Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP

1996 ◽  
Vol 271 (1) ◽  
pp. R180-R184 ◽  
Author(s):  
E. E. Ladenheim ◽  
J. E. Taylor ◽  
D. H. Coy ◽  
K. A. Moore ◽  
T. H. Moran

Bombesin (BN)-like peptides injected peripherally or centrally suppress food intake in rats. The relationship between the central and peripheral actions of BN is unknown. However, experimental evidence supports a critical role for the caudal hindbrain in mediating the feeding effects of BN. To investigate this relationship further, we examined the ability of fourth ventricular infusion of a specific gastrin-releasing peptide (GRP) antagonist, [D-F5, Phe6, D-Ala11]BN-(6-13) methyl ester (BN-ME), to block suppression of glucose intake (0.5 kcal/ml) produced by intraperitoneal administration of GRP-(18-27) in 5-h food-deprived male Sprague-Dawley rats (n = 10). We found that fourth ventricular administration of 10, 32, and 100 ng BN-ME blocked the suppression of glucose intake produced by peripherally administered 10 nmol/kg GRP-(18-27). The most effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of GRP-(18-27) to inhibit glucose intake but had no effect on intake when given alone. These results demonstrate that the availability of caudal hindbrain GRP receptors is necessary for peripherally administered GRP-(18-27) to reduce food intake in rats.

2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.


1999 ◽  
Vol 276 (6) ◽  
pp. R1623-R1629 ◽  
Author(s):  
Gary J. Schwartz ◽  
Cynthia F. Salorio ◽  
Chris Skoglund ◽  
Timothy H. Moran

Subdiaphragmatic vagal afferent (SVA) signals arising from gut sites may provide critical feedback for the control of food intake within a meal. To evaluate the role of SVAs in both spontaneous and scheduled meals, food intake was assessed in two paradigms in male Sprague-Dawley rats. In the first study, control (Con) rats ( n = 6) and rats with subdiaphragmatic vagal deafferentation (SDA) ( n = 7) had 12-h nightly access to Ensure liquid diet (1 kcal/ml). SDA rats had larger and fewer meals and maintained initial rapid rates of licking, yet total numbers of licks were unaffected. In the second study, Con ( n = 8) and SDA ( n = 7) rats had scheduled access to 12.5% liquid glucose after overnight food deprivation. Glucose intake was assessed after 5-ml gastric preloads of 0.9% saline or glucose, peptone, and Intralipid solutions at three concentrations (0.5, 1, and 2 kcal/ml). Glucose and peptone preloads suppressed intake similarly in Con and SDA rats, whereas Intralipid was ineffective. These results suggest that meal-related SVA signals 1) are not critical in determining preload-induced feeding suppression after deprivation, yet 2) contribute to satiety during spontaneous meals.


1996 ◽  
Vol 271 (6) ◽  
pp. R1638-R1642 ◽  
Author(s):  
M. Monda ◽  
A. Sullo ◽  
E. De Luca ◽  
M. P. Pellicano

These experiments test the effect of intraperitoneal injection of lysine acetylsalicylate on 1) food intake and 2) the sympathetic and thermogenic changes induced by lesion of the lateral hypothalamus (LH). Food intake, firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), and IBAT and colonic temperatures (TIBAT and TC) were monitored in male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after intraperitoneal injection of lysine acetylsalicylate. The same variables were also monitored in 1) lesioned rats with intraperitoneal administration of saline, 2) sham-lesioned animals with intraperitoneal injection of lysine acetylsalicylate, and 3) sham-lesioned rats with intraperitoneal injection of saline. The results show that lysine acetylsalicylate modifies the aphagia by increasing food intake and also reduces the enhancements in firing rate, TIBAT, and TC induced by LH lesion. These findings suggest that prostaglandin synthesis plays a key role in the control of eating behavior in LH-lesioned rats by acting on the sympathetic and thermogenic changes induced by LH lesion.


1998 ◽  
Vol 275 (2) ◽  
pp. R384-R389 ◽  
Author(s):  
M. H. Porter ◽  
B. J. Hrupka ◽  
W. Langhans ◽  
G. J. Schwartz

We investigated the extrinsic gut neural mediation of the suppression of food intake in male Sprague-Dawley rats induced by peripheral intraperitoneal administration of 2 μg/kg interleukin-1β (IL-1β), 100 μg/kg bacterial lipopolysaccharide (LPS), and 2 mg/kg muramyl dipeptide (MDP). Food intake during the first 3 and 6 h of the dark cycle was measured in rats with subdiaphragmatic vagal deafferentation ( n = 9), celiac superior mesenteric ganglionectomy ( n = 9), combined vagotomy and ganglionectomy ( n = 9), and sham deafferentation ( n = 9). IL-1β, LPS, and MDP suppressed food intake at 3 and 6 h in all surgical groups. The results demonstrate that neither vagal nor nonvagal afferent nerves from the upper gut are necessary for the feeding-suppressive effects of intraperitoneal IL-1β, LPS, or MDP in the rat and suggest that peripheral administration of immunomodulators produces anorexia via a humoral pathway.


Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.


1982 ◽  
Vol 243 (1) ◽  
pp. R60-R64 ◽  
Author(s):  
R. L. Atkinson ◽  
E. L. Brent

Male Sprague-Dawley rats with a jejunoileal bypass ate 32% less in the 1st h of refeeding after an overnight fast than did sham-bypass rats. Fasted recipients injected intraperitoneally with 6-7 ml of bypass plasma also ate 32% less (P less than 0.001) during the 1st h of refeeding than did recipients of sham-bypass plasma, but subsequent intake was not significantly different. Rectal temperature, hematocrit, white blood cell count, and percent polymorphonuclear leukocytes were not different between bypass and sham-bypass rats. A test for aversive conditioning suggested that the effect of bypass plasma was not due to illness or discomfort. These data suggest that intestinal bypass produces a transferable humoral factor that suppresses food intake and that the effect is not due to illness or discomfort. If the decreased food intake in humans after intestinal bypass is due to a similar mechanism, the possibility exists that this humoral appetite-suppressant factor may be clinically useful in the treatment of morbid obesity.


2021 ◽  
Vol 10 ◽  
Author(s):  
Kazunari Kadokura ◽  
Tsuyoshi Tomita ◽  
Kohei Suruga

Abstract The fish paste product, fish balls ‘tsumire’, is a traditional type of Japanese food made from minced fish as well as imitation crab, kamaboko and hanpen. Although tsumire is known as a high-protein and low-fat food, there is a lack of scientific evidence on its health benefits. Hence, we aimed to investigate the effects of tsumire intake on organ weight and biomarker levels in Sprague–Dawley rats for 84 d as a preliminary study. Six-week-old male Sprague–Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5 % dried tsumire. Throughout the administration period, we monitored their body weight and food intake; at the end of this period, we measured their organ weight and analysed their blood biochemistry. No significant differences were observed with respect to body weight, food intake, organ weight and many biochemical parameters between the two groups. It was found that inorganic phosphorus and glucose levels were higher in group II rats than in group I rats. On the other hand, sodium, calcium, amylase and cholinesterase levels were significantly lower in group II than in group I. Interestingly, we found that the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase and leucine aminopeptidase in group II were significantly lower than in group I, and that other liver function parameters of group II tended to be lower than in group I. In conclusion, we consider that the Japanese traditional food, ‘tsumire,’ may be effective as a functional food for human health management worldwide.


2008 ◽  
Vol 1 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Samir G. Sukkar ◽  
Franca Cella ◽  
Stefania Patriarca ◽  
Anna L. Furfaro ◽  
Francesca Abate ◽  
...  

2000 ◽  
Vol 278 (2) ◽  
pp. R499-R503 ◽  
Author(s):  
C. M. Kotz ◽  
M. J. Glass ◽  
A. S. Levine ◽  
C. J. Billington

Naltrexone (NLTX) in the nucleus of the solitary tract (NTS) decreases feeding induced by neuropeptide Y (NPY) in the paraventricular nucleus (PVN). We sought to determine the NTS region most sensitive to NLTX blockade of PVN NPY-induced feeding. Male Sprague-Dawley rats were fitted with two cannulas; one in the PVN and one in a hindbrain region: caudal, medial, or rostral NTS or 1 mm outside the NTS. Animals received NLTX (0, 1, 3, 10, and 30 μg in 0.3 μl) into the hindbrain region just prior to PVN NPY (0.5 μg, 0.3 μl) or artificial cerebrospinal fluid (0.3 μl). Food intake was measured at 2 h following injection. PVN NPY stimulated feeding, and NLTX in the medial NTS significantly decreased NPY-induced feeding at 2 h, whereas administration of NLTX in the other hindbrain regions did not significantly influence PVN NPY induced feeding. These data suggest that opioid receptors in the medial NTS are most responsive to feeding signals originating in the PVN after NPY stimulation.


2000 ◽  
Vol 279 (1) ◽  
pp. R230-R238 ◽  
Author(s):  
Clayton E. Mathews ◽  
Kathie Wickwire ◽  
Wiliam P. Flatt ◽  
Carolyn D. Berdanier

The hypothesis that BHE/Cdb rats with mutations in their mitochondrial genome might accommodate this mutation by changing their food intake patterns was tested. Four experiments were conducted. Experiments 1 and 2examined food intake patterns of BHE/Cdb rats fed a stock diet or BHE/Cdb and Sprague-Dawley rats fed a high-fat diet from weaning. Experiment 3 examined the daily rhythms of respiration and heat production in these rats at 200 days of age. Experiment 4 examined the effects of diet composition on these measurements at 50-day intervals. The Sprague-Dawley rats, regardless of diet, had the typical day-night rhythms of feeding and respiration. In contrast, the BHE/Cdb rats fed the high-fat diet showed normal rhythms initially, but with age, these rhythms were attenuated. The changes in rhythms preceded the development of glucose intolerance.


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