides Npy, Orexin and Mch is blunted in the hypothalamus of aMUPA mice. In addition, adenosine monophosphate (AMP)-activated protein kinase (AMPK) levels were higher in the liver and lower in the hypothalamus, thus promoting simultaneously central reduction in appetite and peripheral loss of fat. The levels of SIRT1 were low in the liver, but high in the hypothalamus, a feature that aMUPA mice share with calorically restricted animals. Conclusion: Taken together, aMUPA mice exhibit a unique metabolic phenotype of low-calorie intake and high leptin levels, and could serve as a model for both spontaneous calorie restriction and resistance to obesity.

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“…This is surprising because 2CR are expressed in both the Arc and PVN (27,28), because pharmacological data implicate both the PVN and Arc in the serotonergic control of eating (50,59), because 2CR-serotonergic inputs to the Arc-PVN melanocortinergic neurons appear to be part of the physiological control of eating in mice (3,36,38), and because both the PVN and the Arc have been implicated in the satiating action of CCK (13,17,35,37,38,42). Furthermore, the absence of CCK-induced c-Fos activation in the NTS of 2CR KO mice suggests that NTS-tohypothalamus signaling would be reduced.…”

Section: Discussionmentioning

confidence: 99%

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

Asarian

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Asarian L. Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors. Am J Physiol Regul Integr Comp Physiol 296: R51-R56, 2009. First published November 12, 2008 doi:10.1152/ajpregu.90655.2008.-To investigate the role of serotonin 2C receptors (2CR), which are expressed only in the central nervous system, in the satiating actions of the gut peptides CCK and glucagon-like peptide 1 (GLP-1), we examined 1) the effect of null mutations of serotonin 2CR (2CR KO) on the eating-inhibitory potencies of dark-onset intraperitoneal injections of 0.9, 1.7, or 3.5 nmol/kg (1, 2, or 4 g/kg) CCK and 100, 200, and 400 nmol/kg (33, 66, or 132 g/kg) GLP-1, and 2) the effects of intraperitoneal injections of 1.7 nmol//kg CCK and 100 nmol/kg GLP-1 on neuronal activation in the brain, as measured by c-Fos expression. All CCK and GLP-1 doses decreased 30-min food intake in wild-type (WT) mice, but none of them did in 2CR KO mice. CCK increased the number of cells expressing c-Fos in the nucleus tractus solitarii (NTS) of WT, but not 2CR KO mice. CCK induced similar degrees of c-Fos expression in the paraventricular (PVN) and arcuate (Arc) nuclei of the hypothalamus of both genotypes. GLP-1, on the other hand, increased c-Fos expression similarly in the NTS of both genotypes and increased c-Fos expression more in the PVN and Arc of 2CR KO mice, but not WT mice. These results indicate that serotonin signaling via serotonin 2CR is necessary for the full satiating effects of CCK and GLP-1. In addition, they suggest that the satiating effects of the two peptides are mediated by different neural mechanisms. endocrine; eating; hormone; neural; immunocytochemistry; 5HT ON THE BASIS OF FULFILLMENT of criteria for endocrine satiation signals initially proposed by Gibbs et al. (20), intestinal CCK and GLP-1 are now considered to be physiological controls of eating (4,10,19,32). Both hormones are released during meals, and premeal administration of doses producing plasma hormone levels that are similar to prandial levels is sufficient to inhibit meal size in the absence of adverse effects in humans. Furthermore, administration of CCK 1 receptor antagonists in humans or rats, or GLP-1 receptor antagonists in rats, increases food intake (Williams D, personal communication); CCK 1 receptor antagonists also block the satiating effects of CCK secretagogues in humans and rats. Although the understanding of the roles of these peptides in physiology of eating has increased tremendously in the last two decades (19,39,41,54), the brain mechanisms underlying their effects are still unclear.Serotonin appears to be a key neurotransmitter in the central mediation of eating, including the control of meal size. Extracellular concentrations of serotonin and its metabolite 5-HIAA increase in rats' brains during spontaneous meals (44). The serotonin agonist fenfluramine, which both releases synaptic serotonin and blocks serotonin reuptake (14, 21), inhibits eating in rats by reducing meal size without affectin...

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Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids

Abstract: The nucleus tractus solitarius (NTS) receives dense terminations from cranial visceral afferents

Cited by 167 publications

References 45 publications

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

Spontaneous caloric restriction associated with increased leptin levels in obesity-resistant αMUPA mice

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

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