scholarly journals Integrated Effects of Leptin in the Forebrain and Hindbrain of Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2663-2675 ◽  
Author(s):  
Bhavna N. Desai ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Body Fat ◽  
Fourth Ventricle ◽  
Third Ventricle ◽  
Male Rats ◽  
Low Doses ◽  
Sprague Dawley ◽  
The Third ◽  
Stat3 Phosphorylation

Abstract Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. It is unclear how leptin activity in these areas is integrated. We tested whether both forebrain and hindbrain ObRs have to be activated simultaneously to change energy balance and to maintain metabolic homeostasis. Previous studies used acute leptin injections in either the third ventricle (1–5 μg) or the fourth ventricle (3–10 μg); here we used 12-day infusions of low doses of leptin in one or both ventricles (0.1 μg/24 h in third, 0.6 μg/24 h in fourth). Male Sprague Dawley rats were fitted with third and fourth ventricle cannulas, and saline or leptin was infused from Alzet pumps for 6 or 12 days. Rats that received leptin into only the third or the fourth ventricle were not different from controls that received saline in both ventricles. By contrast, rats with low-dose leptin infusions into both the third and fourth ventricle showed a dramatic 60% reduction in food intake that was reversed on day 6, a 20% weight loss that stabilized on day 6, and a 50% decrease in body fat at day 12 despite the correction of food intake. They displayed normal activity and maintained energy expenditure despite weight loss, indicating inappropriately high thermogenesis that coincided with increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in the brainstem. Altogether, these findings show that with low doses of leptin, chronic activation of both hypothalamic and brainstem ObRs is required to reduce body fat.

scholarly journals Blockade of the cerebral aqueduct in rats provides evidence of antagonistic leptin responses in the forebrain and hindbrain

2014 ◽  
Vol 306 (4) ◽  
pp. E414-E423 ◽  
Author(s):  
Michael I. Vaill ◽  
Bhavna N. Desai ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Body Fat ◽  
Fourth Ventricle ◽  
Third Ventricle ◽  
Cerebral Aqueduct ◽  
Sprague Dawley ◽  
Leptin Receptors ◽  
The Third ◽  
Inhibit Food Intake

Previously, we reported that low-dose leptin infusions into the fourth ventricle produced a small but significant increase in body fat. These data contrast with reports that injections of higher doses of leptin into the fourth ventricle inhibit food intake and weight gain. In this study, we tested whether exogenous leptin in the fourth ventricle opposed or contributed to weight loss caused by third ventricle leptin infusion by blocking diffusion of CSF from the third to the fourth ventricle. Male Sprague-Dawley rats received third ventricle infusions of PBS or 0.3 μg leptin/24 h from miniosmotic pumps. After 4 days, rats received a 3-μl cerebral aqueduct injection of saline or of thermogelling nanoparticles (hydrogel) that solidified at body temperature. Third ventricle leptin infusion inhibited food intake and caused weight loss. Blocking the aqueduct exaggerated the effect of leptin on food intake and weight loss but had no effect on the weight of PBS-infused rats. Leptin reduced both body fat and lean body mass but did not change energy expenditure. Blocking the aqueduct decreased expenditure of rats infused with PBS or leptin. Infusion of leptin into the third ventricle increased phosphorylated STAT3 in the VMHDM of the hypothalamus and the medial NTS in the hindbrain. Blocking the aqueduct did not change hypothalamic p-STAT3 but decreased p-STAT3 in the medial NTS. These results support previous observations that low-level activation of hindbrain leptin receptors has the potential to blunt the catabolic effects of leptin in the third ventricle.

scholarly journals Low-dose leptin infusion in the fourth ventricle of rats enhances the response to third-ventricle leptin injection

2017 ◽  
Vol 313 (2) ◽  
pp. E134-E147 ◽  
Author(s):  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Low Dose ◽  
Respiratory Exchange Ratio ◽  
Third Ventricle ◽  
Separate Experiment ◽  
Rapid Weight Loss ◽  
Leptin Receptors ◽  
The Third

We previously reported that low-dose leptin infusions into the third or fourth ventricle that do not affect energy balance when given independently cause rapid weight loss when given simultaneously. Therefore, we tested whether hindbrain leptin enhances the response to forebrain leptin or whether forebrain leptin enhances the response to hindbrain leptin. Rats received fourth-ventricle infusions of saline or 0.01, 0.1, 0.3, or 0.6 μg leptin/day for 13 days. On days 9 and 13, 0.1 μg leptin was injected into the third ventricle. The injection inhibited food intake for 36 h in saline-infused rats but for 60 h in those infused with 0.6 μg leptin/day. Leptin injection increased intrascapular brown fat temperature in leptin-infused, but not saline-infused, rats. In a separate experiment, rats received third-ventricle infusions of saline or 0.005, 0.01, 0.05, or 0.1 μg leptin/day and fourth-ventricle injections of 1.0 μg leptin on days 9 and 13. Leptin injection inhibited food intake, respiratory exchange ratio, and 14-h food intake in rats infused with saline or the two lowest doses of leptin. There was no effect with higher-dose leptin infusions because food intake, body fat, and lean mass were already inhibited. These data suggest that activation of leptin receptors in the hindbrain enhances the response to third-ventricle leptin, whereas activation of forebrain leptin receptors does not enhance the response to fourth-ventricle leptin, consistent with our previous finding that weight loss in rats treated with fourth-ventricle leptin is associated with indirect activation of hypothalamic STAT3.

scholarly journals Leptin in the hindbrain facilitates phosphorylation of STAT3 in the hypothalamus

2015 ◽  
Vol 308 (5) ◽  
pp. E351-E361 ◽  
Author(s):  
Bhavna N. Desai ◽  
Ruth B. S. Harris
Keyword(s):  
Fourth Ventricle ◽  
Low Dose ◽  
Arcuate Nucleus ◽  
Third Ventricle ◽  
Ventromedial Hypothalamus ◽  
Sprague Dawley ◽  
Brain Nuclei ◽  
Dorsomedial Hypothalamus ◽  
The Third ◽  
Integrated Response

Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. We recently used low-dose leptin infusions to show that chronic activation of both hypothalamic and hindbrain ObRs is required to reduce body fat. The objective of the present study was to identify the brain nuclei that are selectively activated in rats that received chronic infusion of leptin in both the forebrain and hindbrain. Either saline or leptin was infused into third and fourth ventricles (0.1 μg/24 h in the third ventricle and 0.6 μg/24 h in the fourth ventricle) of male Sprague-Dawley rats for 6 days using Alzet pumps. Rats infused with leptin into both ventricles (LL rats) showed a significant increase in phosphorylated (p)STAT3 immunoreactivity in the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and posterior hypothalamus compared with other groups. No differences in pSTAT3 immunoreactivity were observed in midbrain or hindbrain nuclei despite a sixfold higher infusion of leptin into the fourth ventricle than the third ventricle. ΔFosB immunoreactivity, a marker of chronic neuronal activation, showed that multiple brain nuclei were chronically activated due to the process of infusion, but only the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and ventral tuberomamillary nucleus showed a significant increase in LL rats compared with other groups. These data demonstrate that low-dose leptin in the hindbrain increases pSTAT3 in areas of the hypothalamus known to respond to leptin, supporting the hypothesis that leptin-induced weight loss requires an integrated response from both the hindbrain and forebrain.

Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity

1988 ◽  
Vol 255 (6) ◽  
pp. R974-R981 ◽  
Author(s):  
K. Arase ◽  
J. S. Fisler ◽  
N. S. Shargill ◽  
D. A. York ◽  
G. A. Bray
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Third Ventricle ◽  
Sprague Dawley ◽  
High Fat ◽  
Low Fat ◽  
The Third ◽  
Intracerebroventricular Infusion

We examined the effect of dietary fat on the response to 3-hydroxybutyrate (3-OHB) and insulin infused chronically into the third ventricle in three strains of rats with differing susceptibility to obesity induced by a high-fat diet: Osborne-Mendel rats are most susceptible; Sprague-Dawley-rats are intermediate; and S 5B/Pl rats are most resistant. Ten days after implantation of cannulas into the third ventricle, rats were fed either a low-fat diet or a high-fat diet for 14 days. On day 7, osmotic minipumps were attached to the ventricular cannulas. 3-OHB infusions (3.6 mumol/24 h) reduced food intake and body weight in Sprague-Dawley and Osborne-Mendel rats eating either diet. The dietary fat-resistant S 5B/Pl rats did not respond to the intracerebroventricular infusion of 3-OHB. The infusion of insulin (10 mU/24 h) lowered food intake and body weight in animals eating the low-fat (high-carbohydrate) diet but not in animals eating the high-fat diet. Diet profoundly affects the response to intracerebroventricular infusions of insulin but is without effect on the response to 3-OHB.

scholarly journals Acute injection of ASP in the third ventricle inhibits food intake and locomotor activity in rats

2011 ◽  
Vol 301 (1) ◽  
pp. E232-E241 ◽  
Author(s):  
Christian Roy ◽  
Marie-Claude Roy ◽  
Danny Gauvreau ◽  
Anne-Marie Poulin ◽  
Fun-Qun Tom ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Third Ventricle ◽  
Total Activity ◽  
Male Rats ◽  
The Third ◽  
Daily Body Weight ◽  
Acute Injection ◽  
Deficient Mice

Acylation-stimulating protein (ASP; also known as C3adesArg) stimulates triglyceride synthesis and glucose transport via interaction with its receptor C5L2, which is expressed peripherally (adipose tissue, muscle) and centrally. Previous studies have shown that ASP-deficient mice (C3KO) and C5L2-deficient mice (C5L2KO) are hyperphagic (59 to 229% increase, P < 0.0001), which is counterbalanced by increased energy expenditure measured as oxygen consumption (V̇o2) and a lower RQ. The aim of the present study was to evaluate ASP's effect on food intake, energy expenditure, and neuropeptide expression. Male rats were surgically implanted with intracerebroventricular (icv) cannulas directed toward the third ventricle. After a 5-h fast, rats were injected, and food intake was assessed at 0.5, 1, 2, 4, 16, 24, and 48 h, with a 5- to 7-day washout period between each injection. Acute icv injections of ASP (0.3–1,065 pmol) had a time-dependent effect on decreasing food intake by 20 to 57% ( P < 0.05). Decreases were detected by 30 min (maximum 57%, P < 0.01) and at the highest dose effects extended to 48 h (19%, P < 0.05, 24- to 48-h period). Daily body weight gain was decreased by 131% over the first 24 h and 29% over the second 24 h ( P < 0.05). A conditioned taste aversion test indicated that there was no malaise. Furthermore, acute ASP injection affected energy substrate usage, demonstrated by decreased V̇o2 and RQ ( P < 0.05; implicating greater fatty acid usage), with a 49% decrease in total activity over 24 h ( P < 0.05). ASP administration also increased anorexic neuropeptide POMC expression (44%) in the arcuate nucleus, with no change in NPY. Altogether ASP may have central in addition to peripheral effects.

Protein appetite is increased after central leptin-induced fat depletion

2007 ◽  
Vol 293 (4) ◽  
pp. R1468-R1473 ◽  
Author(s):  
Michael F. Wiater ◽  
Bryan D. Hudson ◽  
Yvette Virgin ◽  
Sue Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Fat ◽  
Caloric Intake ◽  
Sprague Dawley ◽  
Body Protein ◽  
Macronutrient Selection ◽  
Daily Diet ◽  
Nadir Point ◽  
And Control

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a “fatless” animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test. Despite these dramatic differences in macronutrient selection, total daily caloric intake did not differ between groups except on day 2. Thus controls of food intake related to ongoing metabolic and nutritional requirements may supersede the negative feedback signals related to body fat stores.

Neuroendoscopic Aspiration of Blood Clots in the Cerebral Aqueduct and Third Ventricle During Posterior Fossa Surgery in the Prone Position

2018 ◽  
Vol 17 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Alberto Feletti ◽  
Riccardo Stanzani ◽  
Matteo Alicandri-Ciufelli ◽  
Giuliano Giliberto ◽  
Matteo Martinoni ◽  
...  
Keyword(s):  
Prone Position ◽  
Posterior Fossa ◽  
Fourth Ventricle ◽  
Blood Clot ◽  
Third Ventricle ◽  
Cerebral Aqueduct ◽  
Posterior Fossa Surgery ◽  
The Third ◽  
Blood Clots ◽  
Surgical Field

AbstractBACKGROUNDDuring surgery in the posterior fossa in the prone position, blood can sometimes fill the surgical field, due both to the less efficient venous drainage compared to the sitting position and the horizontally positioned surgical field itself. In some cases, blood clots can wedge into the cerebral aqueduct and the third ventricle, and potentially cause acute hydrocephalus during the postoperative course.OBJECTIVETo illustrate a technique that can be used in these cases: the use of a flexible scope introduced through the opened roof of the fourth ventricle with a freehand technique allows the navigation of the fourth ventricle, the cerebral aqueduct, and the third ventricle in order to explore the cerebrospinal fluid pathways and eventually aspirate blood clots and surgical debris.METHODSWe report on one patient affected by an ependymoma of the fourth ventricle, for whom we used a flexible neuroendoscope to explore and clear blood clots from the cerebral aqueduct and the third ventricle after the resection of the tumor in the prone position. Blood is aspirated with a syringe using the working channel of the scope as a sucker.RESULTSA large blood clot that was lying on the roof of the third ventricle was aspirated, setting the ventricle completely free. Other clots were aspirated from the right foramen of Monro and from the optic recess.CONCLUSIONWe describe this novel technique, which represents a safe and efficient way to clear the surgical field at the end of posterior fossa surgery in the prone position. The unusual endoscopic visual perspective and instrument maneuvers are easily handled with proper neuroendoscopic training.

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.

Critical surgical anatomy of the ventricular system

2010 ◽  
pp. 674-680
Author(s):  
George Samandouras
Keyword(s):  
Fourth Ventricle ◽  
Third Ventricle ◽  
Surgical Anatomy ◽  
Ventricular System ◽  
The Third ◽  
Lateral Ventricles ◽  
System P

Chapter 12.1 covers critical surgical anatomy of the ventricular system, including brief surgical embryology, brief clinical histology, the lateral ventricles, the third ventricle, the fourth ventricle, and major cisterns.

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