Mode of action of OB protein (leptin) on feeding

1998 ◽  
Vol 275 (1) ◽  
pp. R174-R179 ◽  
Author(s):  
Mark C. Flynn ◽  
Thomas R. Scott ◽  
Thomas C. Pritchard ◽  
Carlos R. Plata-Salamán
Keyword(s):  
Food Intake ◽  
Wistar Rats ◽  
Feeding Rate ◽  
Meal Size ◽  
Meal Frequency ◽  
Dependent Manner ◽  
Intracerebroventricular Administration ◽  
Ad Libitum ◽  
Ob Protein ◽  
Dose Dependent

OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56–3.5 μg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 μg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 μg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.

Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus

1998 ◽  
Vol 274 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
David S. Ludwig ◽  
Kathleen G. Mountjoy ◽  
Jeffrey B. Tatro ◽  
Jennifer A. Gillette ◽  
Robert C. Frederich ◽  
...  
Keyword(s):  
Food Intake ◽  
Mammalian Brain ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Intracerebroventricular Administration ◽  
Melanocyte Stimulating Hormone ◽  
Molar Excess ◽  
Melanin Concentrating Hormone ◽  
Skin Coloration ◽  
Dose Dependent

Melanin-concentrating hormone (MCH) and α-melanocyte-stimulating hormone (α-MSH) demonstrate opposite actions on skin coloration in teleost fish. Both peptides are present in the mammalian brain, although their specific physiological roles remain largely unknown. In this study, we examined the interactions between MCH and α-MSH after intracerebroventricular administration in rats. MCH increased food intake in a dose-dependent manner and lowered plasma glucocorticoid levels through a mechanism involving ACTH. In contrast, α-MSH decreased food intake and increased glucocorticoid levels. MCH, at a twofold molar excess, antagonized both actions of α-MSH. α-MSH, at a threefold molar excess, blocked the orexigenic properties of MCH. MCH did not block α-MSH binding or the ability of α-MSH to induce cAMP in cells expressing either the MC3 or MC4 receptor, the principal brain α-MSH receptor subtypes. These data suggest that MCH and α-MSH exert opposing and antagonistic influences on feeding behavior and the stress response and may function in a coordinate manner to regulate metabolism through a novel mechanism mediated in part by an MCH receptor.

The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size

2007 ◽  
Vol 293 (3) ◽  
pp. R983-R987 ◽  
Author(s):  
Karen A. Scott ◽  
Timothy H. Moran
Keyword(s):  
Food Intake ◽  
Rhesus Macaques ◽  
Specific Effect ◽  
Meal Size ◽  
Reduce Food Intake ◽  
Dependent Manner ◽  
Primate Model ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Dose Dependent

Exendin-4 (Ex4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and suppress gastric emptying in rodents and humans. In this study we investigated the effects of peripheral administration of Ex4 on food intake and meal patterns in adult male rhesus macaques. Rhesus macaques ( n = 4) that had been trained to lever press for food pellets were injected intramuscularly 15 min before the start of their 6-h daily feeding period. Ex4 was given at doses of 0.10, 0.32, 0.56, 1.0, and 3.0 μg/kg. Ex4 suppressed food intake in a dose-dependent manner, with the 3.0 μg/kg dose completely preventing feeding during the 6-h period and the 0.10 μg/kg dose suppressing intake by 17%. Doses of 0.32, 0.56, 1.0, and 3.0 μg/kg caused significant reductions in cumulative intake at all six hourly time points. Ex4 inhibited food intake through a specific effect on meal size. Meal size was significantly reduced in a dose-dependent manner with significant reductions at the 0.32 and 1.0 μg/kg doses ( P < 0.05). Day 2 and 3intakes returned to baseline levels with no compensation for Ex4-induced feeding suppression. Administration of doses of 0.32 and 0.56 μg/kg Ex4 over 5 consecutive days led to sustained reductions in intake with no evidence of compensation. Again, these reductions were due to specific effects on meal size. These results demonstrate that activation of GLP-1 pathways has potent effects on the controls of meal size and overall food intake in a nonhuman primate model.

Effects of duodenal and distal ileal infusions of glucose and oleic acid on meal patterns in rats

1995 ◽  
Vol 269 (1) ◽  
pp. R7-R14 ◽  
Author(s):  
T. Woltman ◽  
R. Reidelberger
Keyword(s):  
Oleic Acid ◽  
Dark Period ◽  
Meal Size ◽  
Meal Frequency ◽  
Meal Patterns ◽  
Distal Small Intestine ◽  
Ad Libitum ◽  
Dose Dependent ◽  
Ad Libitum Feeding ◽  
Cumulative Food Intake

The mechanisms mediating the anorexic effects of nutrients in the proximal and distal small intestine are not clearly understood. We determined the dose-dependent effects of duodenal and distal ileal infusions of glucose and oleic acid on meal patterns in ad libitum feeding rats. Rats with cannulas in both the duodenum and ileum received a 2-h infusion of glucose (0, 800, 1,600, 3,200, 6,400, or 12,800 mumol/h) or oleic acid (0, 48, 240, 640, or 1,280 mumol/h) into the duodenum or ileum at the start of the dark period, and meal patterns were monitored for 4 h. Cumulative food intake was inhibited dose dependently by ileal as well as duodenal infusion of both glucose and oleic acid. Ileal glucose was more inhibitory than duodenal glucose, whereas duodenal oleic acid was more inhibitory than ileal oleic acid. Duodenal glucose and oleic acid inhibited feeding by decreasing meal frequency; ileal oleic acid decreased only meal size, whereas ileal glucose reduced both meal size and frequency. We interpret these results to suggest that ileal oleic acid and glucose suppress feeding by different mechanisms and that these mechanisms differ from those mediating the anorexic responses to oleic acid and glucose in the duodenum.

Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats

1998 ◽  
Vol 275 (1) ◽  
pp. R180-R185 ◽  
Author(s):  
Andrea Kahler ◽  
Nori Geary ◽  
Lisa A. Eckel ◽  
L. Arthur Campfield ◽  
Françoise J. Smith ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Weight Gain ◽  
Chronic Administration ◽  
Meal Size ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Ad Libitum ◽  
Ob Protein

The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g (or 13–20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21–34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.

Prolactin stimulates food intake in a dose-dependent manner

1989 ◽  
Vol 256 (1) ◽  
pp. R276-R280 ◽  
Author(s):  
T. Gerardo-Gettens ◽  
B. J. Moore ◽  
J. S. Stern ◽  
B. A. Horwitz
Keyword(s):  
Food Intake ◽  
Female Rats ◽  
High Dose ◽  
Dependent Manner ◽  
Additional Control ◽  
The Mean ◽  
Ovine Prolactin ◽  
Dose Dependent ◽  
Medium Dose ◽  
Cumulative Food Intake

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.

scholarly journals Antidiarrheal Activity of Dissotis multiflora (Sm) Triana (Melastomataceae) Leaf Extract in Wistar Rats and Subacute Toxicity Evaluation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Alian Désiré Afagnigni ◽  
Maximilienne Ascension Nyegue ◽  
Chantal Florentine Ndoye Foe ◽  
Youchahou Njankouo Ndam ◽  
Frédéric Nico Njayou ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Leaf Extract ◽  
Shigella Flexneri ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Subacute Toxicity ◽  
Antidiarrheal Activity ◽  
Dose Dependent ◽  
Ethanolic Leaf Extract

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days’ subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased (p<0.05) in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease (p<0.05) of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.

Effects of meal frequency on energy utilization in rats

1988 ◽  
Vol 255 (4) ◽  
pp. R616-R621 ◽  
Author(s):  
J. O. Hill ◽  
J. C. Anderson ◽  
D. Lin ◽  
F. Yakubu
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Energy Utilization ◽  
Male Rats ◽  
Major Influence ◽  
Meal Frequency ◽  
Ad Libitum

The effects of differences in meal frequency on body weight, body composition, and energy expenditure were studied in mildly food-restricted male rats. Two groups were fed approximately 80% of usual food intake (as periodically determined in a group of ad libitum fed controls) for 131 days. One group received all of its food in 2 meals/day and the other received all of its food in 10-12 meals/day. The two groups did not differ in food intake, body weight, body composition, food efficiency (carcass energy gain per amount of food eaten), or energy expenditure at any time during the study. Both food-restricted groups had a lower food intake, body weight gain, and energy expenditure than a group of ad libitum-fed controls. In conclusion, these results suggest that amount of food eaten, but not the pattern with which it is ingested, has a major influence on energy balance during mild food restriction.

Food intake response to modulation of secretion of cholecystokinin in Zucker rats

1983 ◽  
Vol 244 (5) ◽  
pp. R676-R685 ◽  
Author(s):  
C. L. McLaughlin ◽  
S. R. Peikin ◽  
C. A. Baile
Keyword(s):  
Food Intake ◽  
Negative Feedback ◽  
Pancreatic Enzyme ◽  
Meal Size ◽  
Zucker Rats ◽  
Feedback Signal ◽  
Meal Frequency ◽  
Feeding Behaviors ◽  
Endogenous Release ◽  
Cck Release

Exogenous administration of cholecystokinin (CCK) decreases food intake and elicits satiety behaviors. In the present experiments, feeding behaviors of Zucker obese and lean rats were measured in response to treatments that influence endogenous secretion of CCK from the duodenum. Secretion of CCK was increased by administration of phenylalanine, a stimulant of CCK release, and of trypsin inhibitor, which binds to trypsin, a negative-feedback signal for CCK release. Both of these treatments decreased the size of the first meal after a 6-h fast and average daily meal size and increased meal frequency. Administration of trypsin, proported to decrease secretion of CCK, increased average daily meal size and decreased meal frequency. Pancrease, a pancreatic enzyme concentrate, also hypothesized to act as a negative-feedback signal for CCK release, elicited feeding behaviors similar to those of trypsin. Thus the effects of these compounds on the feeding behavior of Zucker obese and lean rats may be related to their effects on CCK secretion. The feeding behaviors of obese rats were affected less than those of lean rats by exogenous administration of CCK, but in these experiments were affected more than in lean rats by modulation of endogenous release of CCK.

scholarly journals ANTI-DIABETIC EFFECT OF A NOVEL NANO POLYMER OF THYMOL IN STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS

2019 ◽  
pp. 81-89
Author(s):  
ELAHE KARIMI ◽  
SHAHRYAR ABBASI ◽  
ALI AIDY ◽  
HORI GHANEIALVAR ◽  
SHAHRAM MOHAMMADPOUR ◽  
...  
Keyword(s):  
Animal Model ◽  
Biochemical Parameters ◽  
Wistar Rats ◽  
Liver Enzymes ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Elisa Kit ◽  
Blood Biochemical ◽  
Dose Dependent

Objective: The aim of this study was to evaluate the effect of thymol and thymol nano polymer on the blood biochemical parameters and anti-diabetic activity in Streptozotocin (STZ)-induced diabetic rats. Methods: The synthesized nano polymer (NP) was characterized by using different spectroscopy methods, such as IR, HNMR and CNMR. Loading and releasing of thymol were investigated by HPLC. Eleven groups of the Streptozotocin-induced diabetic and normal rats (overall 110 males) were tested through various biochemical factors such as: serum glucose, insulin, liver function-related enzymes including ALT, AST, ALP and bilirubin by ELISA kit methods. Results: It has shown that thymol nano polymer is desirable for transferring drug. The amount of thymol loaded on NP estimated at 43±2.5 %. Then, 65% of the loaded drug was released. LD50 for thymol and thymol nano polymer were 435 and 583 mg/kg, respectively. thymol nano polymer at doses of 30, 60 and 90 mg/kg, in a dose-dependent manner, reduced blood glucose, increased insulin levels, and controlled liver enzymes ALT, AST, ALP and bilirubin in the STZ-induced diabetic rats. Conclusion: The use of thymol nano polymer appears to be a new aspect concerning to protect diabetes-induced damage in the animal model.

scholarly journals Amylin receptor blockade stimulates food intake in rats

2004 ◽  
Vol 287 (3) ◽  
pp. R568-R574 ◽  
Author(s):  
Roger D. Reidelberger ◽  
Alvin C. Haver ◽  
Urban Arnelo ◽  
D. David Smith ◽  
Courtney S. Schaffert ◽  
...  
Keyword(s):  
Food Intake ◽  
Intravenous Infusion ◽  
Liquid Diet ◽  
Meal Size ◽  
Meal Frequency ◽  
Energy Reserves ◽  
Selective Blockade ◽  
Inhibit Food Intake ◽  
Hormonal Signal ◽  
The Brain

Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves. Amylin potently reduces food intake, body weight, and adiposity when administered systemically or into the brain. Whether selective blockade of endogenous amylin action increases food intake and adiposity remains to be clearly established. In the present study, the amylin receptor antagonist acetyl-[Asn30, Tyr32] sCT-( 8 – 32 ) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur. Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60–2,000 pmol·kg−1·min−1), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol·kg−1·min−1) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h). Infusions began just before dark onset. Food intake and meal patterns during the first 4 h of the dark period were determined from continuous computer recordings of changes in food bowl weight. Amylin inhibited food intake by ∼50%, and AC187 attenuated this response by ∼50%. AC187 dose-dependently stimulated food intake (maximal increases from 76 to 171%), whether administered alone or with an intragastric infusion of liquid diet. Amylin reduced mean meal size and meal frequency, AC187 attenuated these responses, and AC187 administration alone increased mean meal size and meal frequency. These results support the hypothesis that endogenous amylin plays an essential role in reducing meal size and increasing the postmeal interval of satiety.

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