Hypothalamic serotonin in the control of meal patterns and macronutrient selection

Shor‐Posner, Gail; Grinker, Joel A.; Marinescu, Constantine; Brown, Owen; Leibowitz, Sarah F.

doi:10.1016/0361-9230(86)90198-x

Cited by 184 publications

(51 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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...

show abstract

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

View full text Add to dashboard Cite

show abstract

“…M-CPP also reduced the grams of protein ingested in the bulimics, but not the grams of protein ingested in the controls. The case for a role of 5-HT in the direct regulation of protein intake is controversial and weak, and most of his work has been done in animals (Anderson 1979;Curtis-Prior 1983;Shor-Posner et al 1986;Fernstrom 1987;Peters and Harper 1987), so these data are provocative.…”

Section: Discussionmentioning

confidence: 99%

Testmeal Responses Following m-Chlorophenylpiperazine and L-Tryptophan in Bulimics and Controls

Brewerton

Murphy

Jimerson

1994

Neuropsychopharmacol

View full text Add to dashboard Cite

A wealth of data support a role for serotonin (5-HT) function in the mediation of satiety responses, that are impaired in patients with bulimia nervosa. Testmeal results are presented in which 26 bulimic patients and 17 normal controls were given in randomized, double-blind-fashion, placebo, and the 5-HT agents m-chlorophenylpiperazine (m-CPP, 0.5 mglkg p.o.) and L-tryptophan (L-TRP, 100 mglkg I. V.). Three and one-half hours after drug administration, subjects were allowed to eat and lib from a standardized testmeal of 3,500 calories, after which postprandial vomiting was not allowed. M-CPP, but not L-TRP, significantly decreased meal size in the combined group, the controls, and to a lesser extent, the bulimics (p � .06). Maximum m-CPP Serotonergic manipulations are known to result in marked changes in feeding behaviors, particularly sati ety responses (Blundell 1977(Blundell , 1984(Blundell , 1986Blundell and Latham, 1978, 1982Latham and Blundell 1979;Samanin et al. 1982;Silverstone and Goodall 1986;Garattini et al., 1988Garattini et al., , 1989, which are dysfunctional in bulimic patients (Owen et al. 1985;Chiodo and Latimer 1986;Kissileff et al. 1986). Pharmacologic en hancement of 5-HT neurotransmission in animals and concentrations were inversely correlated to the number of calories consumed in the total group. Following m-CPP, there were significant decreases in carbohydrate, protein, and fat intake in the total group of subjects. There were also trends for decreased carbohydrate and protein intake in the bulimics following m-CPP. There were trends for both m-CPP and L-TRP to reduce fat intake in the controls. Differences in the effects between m-CPP and L-TRP are likely due to differential involvement of 5-HT receptor subtypes at presynaptic and postsynaptic sites. These studies in humans confirm reports in animals that m-CPP decreases food intake, including carbohydrates, protein, and fat in a mixed testmeal.

show abstract

“…The two lower doses mimicked concentrations of NFFL that may reach the brain after oral administration of doses of NFFL that influence food intake and peripheral metabolism. The highest (5 ~g) dose was comparable to the doses used in previous studies in which feeding behavior was studied (21,22,42). In Experiment 2, 0.3 mg/kg of the 5-HT~ antagonist, (S)-(-)propranolol (Sigma, St. Louis, MO) ( 13,16), dissolved in 0.5 ml saline, was intravenously injected prior to and during intrahypothalamical infusion of the highest dose of NFFL.…”

Section: Infusion Solutionsmentioning

confidence: 99%

“…It also directly activates postsynaptic serotonergic receptors when administered in high concentrations (27). The anorectic effects of NFFL, i.e., inhibition of total food intake and changes in food preference, are mediated by 5-HT receptors in the brain, in particular postsynaptic 5-HTt receptors in the paraventricular nucleus of the hypothalamus (PVN) (21)(22)(23)42). Furthermore, effects of NFFL on peripheral energy metabolism also contribute to the anorectic action of NFFL (10,29,30).…”

mentioning

confidence: 99%

Metabolic and hormonal responses to hypothalamic administration of norfenfluramine in rats

Scheurink

Leuvenink

Steffens

1993

Physiology & Behavior

View full text Add to dashboard Cite

Hypothalamic serotonin in the control of meal patterns and macronutrient selection

Cited by 184 publications

References 42 publications

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

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

Testmeal Responses Following m-Chlorophenylpiperazine and L-Tryptophan in Bulimics and Controls

Metabolic and hormonal responses to hypothalamic administration of norfenfluramine in rats

Contact Info

Product

Resources

About