Area postrema mediates tumor effects on food intake, body weight, and learned aversions

1985 ◽  
Vol 249 (3) ◽  
pp. R296-R300 ◽  
Author(s):  
I. L. Bernstein ◽  
C. M. Treneer ◽  
J. N. Kott
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leydig Cell ◽  
Area Postrema ◽  
Solitary Tract ◽  
Medial Area

Growth of a Leydig cell [LTW (m)] tumor in rats is associated with the development of significant hypophagia and severe aversions to the available diet. Lesions of the area postrema and nearby caudal medial area of the solitary tract were found to block or greatly attenuate the anorexia and food aversions that typically accompany the growth of this tumor. Thus these tumor-induced symptoms may be associated with the detection of blood-borne chemicals by cells located in or near the area postrema.

scholarly journals Increased Hypothalamic Signal Transducer and Activator of Transcription 3 Phosphorylation after Hindbrain Leptin Injection

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1509-1519 ◽  
Author(s):  
Marieke Ruiter ◽  
Patricia Duffy ◽  
Steven Simasko ◽  
Robert C. Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Leptin Receptor ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Solitary Tract ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Transcription 3

Reduction of food intake and body weight by leptin is attributed largely to its action in the hypothalamus. However, the signaling splice variant of the leptin receptor, LRb, also is expressed in the hindbrain, and leptin injections into the fourth cerebral ventricle or dorsal vagal complex are associated with reductions of feeding and body weight comparable to those induced by forebrain leptin administration. Although these observations suggest direct hindbrain action of leptin on feeding and body weight, the possibility that hindbrain leptin administration also activates the Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling in the hypothalamus has not been investigated. Confirming earlier work, we found that leptin produced comparable reductions of feeding and body weight when injected into the lateral ventricle or the fourth ventricle. We also found that lateral and fourth ventricle leptin injections produced comparable increases of STAT3 phosphorylation in both the hindbrain and the hypothalamus. Moreover, injection of 50 ng of leptin directly into the nucleus of the solitary tract also increased STAT3 phosphorylation in the hypothalamic arcuate and ventromedial nuclei. Increased hypothalamic STAT3 phosphorylation was not due to elevation of blood leptin concentrations and the pattern of STAT3 phosphorylation did not overlap distribution of the retrograde tracer, fluorogold, injected via the same cannula. Our observations indicate that even small leptin doses administered to the hindbrain can trigger leptin-related signaling in the forebrain, and raise the possibility that STAT3 phosphorylation in the hypothalamus may contribute to behavioral and metabolic changes observed after hindbrain leptin injections.

Body weight of rats following area postrema ablation: effect of early force-feeding

1989 ◽  
Vol 256 (4) ◽  
pp. R939-R945
Author(s):  
N. J. Kenney ◽  
J. N. Kott ◽  
N. Tomoyasu ◽  
A. J. Bhatia ◽  
A. S. Ruiz ◽  
...  
Keyword(s):  
Body Weight ◽  
Preliminary Analysis ◽  
Area Postrema ◽  
Solitary Tract ◽  
Milk Diet ◽  
Medial Nucleus ◽  
Body Weights ◽  
Force Feeding ◽  
Ad Libitum ◽  
Ad Libitum Feeding

This study examined the effect of intragastric force-feeding of a milk diet on body weights of rats with lesions of the area postrema/caudal medial nucleus of the solitary tract (AP/cmNTS). Force-feeding was conducted over the first 10 days after the ablation. Body weight was monitored both during and after force-feeding. Food intake was measured during all ad libitum feeding periods. During force-feeding, rats with AP/cmNTS lesions gained weight at the same rate as force-fed sham-lesioned rats or sham-lesioned rats that voluntarily ingested an equal amount of the milk. When returned to ad libitum feeding, lesioned rats that had been force-fed were not hypophagic and did not lose weight. Body weights of such rats remained above those of lesioned rats that were not force-fed and similar to those of nonlesioned rats throughout this study. Despite their normal weights, preliminary analysis indicated that body fat of the force-fed lesioned rats may have been reduced. These findings suggest that the effects of AP/cmNTS ablation are multiple and that reduction of body weight need not be the primary effect of such lesions.

scholarly journals GFRAL-expressing neurons suppress food intake via aversive pathways

2021 ◽  
Vol 118 (8) ◽  
pp. e2021357118
Author(s):  
Paul V. Sabatini ◽  
Henriette Frikke-Schmidt ◽  
Joe Arthurs ◽  
Desiree Gordian ◽  
Anita Patel ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Area Postrema ◽  
Mechanisms Of Action ◽  
Parabrachial Nucleus ◽  
Potential Treatment ◽  
Exciting Opportunity ◽  
Wide Range ◽  
Restricted Expression Pattern ◽  
Meal Ingestion

The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α–like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated GfralCre and conditional GfralCreERT mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating GfralCre-expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non–meal-associated pathophysiologic signals to suppress nutrient uptake and absorption.

scholarly journals GABA neurons in the nucleus tractus solitarius express GLP-1 receptors and mediate anorectic effects of liraglutide in rats

2020 ◽  
Vol 12 (533) ◽  
pp. eaay8071 ◽  
Author(s):  
Samantha M. Fortin ◽  
Rachele K. Lipsky ◽  
Rinzin Lhamo ◽  
Jack Chen ◽  
Eun Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Male Rats ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
Cellular Phenotypes ◽  
Sites Of Action

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part through central GLP-1Rs in both the hypothalamus and the hindbrain. Here, we extend findings supporting a role for hindbrain GLP-1Rs in mediating the anorectic effects of liraglutide in male rats. To dissociate the contribution of GLP-1Rs in the area postrema (AP) and the nucleus tractus solitarius (NTS), we examined the effects of liraglutide in both NTS AAV-shRNA–driven Glp1r knockdown and AP-lesioned animals. Knockdown of NTS GLP-1Rs, but not surgical lesioning of the AP, attenuated the anorectic and body weight–reducing effects of acutely delivered liraglutide. In addition, NTS c-Fos responses were maintained in AP-lesioned animals. Moreover, NTS Glp1r knockdown was sufficient to attenuate the intake- and body weight–reducing effects of chronic daily administered liraglutide over 3 weeks. Development of improved obesity pharmacotherapies requires an understanding of the cellular phenotypes targeted by GLP-1R agonists. Fluorescence in situ hybridization identified Glp1r transcripts in NTS GABAergic neurons, which when inhibited using chemogenetics, attenuated the food intake– and body weight–reducing effects of liraglutide. This work demonstrates the contribution of NTS GLP-1Rs to the anorectic potential of liraglutide and highlights a phenotypically distinct (GABAergic) population of neurons within the NTS that express the GLP-1R and are involved in the mediation of liraglutide signaling.

Level of satiety: in vitro energy metabolism in brain during hypophagic and hyperphagic body weight recovery

1989 ◽  
Vol 257 (6) ◽  
pp. R1322-R1327 ◽  
Author(s):  
T. R. Kasser ◽  
R. B. Harris ◽  
R. J. Martin
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Area Postrema ◽  
Tube Feeding ◽  
Acid Oxidation

Rates of in vitro glucose and fatty acid oxidation were examined in four brain sites during hypophagic and hyperphagic recovery of normal body weight. Rats were fed 40, 100, or 160% of normal intake, via gastric intubation, for 3 wk. Another group of rats was starved until body weight loss was equivalent to weight loss in 40%-fed rats. Groups of rats were killed at the conclusion of tube feeding or fasting and at specific periods during recovery of body weight. Brain sites examined were the ventrolateral hypothalamus (VLH), ventromedial hypothalamus (VMH), a caudal brain stem site encompassing the area postrema-nucleus of the solitary tract (AP-NTS), and cortex. During recovery, rats previously fed 160% of normal intake (anorectic) maintained low rates of VLH fatty acid oxidation and were hypophagic until most excess fat was depleted. Conversely, rats previously fed 40% of normal intake (hungry) maintained high rates of VLH fatty acid oxidation and were hyperphagic until most deficient fat was repleted. Rats previously starved maintained high rates of VLH fatty acid oxidation during hyperphagic recovery, although levels of VLH fatty acid oxidation and food intake were initially low on refeeding. Rates of glucose oxidation in the brain sites examined did not relate well to energy balance status and the needed adjustments in food intake. The results indicated that the level of glucose oxidation in the VLH and AP-NTS responded to the level of energy immediately coming into the system (food intake).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals GLP-1 Neurons in the Nucleus of the Solitary Tract Project Directly to the Ventral Tegmental Area and Nucleus Accumbens to Control for Food Intake

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 647-658 ◽  
Author(s):  
Amber L. Alhadeff ◽  
Laura E. Rupprecht ◽  
Matthew R. Hayes
Keyword(s):  
Body Weight ◽  
Nucleus Accumbens ◽  
Food Intake ◽  
Ventral Tegmental Area ◽  
Nucleus Tractus Solitarius ◽  
Receptor Activation ◽  
Current Data ◽  
Solitary Tract ◽  
Ventral Tegmental ◽  
Glucagon Like Peptide 1

Central glucagon-like-peptide-1 (GLP-1) receptor activation reduces food intake; however, brain nuclei and mechanism(s) mediating this effect remain poorly understood. Although central nervous system GLP-1 is produced almost exclusively in the nucleus of the solitary tract in the hindbrain, GLP-1 receptors (GLP-1R) are expressed throughout the brain, including nuclei in the mesolimbic reward system (MRS), e.g. the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Here, we examine the MRS as a potential site of action for GLP-1-mediated control of food intake and body weight. Double immunohistochemistry for Fluorogold (monosynaptic retrograde tracer) and GLP-1 neuron immunoreactivity indicated that GLP-1-producing nucleus tractus solitarius neurons project directly to the VTA, the NAc core, and the NAc shell. Pharmacological data showed that GLP-1R activation in the VTA, NAc core, and NAc shell decreased food intake, especially of highly-palatable foods, and body weight. Moreover, blockade of endogenous GLP-1R signaling in the VTA and NAc core resulted in a significant increase in food intake, establishing a physiological relevance for GLP-1 signaling in the MRS. Current data highlight these nuclei within the MRS as novel sites for GLP-1R-mediated control of food intake and body weight.

scholarly journals Rhythmic neuronal activities of the rat nucleus of the solitary tract are impaired by short-term high fat diet - implications for daily control of satiety by the brainstem

2021 ◽  
Author(s):  
Lukasz Chrobok ◽  
Jasmin D Klich ◽  
Anna M Sanetra ◽  
Jagoda S Jeczmien-Lazur ◽  
Kamil Pradel ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Circadian Rhythms ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Solitary Tract ◽  
High Fat ◽  
Short Term ◽  
Extrinsic Factors

ABSTRACTTemporal partitioning of daily food intake is crucial for survival and involves the integration of internal circadian states and external influences such as the light-dark cycle and the composition of diet. These intrinsic and extrinsic factors are interdependent with misalignment of circadian rhythms promoting body weight gain, while consumption of a calorie dense diet elevates the risk of obesity and blunts circadian rhythms. Since cardiovascular disease, metabolic disorders, and cancer are comorbid with obesity, understanding the relationships between brain activity and diet is of pivotal importance. Recently, we defined for the first time the circadian properties of the dorsal vagal complex of the brainstem, a structure implicated in the control of food intake and autonomic tone, but if and how 24 h rhythms in this area are influenced by diet remains unresolved. Here we focused on a key structure of this complex, the nucleus of the solitary tract, and using a range of approaches, we interrogated how its neuronal and cellular rhythms are affected by high-fat diet. We report that short term consumption of this diet increases food intake during the day and blunts daily rhythms in gene expression and neuronal discharge in the nucleus of the solitary tract. These alterations in this structure occur without prominent body weight gain, suggesting that high-fat diet acts initially to reduce activity in the nucleus of the solitary tract, thereby disinhibiting mechanisms that suppress daytime feeding.GRAPHICAL ABSTRACT

scholarly journals Targeted leptin receptor blockade: role of ventral tegmental area and nucleus of the solitary tract leptin receptors in body weight homeostasis

2014 ◽  
Vol 222 (1) ◽  
pp. 27-41 ◽  
Author(s):  
M Matheny ◽  
K Y E Strehler ◽  
M King ◽  
N Tümer ◽  
P J Scarpace
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Ventral Tegmental Area ◽  
Food Consumption ◽  
Leptin Receptor ◽  
Body Weight Gain ◽  
Solitary Tract ◽  
Leptin Receptors ◽  
Ventral Tegmental

The present investigation examined whether leptin stimulation of ventral tegmental area (VTA) or nucleus of the solitary tract (NTS) has a role in body weight homeostasis independent of the medial basal hypothalamus (MBH). To this end, recombinant adeno-associated viral techniques were employed to target leptin overexpression or overexpression of a dominant negative leptin mutant (leptin antagonist). Leptin antagonist overexpression in MBH or VTA increased food intake and body weight to similar extents over 14 days in rats. Simultaneous overexpression of leptin in VTA with antagonist in MBH resulted in food intake and body weight gain that were less than with control treatment but greater than with leptin alone in VTA. Notably, leptin overexpression in VTA increased P-STAT3 in MBH along with VTA, and leptin antagonist overexpression in the VTA partially attenuated P-STAT3 levels in MBH. Interestingly, leptin antagonist overexpression elevated body weight gain, but leptin overexpression in the NTS failed to modulate either food intake or body weight despite increased P-STAT3. These data suggest that leptin function in the VTA participates in the chronic regulation of food consumption and body weight in response to stimulation or blockade of VTA leptin receptors. Moreover, one component of VTA-leptin action appears to be independent of the MBH, and another component appears to be related to leptin receptor-mediated P-STAT3 activation in the MBH. Finally, leptin receptors in the NTS are necessary for normal energy homeostasis, but mostly they appear to have a permissive role. Direct leptin activation of NTS slightly increases UCP1 levels, but has little effect on food consumption or body weight.

Caudal hindbrain participation in the suppression of feeding by central and peripheral bombesin

1993 ◽  
Vol 264 (6) ◽  
pp. R1229-R1234 ◽  
Author(s):  
E. E. Ladenheim ◽  
R. C. Ritter
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Cerebral Ventricle ◽  
Solitary Tract ◽  
Medial Nucleus ◽  
Neural Substrate

We have previously demonstrated that bombesin (BBS) infused into the fourth cerebral ventricle in rats suppressed feeding at doses 10-1,000 times less than those required after lateral ventricular administration. These results suggest that centrally administered BBS acts in the caudal hindbrain to suppress food intake. To investigate the participation of caudal hindbrain structures in fourth-ventricular BBS-induced suppression of feeding, we made lesions that destroyed the following: 1) area postrema (AP) and 2) and medial nucleus of the solitary tract (NST). Additionally, we examined the role of the AP/NST in the suppression of food intake after peripheral BBS administration. Our experiments revealed that lesions of the AP/NST abolished the suppression of food intake by fourth-ventricular BBS and attenuated the suppression of food intake by peripheral BBS. Lesions restricted to the AP attenuated the suppression of food intake by fourth-ventricular BBS but had no effect on suppression of intake by peripherally administered BBS. These results suggest that the NST may be a common neural substrate for the inhibition of food intake by both centrally and peripherally administered BBS.

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