Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control

1996 ◽  
Vol 270 (2) ◽  
pp. R443-R449 ◽  
Author(s):  
B. G. Stanley ◽  
V. L. Willett ◽  
H. W. Donias ◽  
M. G. Dee ◽  
M. A. Duva
Keyword(s):  
Body Weight ◽  
Nmda Receptors ◽  
Kainic Acid ◽  
Weight Control ◽  
Body Weight Loss ◽  
Nmda Antagonist ◽  
Male Rats ◽  
Long Term Effects ◽  
Lateral Hypothalamic ◽  
Daily Food

To determine whether endogenous lateral hypothalamic (LH) glutamate and its N-methyl-D-aspartate (NMDA) receptors might participate in the stimulation of natural eating, LH injection of the NMDA antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was tested in adult male rats for suppressive actions on feeding elicited by 1) NMDA, kainic acid or D, L-alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) injected into the LH; 2) food deprivation; and 3) the onset of the nocturnal period. D-AP5 (10-100 nmol) reduced by 72-90% the approximately 10-g eating response elicited by NMDA (10 nmol) without affecting the quantitatively similar eating responses elicited by kainic acid (1.0 nmol) or AMPA (1.0 nmol). This treatment also suppressed deprivation-induced eating by as much as 61% and nocturnal eating by as much as 40%. To determine its long-term effects, D-AP5 (50 nmol) was injected bilaterally into the LH twice a day for 8 consecutive days. This treatment caused up to 65% reductions in daily food intake and body weight loss of up to 13 g/day. These findings, showing behaviorally selective suppressions of eating and body weight by D-AP5, argue that endogenous LH glutamate acts to regulate natural eating and body weight and that NMDA receptors participate in these functions.

Influence of long-term exposure to adverse environments on organ weights and histology

1959 ◽  
Vol 196 (3) ◽  
pp. 520-524 ◽  
Author(s):  
Henry B. Hale ◽  
Roy B. Mefferd ◽  
Gordon Vawter ◽  
G. Elizabeth Foerster ◽  
Dominic Criscuolo
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Body Weight Loss ◽  
Male Rats ◽  
Temperature Dependency ◽  
Organ Weights ◽  
Thymus Weight ◽  
Pressure Dependency ◽  
Liver And Kidney ◽  
Induced Changes

A comparison was made of the morphological effects of cold, heat and simulated altitude on adult male rats given exposures of 24 weeks' duration. By the use of covariance analysis it was possible to determine the extent to which organ weights were dependent upon body weight and to adjust the values in order to remove body weight influences. For liver, heart and kidney, adjusted weights indicated temperature-dependency, while pressure-dependency was established for liver and kidney only. Histologically, temperature-dependency was indicated for liver, kidney, thyroid, adrenal and pituitary. Fur weight was reduced in heat but not altered in cold. Fasting in cold induced changes in adrenal and thymus weight and unusually high body weight loss; in heat, fasting caused a significant thymus weight loss without adrenal weight increase. The thymus-adrenal ratio was elevated during a 24-hour fast in all environments except cold, where it was decreased.

A long-term high-protein diet markedly reduces adipose tissue without major side effects in Wistar male rats

2004 ◽  
Vol 287 (4) ◽  
pp. R934-R942 ◽  
Author(s):  
Magali Lacroix ◽  
Claire Gaudichon ◽  
Antoine Martin ◽  
Céline Morens ◽  
Véronique Mathé ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Control ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Male Rats ◽  
Calcium Balance ◽  
Long Term Effects ◽  
Wistar Male Rats

Although there is a considerable interest of high-protein, low-carbohydrate diets to manage weight control, their safety is still the subject of considerable debate. They are suspected to be detrimental to the renal and hepatic functions, calcium balance, and insulin sensitivity. However, the long-term effects of a high-protein diet on a broad range of parameters have not been investigated. We studied the effects of a high-protein diet in rats over a period of 6 mo. Forty-eight Wistar male rats received either a normal-protein (NP: 14% protein) or high-protein (HP: 50% protein) diet. Detailed body composition, plasma hormones and nutrients, liver and kidney histopathology, hepatic markers of oxidative stress and detoxification, and the calcium balance were investigated. No major alterations of the liver and kidneys were found in HP rats, whereas NP rats exhibited massive hepatic steatosis. The calcium balance was unchanged, and detoxification markers (GSH and GST) were enhanced moderately in the HP group. In contrast, HP rats showed a sharp reduction in white adipose tissue and lower basal concentrations of triglycerides, glucose, leptin, and insulin. Our study suggests that the long-term consumption of an HP diet in male rats has no deleterious effects and could prevent metabolic syndrome.

scholarly journals Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats

2015 ◽  
Vol 308 (1) ◽  
pp. E40-E50 ◽  
Author(s):  
Beatriz de Carvalho Borges ◽  
Rodrigo C. Rorato ◽  
Ernane Torres Uchoa ◽  
Paula B. Marangon ◽  
Carol F. Elias ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Tyrosine Phosphatase ◽  
Body Weight Loss ◽  
Male Rats ◽  
Leptin Resistance ◽  
Reduce Food Intake ◽  
Low Grade ◽  
Lps Treatment

Leptin resistance is induced by the feedback inhibitors tyrosine phosphatase-1B (PTP1B) and decreased Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) signaling. To investigate the participation of PTP1B and SHP-2 in LPS-induced leptin resistance, we injected repeated (6-LPS) intraperitoneal LPS doses (100 μg/kg ip) for comparison with a single (1-LPS) treatment and evaluated the expression of SHP-2, PTP1B, p-ERK1/2, and p-STAT3 in the hypothalamus of male Wistar rats. The single LPS treatment increased the expression of p-STAT3 and PTP1B but not SHP-2. The repeated LPS treatment reduced SHP-2, increased PTP1B, and did not change p-STAT3. We observed that the PTP1B expression induced by the endotoxin was highly colocalized with leptin receptor cells in the hypothalamus of LepRb-IRES-Cre-tdTomato reporter mice. The single, but not the repeated, LPS treatment decreased the food intake and body weight. Leptin had no stimulatory effect on the hypophagia, body weight loss, or pSTAT3 expression in 6-LPS rats, indicating leptin unresponsiveness. Notably, the PTP1B inhibitor (3.0 nmol/rat in 5 μl icv) restored the LPS-induced hypophagia in 6-LPS rats and restored the ability of leptin to reduce food intake and body weight as well as to phosphorylate STAT3 in the arcuate, paraventricular, and ventromedial nuclei of the hypothalamus. The present data suggest that an increased PTP1B expression in the hypothalamus underlies the development of leptin resistance during repeated exposure to LPS. Our findings contribute to understanding the mechanisms involved in leptin resistance during low-grade inflammation as seen in obesity.

Diet and body weight loss in the rat during calorie restriction

1968 ◽  
Vol 46 (1) ◽  
pp. 101-107
Author(s):  
Peter B. Karch ◽  
John R. Beaton
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Body Fat ◽  
Resting Metabolic Rate ◽  
Urine Volume ◽  
Body Weight Loss ◽  
The Body ◽  
Male Rats ◽  
Calorie Intake ◽  
Isocaloric Diets

With adult male rats, experiments were carried out to ascertain the different effects, if any, of isocaloric diets high in carbohydrate, fat, or protein fed in restricted amounts of 9 g per rat per day on body weight loss and composition. It was observed that the nature of the diet did not alter rate, amount, or composition of body weight loss when fed in restricted amount for a period of 12 days. Further, the nature of the diet did not alter significantly the following parameters during restriction: water intake, urine volume, resting metabolic rate, spontaneous activity, urine and feces calorie values. In an experiment with hypothalamic-obese rats, the body weight loss and composition were not significantly different among the dietary-restricted groups. An important observation in this experiment was that as body fat decreased markedly owing to restricted feeding, body water increased markedly and counterbalanced approximately 60% of the potential weight loss due to the decrease in body fat. Our reported observations do not support the hypothesis that the composition of the diet may determine the rate and amount of body weight loss as a consequence of restricted food intake. They do support the hypothesis that the calorie intake, not the nature of the source of calories, determines the rate and amount of weight loss, at least for relatively short periods of food restriction.

scholarly journals Endogenous loss of leucine and methionine in adult male rats

1977 ◽  
Vol 37 (2) ◽  
pp. 259-268 ◽  
Author(s):  
R. J. Neale ◽  
J. C. Waterlow
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Amino Acid ◽  
Adult Male ◽  
Body Weight Loss ◽  
Male Rats ◽  
Fractional Rate ◽  
Low Protein ◽  
Total Body ◽  
Fractional Loss

1. The fractional rate of loss of 14C and body-weight was measured in adult male rats after giving 14C-labelled methionine or leucine and maintaining rats for 30 d on a low-protein or a specific methionine+cystine-free diet: carcasses were then analysed for protein and fat 14C radioactivity.2. The fractional loss of 14CO2 from [14C]methionine or [14C]leucine between day 20 and day 30 was always greater than the fractional loss of body-weight.3. Carcass protein 14C radioactivity after giving [14C]leucine was higher than after giving [14C]methionine, but fat 14C radioactivity after either 14C-labelled amino acid was only a small proportion of the total body 14C radioactivity.4. After correction of the fractional loss of 14CO2 for urinary 14C loss, but not body-weight loss, absolute amino acid loss was calculated using published values for methionine and leucine content of rats.5. The best estimates of endogenous amino acid loss obtained using 1-14C-labelled amino acids, expressed as mg/kg body-weight0.75 per day were leucine 79, methionine 38.

scholarly journals The toxicity of the technical product, derived triazolinones

2020 ◽  
Vol 64 (2) ◽  
pp. 83-87 ◽  
Author(s):  
Valery N. Rakitskii ◽  
E.G. Chkhvirkiya ◽  
T.M. Epishina
Keyword(s):  
Body Weight ◽  
Hematological Parameters ◽  
Oral Intake ◽  
Total Activity ◽  
The Body ◽  
Male Rats ◽  
Control Group ◽  
Long Term Effects ◽  
Technical Product

Introduction. Technical products that are part of pesticides recommended for use in agriculture must undergo a comprehensive sanitary and Toxicological examination, which is the basis for preventing the adverse effects of pesticides on the health of workers and the population, as well as on the sanitary state of the environment. Purpose of research - the study of the biological effect of the technical product derived triazolinthionov, with its repeated oral intake in mammals (rats), justification of the permissible daily dose (DSD) for humans. Material and methods. Chronic (12 months) experiment was conducted on male rats with a body weight of 200-210 g tested doses: 5.0; 50.0 and 500.0 mg/kg body weight (1 control and 3 experimental groups and 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water and food consumption, fixed the timing of death, recorded changes in body weight, physiological, biochemical and hematological parameters. Results. It was found that the dose of 5.0 mg/kg body weight does not cause significant changes in all studied parameters, doses of 50.0 and 500.0 mg/kg body weight had a polytropic effect on the body of experimental animals. Discussion. The studied technical product at repeated intake in doses of 50,0 and 500,0 mg/kg of body weight causes changes in the state of the Central nervous system of animals (statistically significant changes in SPP, total activity, path length, rest time), as well as changes in carbohydrate, lipid, and lipoprotein metabolism in the body, as evidenced by statistically significant changes in biochemical and hematological indicators. Consequently, doses of 50,0 and 500,0 mg/kg of body weight have a polytropic effect on the body of male rats and are effective. The dose of 5.0 mg/kg of body weight, when administered in animals of the experimental group in comparison with animals of the control group, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. On the basis of an inactive dose of 5.0 mg/kg of body weight and a reserve factor of 100, we have scientifically justified DSD for humans at the level of 0.05 mg/kg. Conclusion. Studies have shown that long-term repeated oral administration of the studied product into the body of animals (male rats) at a dose of 5.0 mg per 1 kg of body weight does not cause statistically significant changes in all the studied parameters, so the indicated dose is invalid. Doses of 50,0 and 500,0 mg/kg MT have a polytropic effect on the body of male rats and are effective. DSD for humans at the level of 0.05 mg/kg is justified based on the inactive dose at the level of 5.0 mg per 1 kg of body weight, established in a 12-month chronic experiment conducted on male rats, and the reserve coefficient of 100 (taking into account the unexpressed specific and long-term effects).

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