Fourth ventricle bombesin injection suppresses ingestive behaviors in rats

1989 ◽  
Vol 256 (3) ◽  
pp. R590-R596 ◽  
Author(s):  
F. W. Flynn

Food intake after fourth intracerebroventricular (icv) injections of bombesin (BBS) was measured in intact rats. BBS injections (greater than or equal to 10 ng) reliably suppressed chow intake in 17-h food-deprived rats. Systemic injections of BBS (50 ng) had no effect on food intake. These data indicate that BBS can act directly on caudal brain stem site(s) to inhibit food intake. The behavioral specificity of fourth icv BBS was evaluated by measuring the effects of fourth icv BBS injection on water intake by 17-h water-deprived rats in the presence and absence of food. Fourth icv injections of BBS in doses greater than 10 ng suppressed 30-min and 2-h water intake relative to saline injection when food was available in the home cage. In contrast, when food was not present during the 2-h intake test, fourth icv injections of BBS had no effect on water intake. This suggests that the inhibition of water intake was secondary to the effects of BBS on food intake. Lastly, sucrose (0.1 M) was paired with fourth icv BBS (50 ng), fourth icv saline, and intraperitoneal LiCl (1.5 meq/kg) in three groups of naive rats, and sucrose preference was subsequently measured. Rats that received injections of either saline or BBS preferred sucrose during the 24-h two-bottle test, and their preference ratios were significantly greater than those of the LiCl-injected rats. The role of afferent signals elicited by fourth ventricle BBS administration in the control of food intake is discussed.

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3101-3109 ◽  
Author(s):  
Andrea Peier ◽  
Jennifer Kosinski ◽  
Kimberly Cox-York ◽  
Ying Qian ◽  
Kunal Desai ◽  
...  

Neuromedin U (NMU) and neuromedin S (NMS) are structurally related neuropeptides that have been reported to modulate energy homeostasis. Pharmacological data have shown that NMU and NMS inhibit food intake when administered centrally and that NMU increases energy expenditure. Additionally, NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU are lean and hypophagic. Two high-affinity NMU/NMS receptors, NMUR1 and NMUR2, have been identified. NMUR1 is predominantly expressed in the periphery, whereas NMUR2 is predominantly expressed in the brain, suggesting that the effects of centrally administered NMU and NMS are mediated by NMUR2. To evaluate the role of NMUR2 in the regulation of energy homeostasis, we characterized NMUR2-deficient (Nmur2−/−) mice. Nmur2−/− mice exhibited a modest resistance to diet-induced obesity that was at least in part due to reduced food intake. Acute central administration of NMU and NMS reduced food intake in wild-type but not in Nmur2−/− mice. The effects on activity and core temperature induced by centrally administered NMU were also absent in Nmur2−/− mice. Moreover, chronic central administration of NMU and NMS evoked significant reductions in body weight and sustained reductions in food intake in mice. In contrast, Nmur2−/− mice were largely resistant to these effects. Collectively, these data demonstrate that the anorectic and weight-reducing actions of centrally administered NMU and NMS are mediated predominantly by NMUR2, suggesting that NMUR2-selective agonists may be useful for the treatment of obesity.


1984 ◽  
Vol 246 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
M. F. Dallman

The relationships among food intake, insulin secretion, and adrenocortical function are reviewed. It is hypothesized that a major role of structures in, or passing through, the ventromedial hypothalamus is to inhibit food intake, insulin secretion, and adrenocortical function during the day (in the nocturnally active rat) and that this activity is normally driven by elements within the suprachiasmatic nuclei. Lesions of the ventromedial hypothalamus of rats result in nonrhythmic food intake, hyperinsulinemia, nonrhythmic adrenocortical function, and obesity. Adrenalectomy prevents or reverses the effects of lesions of the ventromedial hypothalamus on food intake, insulin secretion, and obesity, and corticosteroid replacement restores them. Because the actions of corticosteroids are both time- and dose-dependent, it is proposed that the effects of the tonic levels of corticosteroids observed after lesions of the ventromedial hypothalamus are to augment the hyperphagia, hyperinsulinemia, and substrate flow into fat to a greater extent than would occur if there were a normal circadian rhythm in adrenocortical function.


1994 ◽  
Vol 72 (8) ◽  
pp. 841-848 ◽  
Author(s):  
G. Harvey Anderson ◽  
Shuqin Luo ◽  
Leonidas Trigazis ◽  
Greta Kubis ◽  
Edmund T. S. Li

This study examined the effects of selected groups of essential amino acids (EAAs), given by gavage, on short-term food and water intake. Amino acid groups were selected on the basis of their common physiologic functions in relation to current hypotheses on the role of amino acids in food intake control, and the quantities given were based on the proportions in 1.5 g of the EAA content of albumin. The complete EAA mixture (1.5 g) suppressed food intake by an average of 60 and 37% during the 1st and 2nd h of feeding, respectively, but had no influence on feeding in the subsequent 12 h. Total daily (14 h) intake was decreased by 9%. With the exception of the aromatic amino acid (Phe + Tyr + Trp, 0.34 g) group, all groups significantly decreased food intake by a comparable magnitude (32%) during the 1st h. In this time period, rats given the EAAs, Arg + Met + Val (0.38 g), and Arg + His + Lys (0.44 g) mixtures increased their water intake, whereas intake by rats given the Phe + Tyr + Trp + Thr (0.46 g) and Ile + Leu + Val (0.45 g) mixtures was unchanged. Thus, the food intake suppression caused by EAAs was not accounted for by an equal effect of its component amino acid groups. As well, food intake suppression by amino acid groups was not explained by increased water consumption, nor was it simply related to the quantity of nitrogen provided by the treatment.Key words: food intake, water intake, essential amino acids.


1997 ◽  
Vol 272 (4) ◽  
pp. R1170-R1177 ◽  
Author(s):  
M. D. Rodriguez ◽  
T. J. Kalogeris ◽  
X. L. Wang ◽  
R. Wolf ◽  
P. Tso

To further investigate the possible role of apolipoprotein A-IV (apo A-IV) in the short-term control of food intake, we examined the kinetics of intestinal apo A-IV synthesis and release into lymph and plasma after intragastric delivery of physiological amounts of lipid. Within 30 min of intragastric administration of 0.1 g of triglyceride, plasma and lymph levels of apo A-IV were similar to those produced by exogenous apo A-IV that inhibit food intake. Within 15 min, 5% of gastrically delivered radioactive lipid reached the distal small bowel and cecum; by 30 min radioactivity was evenly distributed throughout the small intestine, with 10-15% of the load in the distal gut. By 30 min, synthesis of apo A-IV was significantly stimulated in proximal and distal jejunum and distal ileum and remained elevated up to 4 h after the delivery of lipid. Our results indicate that the delivery of physiological amounts of lipid into the stomach produces a significant and rapid stimulation of apo A-IV secretion into lymph and plasma, together with a rapid delivery of lipid and increases in mucosal synthesis of apo A-IV along the entire length of the small intestine. The results support a possible role for apo A-IV in the short-term control of food intake and suggest a role for the entire gut in the integrative response of apo A-IV to a fat meal.


2000 ◽  
Vol 278 (1) ◽  
pp. R50-R59 ◽  
Author(s):  
John G. Hohmann ◽  
Thomas H. Teal ◽  
Donald K. Clifton ◽  
James Davis ◽  
Victor J. Hruby ◽  
...  

Leptin serves as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to act through melanocortinergic pathways in the brain to regulate ingestive behaviors; however, whether melanocortins mediate leptin's actions on the neuroendocrine-reproductive axis is unknown. We tested this hypothesis first by determining whether the effects of leptin on feeding behavior and reproduction in the ob/ob mouse could be blocked by the melanocortin receptor (MC-R) antagonist SHU9119 and second, by examining the effects of the MC-R agonist MTII on feeding and the endocrine-reproductive system. Administered by intracerebroventricular injections, leptin inhibited food intake, raised plasma gonadotropin levels, and increased seminal vesicle weights compared with controls; SHU9119 (intracerebroventricularly) attenuated leptin's effects on food intake and body weight but did not alter leptin's stimulatory effect on the reproductive axis. MTII (intracerebroventricularly and intraperitoneally) decreased food intake and increased body temperature compared with controls but had no effect on the reproductive-endocrine axis. These results suggest that although leptin acts centrally through melanocortinergic pathways to inhibit ingestive behaviors and stimulate metabolism, leptin's activational effect on the reproductive axis is likely to be mediated by other, unknown neuroendocrine circuits.


1987 ◽  
Vol 252 (3) ◽  
pp. R599-R609 ◽  
Author(s):  
J. E. Morley ◽  
A. S. Levine ◽  
B. A. Gosnell ◽  
J. Kneip ◽  
M. Grace

Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.


2018 ◽  
Vol 314 (5) ◽  
pp. R734-R740 ◽  
Author(s):  
Ulrika Smedh ◽  
Karen A. Scott ◽  
Timothy H. Moran

Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.


2020 ◽  
Author(s):  
Jianzheng He ◽  
Alice Tan ◽  
Si Ng ◽  
Fengwei Yu

Abstract Cannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster, or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of their sensory functions. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jianzheng He ◽  
Alice Mei Xien Tan ◽  
Si Yun Ng ◽  
Menglong Rui ◽  
Fengwei Yu

AbstractCannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster, or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of two important sensory regulators Poxn and Orco. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.


1990 ◽  
Vol 259 (2) ◽  
pp. R317-R323 ◽  
Author(s):  
E. S. Corp ◽  
L. D. Melville ◽  
D. Greenberg ◽  
J. Gibbs ◽  
G. P. Smith

We studied the effect of fourth intracerebroventricular administration of neuropeptide Y (NPY) and peptide YY (PYY) on ingestive and other behaviors in awake nondeprived rats. Injection of NPY or PYY into the fourth ventricle produced a significant dose-related increase in food intake and reduction in the latency to eat. PYY was more potent than NPY in increasing food intake and decreasing latency to eat, suggesting that PYY-preferring receptors sensitive to the orexigenic effects of NPY and PYY exist in the hindbrain. In addition, both peptides increased water intake when food was present but not when food was absent, suggesting that a neural substrate supporting a direct action of NPY and PYY on water intake is not present in the hindbrain. In time sampling of behaviors occurring during a 90-min feeding test, we found that both peptides increased the time spent eating and reduced grooming. In addition PYY, but not NPY, reduced apparent sleep and increased exploratory activity. This suggests that PYY, but not NPY, influences a hindbrain neural substrate involved in sleep and activity.


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