Fourth ventricular thyrotropin induces satiety and increases body temperature in rats

Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.

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Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00026.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. R448-R455 ◽

Cited By ~ 25

Author(s):

Jason Wright ◽

Carlos Campos ◽

Thiebaut Herzog ◽

Mihai Covasa ◽

Krzysztof Czaja ◽

...

Keyword(s):

Nmda Receptor ◽

Food Intake ◽

Nmda Receptors ◽

Receptor Antagonist ◽

Fourth Ventricle ◽

Nmda Receptor Antagonist ◽

Behavioral Pattern ◽

Vagal Afferents ◽

Nmda Receptor Antagonists ◽

The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

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Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00785.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. R1565-R1569 ◽

Cited By ~ 17

Author(s):

Kimberly P. Kinzig ◽

Karen A. Scott ◽

Jayson Hyun ◽

Sheng Bi ◽

Timothy H. Moran

Keyword(s):

Gene Expression ◽

Food Intake ◽

Fourth Ventricle ◽

Time Course ◽

Arcuate Nucleus ◽

Central Administration ◽

Stimulatory Action ◽

Hypothalamic Arcuate Nucleus ◽

Ghrelin Receptors ◽

The Brain

The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.

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Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00448.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. R575-R585 ◽

Cited By ~ 82

Author(s):

Éva Szentirmai ◽

Levente Kapás ◽

James M. Krueger

Keyword(s):

Food Intake ◽

Suppressive Effect ◽

Hormone Release ◽

Central Administration ◽

Rapid Eye Movement Sleep ◽

Regulatory Circuit ◽

Intracerebroventricular Injections ◽

The Brain ◽

Brain Peptide

Ghrelin, a gut-brain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 μg (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleep-suppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake- and arousal-promoting network formed by orexin and NPY.

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Fourth ventricle bombesin injection suppresses ingestive behaviors in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.3.r590 ◽

1989 ◽

Vol 256 (3) ◽

pp. R590-R596 ◽

Cited By ~ 2

Author(s):

F. W. Flynn

Keyword(s):

Food Intake ◽

Water Intake ◽

Fourth Ventricle ◽

Home Cage ◽

Saline Injection ◽

Bottle Test ◽

Inhibit Food Intake ◽

Ingestive Behaviors ◽

Intact Rats

Food intake after fourth intracerebroventricular (icv) injections of bombesin (BBS) was measured in intact rats. BBS injections (greater than or equal to 10 ng) reliably suppressed chow intake in 17-h food-deprived rats. Systemic injections of BBS (50 ng) had no effect on food intake. These data indicate that BBS can act directly on caudal brain stem site(s) to inhibit food intake. The behavioral specificity of fourth icv BBS was evaluated by measuring the effects of fourth icv BBS injection on water intake by 17-h water-deprived rats in the presence and absence of food. Fourth icv injections of BBS in doses greater than 10 ng suppressed 30-min and 2-h water intake relative to saline injection when food was available in the home cage. In contrast, when food was not present during the 2-h intake test, fourth icv injections of BBS had no effect on water intake. This suggests that the inhibition of water intake was secondary to the effects of BBS on food intake. Lastly, sucrose (0.1 M) was paired with fourth icv BBS (50 ng), fourth icv saline, and intraperitoneal LiCl (1.5 meq/kg) in three groups of naive rats, and sucrose preference was subsequently measured. Rats that received injections of either saline or BBS preferred sucrose during the 24-h two-bottle test, and their preference ratios were significantly greater than those of the LiCl-injected rats. The role of afferent signals elicited by fourth ventricle BBS administration in the control of food intake is discussed.

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Prolactin-releasing peptide: a new tool for obesity treatment

Journal of Endocrinology ◽

10.1530/joe-16-0046 ◽

2016 ◽

Vol 230 (2) ◽

pp. R51-R58 ◽

Cited By ~ 16

Author(s):

Jaroslav Kuneš ◽

Veronika Pražienková ◽

Andrea Popelová ◽

Barbora Mikulášková ◽

Jana Zemenová ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Binding Affinity ◽

Subcutaneous Administration ◽

Obesity Treatment ◽

Noninvasive Therapy ◽

Food Intake Regulation ◽

Intake Regulation ◽

Prolactin Releasing Peptide ◽

The Brain

Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood–brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP). PrRP is involved in feeding and energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Acute peripheral administration of myristoylated and palmitoylated PrRP analogs to mice and rats induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight, improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity. A strong anorexigenic, body weight-reducing and glucose tolerance-improving effect of palmitoylated-PrRP31 was shown also in diet-induced obese rats after its repeated 2-week-long peripheral administration. Thus, the strong anorexigenic and body weight-reducing effects of palmitoylated PrRP31 and myristoylated PrRP20 make these analogs attractive candidates for antiobesity treatment. Moreover, PrRP receptor might be a new target for obesity therapy.

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Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projections

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00869.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. R247-R258 ◽

Cited By ~ 113

Author(s):

Huiyuan Zheng ◽

Laurel M. Patterson ◽

Curtis B. Phifer ◽

Hans-Rudolf Berthoud

Keyword(s):

Food Intake ◽

Brain Stem ◽

Fourth Ventricle ◽

Nucleus Tractus Solitarius ◽

Meal Size ◽

Gastric Distension ◽

Dorsal Vagal Complex ◽

Melanocortin 4 Receptor ◽

Brown Adipose ◽

The Brain

Metabolic, cognitive, and environmental factors processed in the forebrain modulate food intake by changing the potency of direct controls of meal ingestion in the brain stem. Here, we behaviorally and anatomically test the role of the hypothalamic proopiomelanocortin (POMC) system in mediating some of these descending, indirect controls. Melanotan II (MTII), a stable melanocortin 4 receptor (MC4R) and melanocortin 3 receptor (MC3R) agonist injected into the fourth ventricle near the dorsal vagal complex, potently inhibited 14-h food intake by decreasing meal size but not meal frequency; SHU9119, an antagonist, increased food intake by selectively increasing meal size. Furthermore, MTII injected into the fourth ventricle increased and SHU9119 tended to decrease heart rate and body temperature measured telemetrically in freely moving rats. Numerous α-melanocyte-stimulating hormone-immunoreactive axons were in close anatomical apposition to nucleus tractus solitarius neurons showing c-Fos in response to gastric distension, expressing neurochemical phenotypes implicated in ingestive control, and projecting to brown adipose tissue. In retrograde tracing experiments, a small percentage of arcuate nucleus POMC neurons was found to project to the dorsal vagal complex. Thus melanocortin signaling in the brain stem is sufficient to alter food intake via changing the potency of satiety signals and to alter sympathetic outflow. Although the anatomical findings support the involvement of hypothalamomedullary POMC projections in mediating part of the descending, indirect signal, they do not rule out involvement of POMC neurons in the nucleus tractus solitarius in mediating part of the direct signal.

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Study on Body Mass Index (BMI), Dietary Intake Attitudes, and Nutrient Intake Status according to Sugar-Containing Food Intake Frequency of College Students in Gyeonggi-do

Journal of the Korean Society of Food Science and Nutrition ◽

10.3746/jkfn.2016.45.11.1649 ◽

2016 ◽

Vol 45 (11) ◽

pp. 1649-1657 ◽

Cited By ~ 1

Author(s):

Sun-Choung Ahn ◽

Yoon-Sun Kim

Keyword(s):

College Students ◽

Body Mass Index ◽

Food Intake ◽

Dietary Intake ◽

Body Mass ◽

Nutrient Intake

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Basal Ganglia Herniation into the Fourth Ventricle

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100021119 ◽

1997 ◽

Vol 24 (1) ◽

pp. 62-63 ◽

Cited By ~ 1

Author(s):

Mensura Altumbabic ◽

Marc R. Del Bigio ◽

Scott Sutherland

Keyword(s):

Basal Ganglia ◽

Intracerebral Hemorrhage ◽

Fourth Ventricle ◽

Transtentorial Herniation ◽

Intracerebral Bleeding ◽

Rare Phenomenon ◽

The Brain

ABSTRACT:Background:Transtentorial herniation of large cerebral fragments is a rare phenomenon.Method:Case StudyResults:Examination of the brain of a 35-year-old male showed massive intracerebral hemorrhage resulting in displacement of basal ganglia components into the fourth ventricle.Conclusions:Sufficiently rapid intracerebral bleeding can dissect fragments of cerebrum and displace them long distances across the tentorial opening.

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