Prevention of reflex natriuresis after acute unilateral nephrectomy by neonatal administration of MSG

1987 ◽  
Vol 252 (2) ◽  
pp. F276-F282 ◽  
Author(s):  
S. Y. Lin ◽  
E. Wiedemann ◽  
C. F. Deschepper ◽  
R. H. Alper ◽  
M. H. Humphreys
Keyword(s):  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Brain Regions ◽  
Anterior Lobe ◽  
Unilateral Nephrectomy ◽  
Reflex Pathways ◽  
Before And After ◽  
Hypothalamic Arcuate Nucleus ◽  
The Central Nervous System ◽  
Neonatal Administration

Acute unilateral nephrectomy (AUN) results in natriuresis from the remaining kidney through reflex pathways involving the central nervous system and requiring an intact pituitary gland. The natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the N-terminal fragment (NTF) of proopiomelanocortin. We measured plasma immunoreactive NTF-like material (IR-NTF) before and after AUN in control rats and rats treated neonatally with monosodium glutamate (MSG), a procedure that produces neuroendocrine dysfunction by destroying cell bodies in the hypothalamic arcuate nucleus, median eminence, and other brain regions. In control rats, IR-NTF increased from 85.8 +/- 54.9 (SD) to 207 +/- 98.1 fmol/ml after AUN (P less than 0.02) as sodium excretion (UNaV) doubled. In MSG-treated rats, AUN produced no change in plasma IR-NTF concentration (58.8 +/- 21.3 vs. 68.3 +/- 18.5 fmol/ml (P = NS), nor did UNaV increase. Tissue content of IR-NTF was reduced in the arcuate nucleus and anterior lobe of pituitaries from MSG-treated rats compared with controls, but was no different in the neurointermediate lobe. These results indicate that the hypothalamic lesion produced by neonatal administration of MSG prevents both the increase in plasma IR-NTF concentration and the natriuresis after AUN, and therefore lend further support to the concept of a causal relationship between these two consequences of AUN.

scholarly journals Hypothyroidism Compromises Hypothalamic Leptin Signaling in Mice

2013 ◽  
Vol 27 (4) ◽  
pp. 586-597 ◽  
Author(s):  
Claudia Groba ◽  
Steffen Mayerl ◽  
Alies A. van Mullem ◽  
Theo J. Visser ◽  
Veerle M. Darras ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Double Knockout ◽  
Hypothalamic Arcuate Nucleus ◽  
The Central Nervous System ◽  
Leptin Expression ◽  
The Impact

Abstract The impact of thyroid hormone (TH) on metabolism and energy expenditure is well established, but the role of TH in regulating nutritional sensing, particularly in the central nervous system, is only poorly defined. Here, we studied the consequences of hypothyroidism on leptin production as well as leptin sensing in congenital hypothyroid TRH receptor 1 knockout (Trhr1 ko) mice and euthyroid control animals. Hypothyroid mice exhibited decreased circulating leptin levels due to a decrease in fat mass and reduced leptin expression in white adipose tissue. In neurons of the hypothalamic arcuate nucleus, hypothyroid mice showed increased leptin receptor Ob-R expression and decreased suppressor of cytokine signaling 3 transcript levels. In order to monitor putative changes in central leptin sensing, we generated hypothyroid and leptin-deficient animals by crossing hypothyroid Trhr1 ko mice with the leptin-deficient ob/ob mice. Hypothyroid Trhr1/ob double knockout mice showed a blunted response to leptin treatment with respect to body weight and food intake and exhibited a decreased activation of phospho-signal transducer and activator of transcription 3 as well as a up-regulation of suppressor of cytokine signaling 3 upon leptin treatment, particularly in the arcuate nucleus. These data indicate alterations in the intracellular processing of the leptin signal under hypothyroid conditions and thereby unravel a novel mode of action by which TH affects energy metabolism.

Partial saturation and regional variation in the blood-to-brain transport of leptin in normal weight mice

2000 ◽  
Vol 278 (6) ◽  
pp. E1158-E1165 ◽  
Author(s):  
William A. Banks ◽  
Cecilia M. Clever ◽  
Catherine L. Farrell
Keyword(s):  
Arcuate Nucleus ◽  
Maximum Velocity ◽  
Brain Perfusion ◽  
Serum Levels ◽  
Brain Regions ◽  
Normal Weight ◽  
Normal Serum ◽  
Optimal Function ◽  
The Central Nervous System ◽  
The Brain

Impaired blood-brain barrier transport of leptin into the arcuate nucleus has been suggested to underlie obesity in humans and outbred aging mice. Here, we used a brain perfusion method in mice to measure transport rates and kinetic parameters for leptin at vascular concentrations between 0.15 and 130 ng/ml. Transport into whole brain was partially saturated at all concentrations, not only those seen in obesity. Leptin entered all regions of the brain, not only the hypothalamus, with entry and saturation rates differing among the brain regions. The value of the Michaelis-Menten constant of the transporter approximates normal serum levels and the maximum velocity value varies significantly among brain regions. These results suggest an important role for low serum levels signaling starvation status to the brain and show that the levels of leptin seen in obesity greatly saturate the transporter. Differences in regional uptake and saturation provide a mechanism by which leptin can control events mediated at the arcuate nucleus and other regions of the central nervous system with different regional thresholds for optimal function.

Mechanism of the induction of brain c-Fos-positive neurons by lipid absorption

2007 ◽  
Vol 292 (1) ◽  
pp. R268-R273 ◽  
Author(s):  
Chun-Min Lo ◽  
Liyun Ma ◽  
Dian Ming Zhang ◽  
Rachel Lee ◽  
Abby Qin ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Lipid Absorption ◽  
Neuronal Activation ◽  
Positive Neuron ◽  
The Central Nervous System ◽  
Chylomicron Formation ◽  
The Brain

Many gastrointestinal meal-related signals are transmitted to the central nervous system via the vagus nerve and thereby control changes in meal size. The c-Fos-positive neuron has been used as a marker of neuronal activation after lipid meals to examine the contribution of a selective macronutrient on brain neurocircuit activity. In rats fed Intralipid, the c-Fos-positive neurons were highly stimulated in the nucleus of the solitary tract (NTS) and in the hypothalamus, including the paraventricular nucleus (PVN), arcuate nucleus of the hypothalamus (ARC), and ventromedial hypothalamus at 4 h lipid feeding. However, c-Fos-like immunoreactivity was markedly attenuated in these brain regions when chylomicron formation/secretion was blocked by Pluronic L-81. After lymph was diverted from the lymph cannulated animals, the rats had a lower number of c-Fos-positive cells in the NTS and ARC. In contrast, the rats had higher c-Fos-positive neurons in PVN. The present study also revealed that c-Fos-positive neurons induced by feeding of Intalipid were abolished by CCK type 1 receptor antagonist, Lorglumide. We conclude that the formation and/or secretion of chylomicron are critical steps for initiating neuronal activation in the brain.

Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage

1997 ◽  
Vol 273 (1) ◽  
pp. E202-E206 ◽  
Author(s):  
R. Dawson ◽  
M. A. Pelleymounter ◽  
W. J. Millard ◽  
S. Liu ◽  
B. Eppler
Keyword(s):  
Weight Gain ◽  
Arcuate Nucleus ◽  
Body Weight Gain ◽  
Monosodium Glutamate ◽  
Anatomic Site ◽  
Leptin Receptors ◽  
Fat Depots ◽  
Mediated Effects ◽  
Night Feeding ◽  
Neonatal Administration

Leptin is a protein secreted by adipocytes that is important in regulating appetite and adiposity. Recent studies have suggested the presence of leptin receptors in the arcuate nucleus of the hypothalamus (ANH). Neonatal administration of monosodium glutamate (MSG) damages the ANH, resulting in obesity and neuroendocrine dysfunction. Neonatal administration of MSG was utilized to test the hypothesis that the anatomic site for many of leptin's actions is the ANH. Female control (n = 6) and MSG-treated rats (n = 7) were implanted for 14 days with osmotic minipumps containing phosphate-buffered saline or leptin (1 mg.kg-1.day-1). Leptin suppressed (P < 0.05) body weight gain in controls but did not suppress weight gain in MSG-treated rats. Leptin decreased (P < 0.05) fat depots in controls but had no effect in MSG-treated rats. Night feeding was suppressed (P < 0.05) in leptin-treated control rats. MSG-treated rats showed a suppression in food intake that was of a smaller magnitude and appeared later in the course of leptin treatment. These findings suggest that leptin mediates some physiological actions related to fat mobilization via receptors located in the ANH.

scholarly journals Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasis

2020 ◽  
Author(s):  
Juliana Bezerra Medeiros de Lima ◽  
Lucas Kniess Debarba ◽  
Manal Khan ◽  
Chidera Ubah ◽  
Olesya Didyuk ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Glucose Metabolism ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Brain Regions ◽  
Designer Drugs ◽  
Whole Body ◽  
Mouse Line ◽  
Hypothalamic Arcuate Nucleus

AbstractGrowth hormone (GH) receptor (GHR), expressed in different brain regions, is known to participate in the regulation of whole-body energy homeostasis and glucose metabolism. However, GH activation of these GHR-expressing neurons is less studied. We have generated a novel GHR-driven Cre recombinase transgenic mouse line (GHRcre) in combination with the floxed tdTomato reporter mouse line we tracked and activated GHR-expressing neurons in different regions of the brain. We focused on neurons of the hypothalamic arcuate nucleus (ARC) where GHR was shown to elicit a negative feedback loop that regulates GH production. We found that ARCGHR+ neurons are co-localized with AgRP, GHRH, and somatostatin neurons, which were activated by GH stimulation. Using designer receptors exclusively activated by designer drugs (DREADDs) to control GHRARC neuronal activity, we revealed that activation of GHRARC neurons was sufficient in regulating distinct aspects of energy balance and glucose metabolism. Overall, our study provides a novel mouse model to study in vivo regulation and physiological function of GHR-expressing neurons in various brain regions. Furthermore, we identified for the first time specific neuronal population that responds to GH and directly linked it to metabolic responses in vivo.

scholarly journals Ghrelin Stimulates GH But Not Food Intake in Arcuate Nucleus Ablated Rats

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3268-3275 ◽  
Author(s):  
Hideki Tamura ◽  
Jun Kamegai ◽  
Takako Shimizu ◽  
Shinya Ishii ◽  
Hitoshi Sugihara ◽  
...  
Keyword(s):  
Food Intake ◽  
Normal Control ◽  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Male Rats ◽  
Appetite Control ◽  
Gh Secretion ◽  
Increase Food Intake ◽  
Hypothalamic Arcuate Nucleus ◽  
Plasma Gh

Abstract Ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHS-R1a), was originally purified from the rat stomach. Ghrelin mRNA and peptide have also been detected in the hypothalamus and pituitary. Ghrelin is a novel acylated peptide that regulates GH release and energy metabolism. GHS-R1a mRNA is expressed in the pituitary gland as well as in several areas of the brain including the hypothalamus. In this study, we examined whether ghrelin could stimulate GH secretion and feeding in chronic GHRH, neuropeptide Y, and agouti-related protein deficient rats that were neonatally treated with monosodium glutamate (MSG), which destroys the neurons in the hypothalamic arcuate nucleus (ARC). Intravenous (iv) administration of rat ghrelin (10 μg/kg body weight) increased plasma GH levels significantly in the normal adult male rats during a GH trough period of pulsatile GH secretion, while iv injection of ghrelin in MSG-treated rats resulted in a markedly attenuated GH response. When rat ghrelin (10 μg/rat) was administered intracerebroventricular (icv), plasma GH levels were increased comparably in normal control and MSG-treated rats. However, the GH release after icv injection of ghrelin was markedly diminished compared with that after iv administration of a small amount of ghrelin in normal control rats (icv: 10 μg/rat, iv: approximately 4.0 μg/rat), indicating that the GH-releasing activity of exogenous ghrelin is route dependent and at least in part via hypothalamic ARC. The icv administration of 1 μg of ghrelin increased significantly 4-h food intake in normal control, whereas the peptide did not increase food intake in MSG-treated rats, indicating that the feeding response to ghrelin requires intact ARC. Taken together, the primary action of ghrelin on appetite control and GH releasing activity is via the ARC even though it might act on another type of GHS-R besides GHS-R1a.

Sign in / Sign up

Export Citation Format

Share Document