Source: VIRGINIA POLYTECHNIC INSTITUTE submitted to
REGULATION OF FEED INTAKE IN POULTRY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0195584
Grant No.
(N/A)
Project No.
VA-135699
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Jul 1, 2003
Project End Date
Jun 30, 2008
Grant Year
(N/A)
Project Director
Denbow, D. M.
Recipient Organization
VIRGINIA POLYTECHNIC INSTITUTE
(N/A)
BLACKSBURG,VA 24061
Performing Department
ANIMAL AND POULTRY SCIENCES
Non Technical Summary
Within the poultry industry, there is a need to develop stratgies to both increase and decrease food intake. Currently, the most common method to decrease food intake involves the physical restriction of feed. However, this results in animal welfare issues. The goal of the present project is to further elucidate the mechanisms controlling feed intake. Understanding such mechanisms will allow the development of other methods such as feed supplements which can be used to alter feed intake in poultry
Animal Health Component
25%
Research Effort Categories
Basic
75%
Applied
25%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3023220102025%
3023220104025%
3053220102025%
3053220104025%
Goals / Objectives
Objective 1: To determine if there are polymorphisms in the leptin receptor gene between lines of chickens selected for high (HWS)or low (LWS) body weight. Objective 2: To determine if there are differences in leptin receptor gene expression between HWS and LWS chickens. Objective 3: To determine if polymorphisms exist between the genes coding for CRH and its receptor in these lines of chickens. Objective 4: To determine the effects of ICV injections of putative neurotransmitters on feed intake in chickens.
Project Methods
For objectives 1 and 3, genomic DNA will be isolated from the red blood cells of both the high- and low-weight lines of chickens. Primers will be designed for use in PCR in order to amplify either the leptin receptor, CRH receptor or CRH. The DNA will be amplified using PCR, and the products will be collected and sequenced to determined if polymorphisms exist. For objective 2, RNA will be collected from various organs from both lines of chickens. Real Time PCR will be conducted to determine RNA expression for the leptin receptor in both lines of birds. For objective 4, both lines of birds will be injected intracerebroventricularly with different levels of either leptin or CRH. Food and water intake will be monitored at 15 minute intervals through three hours postinjection.

Progress 07/01/03 to 06/30/08

Outputs
OUTPUTS: The central nervous system plays an important role in the neurochemical control of food intake. To further understand these mechanisms in chickens, during the last year, we investigated the effects of alpha melanocyte stimulating hormone (MSH) on food intake in chickens. Specifically, the effects were investigated in lines of chickens selected for over 50 generations for either high (HWS) or low (LWS) eight-week body weight. Using chicks 5 days-of-age, The intracerebroventricular injection 024, 120 or 600 pmole of MSH dose-dependently decreased food intake in the LWS chickens while only the high dose of MSH decreased food intake in the HWS chickens. Water intake was not affected by MSH in either line. To further understand the mechanism of MSH, the activity of c-Fos was determined in various hypothalmic nuclei. In both lines of chickens, c-Fos immunoreactivity increased in the dorsomedial hypothalamus, paraventricular nucleus, and ventromedial hypothalamus, although the magnitude of increase was musch greater in the LWS than HWS birds. It appears that selection for low eight week body weight has resulted in an increased responsiveness relative to that seen in chickens selected for increased body weight to the anorexigenic agent MSH. During the length of this project, we have shown that selection for growth has altered the neurochemical mechanisms controlling food intake. Results of this project have shown that selection for decreased body weight has increased the responsiveness of the brain to neurochemicals that decrease food intake. The LWS chickens had greater leptin receptor gene expression than HWS chickens. Furthermore, intense selection for increased body weight changed the sequence of the leptin receptor in HWS birds. HWS birds responded with a greater decrease in food intkae than LWS birds when injected with reserpine, a compound that disrupts synaptic vesicles and depletes brain monoamines. Corticotrophin releasing factor (CRF) decreased food intake in both lines; however, the LWS chickens responded to a lower dose than the HWS. Additionally, the CRF receptor antagonist astressin increased feed intake in the LWS, but not HWS, chickens. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Relevance: Through genetic selection, the poultry industry has developed specialized lines of birds for either meat production or egg production. Selction for meat production has resulted in increased appetites while selection for egg production results in decreased appetites. Our studies are designed to better understand the mechanism controlling food intake in poultry, and how selection for either increased or decreased body weight has altered these mechanisms. Results: It appears that divergent selection for body weight has altered the sensitivity to neurochemicals controlling food intake.

Publications

  • Cline, M. A., W. Nandar, P. P. Hein, D. M. Denbow, and P. B. Siegel, 2008. Differential feeding responses to central alpha-melanocyte stimulating hormone in genetically low and high body weight select lines of chicks. Life Sci. 83:208-213.
  • Cline, M. A., A. Y. Kuo, M. L.Smith, P. B. Siegel, and D. M. Denbow, 2008. Differential feed intake responses to central corticotrophin releasing factor in lines of chickens divergently selected for low or high body weight. Comp. Biochem. Physiol. (In Press)


Progress 10/01/06 to 09/30/07

Outputs
In order to help elucidate the neurochemical mechanisms controlling food intake, various neurotransmitters were injected intracerebroventricularly (ICV) into male chickens that were from lines selected for either high (HWS) or low (LWS) eight-week body weight. Obestatin is a peptide that has been shown to inhibit food intake in mammals, having an effect opposite that of ghrelin. Ghrelin, which is secreted from the stomach, is an endogenous ligand for the GHS-1 receptor which is expressed on neurons that synthesize neuropeptide Y (NPY). The ICV injection of obestatin increased food intake in HWS chickens, but caused a decrease in food intake in LWS chickens. Ghrelin induced a decrease and increase in food intake in HWS and LWS chickens, respectively. Therefore, it appears that obestatin and ghrelin have effects on food intake in chickens, but these effects vary from those observed in mammals. NPY is a neurotransmitter known to stimulate food intake when injected ICV in mammals and chickens. Since obestatin and ghrelin may affect NPY neurons in the arcuate nucleus located in the hypothalamus, studies have begun to verify the roll of NPY on food intake in HWS and LWS chickens. The ICV injection of NPY stimulated food intake in LWS chickens. It remains to be determined what effect NPY has in HWS chickens. Finally, visfatin is a recently discovered peptide isolated from the visceral fat of humans and mice called visfatin. It has been reported that plasma visfatin concentrations are increased in overweight and obese humans with metabolic syndrome. However, the effect of visfatin on food intake has not been determined in any species. Thus, we investigated the effect of visfatin on food intake in broiler-type chickens. The ICV injection of visfatin increased food intake in voung broiler chicks, and increased activity of the lateral hypothalamic area. It appears, therefore, that visfatin is an oerexigenic peptide in chickens.

Impacts
Relevance: Broiler-type chickens have been genetically selected over several decades for rapid growth rate. The genetic gains seen in body weight have been largely due to increases in food intake. However, the physiological mechanisms by which food intake have increased are not well understood. Response: The current studies are designed to further enhance our understanding of mechanisms controlling food intake. Results: The results of these studies show that the neurochemical mechanisms controlling food in chickens differ from those in mammals, and that selection for eight-week body weight has further changed these mechanisms. Finally, it was also shown that visfatin can stimulate food intake in chickens, thus making it one of the few neurotransmitters acting in the brain to increase food intake. These results will help target possible pharmacological approaches to altering food intake in poultry.

Publications

  • Yang, S. J., and D. M. Denbow, 2007. Interaction of leptin and nitric oxide on food intake in broilers and Leghorns. Physiol. Behav. 92:651-657.
  • 180.Cline, M. A., W. Nandar, B. C. Prall, C. N. Bowden, and D. M. Denbow, 2007. Central visfatin causes orexigenic effects in chicks. Behavioural Brain Research 186:293-297.
  • Yamane, H., S. Tomonaga, R. Suenaga, D. M. Denbow, M.Furuse, 2007. Intracerebroventricular injection of glutathione suppresses food intake of neonatal chicks. Journal of Animal and Veterinary Advances 6:1247-1249.
  • Haraguchi, T., S. Tomonaga, I. Kurauchi, K. Hamasu, D. M. Denbow and M. Furuse, 2007. Intracerebroventricular injection of L-proline modifies food intake in neonatal chicks. Journal of Animal and Veterinary Advances 6:1255-1257.


Progress 10/01/05 to 09/30/06

Outputs
Sphingomyelin (SM) is a lipid found in high concentrations in the myelin sheaths of neurons. In addition to being found in the myelin sheath, SM is also a bioactive compound affecting carcinogenesis and lipid secretion from the liver. To determine if this compound is involved in the central nervous system control of food intake, it was injected intracerebroventricularly (ICV) into 6-day old chicks. The ICV injection of SM decreased food intake in fasted chicks. To determine the possible mechanism of action of SM, its affect on the hypothalamopituitary axis was determined, as well as its affect on diencephalic serotonin (5-HT) levels. SM had no affect on plasma corticosterone or glucose levels. Similarly, SM had no affect on diencephalic 5-HT levels. Therefore, SM appears to act in the brain to affect food intake, but its mechanism of action is unclear. Ghrelin is a peptide hormone secreted from the stomach and has been shown to increase food intake in mammals. However, in chickens, ICV injection of ghrelin decreases food intake. To further investigate the role of ghrelin on intake, its afffect on water intake was determined. The ICV injection of ghrelin inhibited water intake in 4-day old chicks. Since brain atrial natriuretic peptide (BNP) has previous been shown in rats to have antidipsogenic effects, the effect of ghrelin on water intake was compared to BNP. The ICV injection of BNP did not have a similar affect, suggesting that ghrelin was not working through BNP. It appears that ghrelin can work within the central nervous system to affect water intake, possibly by working at the growth hormone secretagogue receptor.

Impacts
Relevance: Over the last several decades, the improvement in growth and performance of broiler chickens has come largely through an increase in food intake. In order to continue making progress in growth of chickens, it is necessary to further understand the mechanisms controlling food intake in chickens. Response: The present study was designed to help further understand the mechanisms in the brain that help control food and water intake in poultry. Results: The results show that a lipid, sphingomyelin, acts in the brain to decrease food intake. In addition, ghrelin, a peptide that appears to have an opposite effect on food intake in birds and mammals, decreases water intake when injected into the brain of chickens. Results of these experiments help further our understanding of the brain mechanisms controlling both food and water intake in chickens. These results will help in developing strategies to both increase and decrease food intake in poultry.

Publications

  • Emoto, F., S. Tomonaga, T. Tachnibana, D. M. Denbow, and M. Furuse, 2006. Effect of centrally administered sphingomyelin on food intake and HPA axis in chicks. Journal of Applied Animal Research 29:91-96
  • Tachibana, T., H. Kaiya, D. M. Denbow, K. Kangawaa, and M. Furuse, 2006. Central ghrelin acts as an anti-dipsogenic peptide in chicks. Neuroscience Letters 405:241-245.
  • Kuo, A. Y., J. C. Lee, G. Magnin, P. B. Siegel, and D. M. Denbow, 2006. Differential autonomic nervous system response in obese and anorexic chickens (Gallus gallus). Comparative Biochemistry and Physiology, Part B 144:359-364.


Progress 10/01/04 to 09/30/05

Outputs
Previous results in our laboratory suggested that selecting lines of chickens for differences in body weight resulted in changes in the balance of the autonomic nervous system. This was verified pharmacologically by showing that lines of chickens divergently selected for high (HWS) and low (LWS) body weight for over 45 generations responded differently to intraperitoneal injections of reserpine, a compound that depletes catecholamines and indoleamines. To further determine is genetic selection for growth has resulted in alterations in the neurochemical mechanisms controlling food intake, we invested the effects of intracerebroventricular (ICV) injection of corticotrophin releasing hormone (CRH) and urocortin, a CRH type 2 receptor agonist, on feed and water intake in these lines of chickens. CRH is normally released as a hormone in response to stress, but it also appears to act within the central nervous system as a neurotransmitter. The ICV injection of either CRH or urocortin decreased feed intake in a dose-dependently manner in 3-hr fasted chicks. The suppression of food intake following both peptides was greatest in the LWS chicks. These results support the hypothesis that the CRH type 2 receptor is involved in controlling food intake in chickens. Water intake was not affected by treatment in either line. Furthermore, these results showed that selection for body weight has altered the neurochemical mechanisms within the central nervous system controlling food intake. The LWS chicks, which previous studies have suggested has a greater sympathetic nervous system tone, appears more sensitive to CRH.

Impacts
Long-term selection for differences in body weight has resulted in significant changes in neurochemical coding within the central nervous system controlling food intake. Selecting for high body weight, and therefore a faster growth rate, has resulted in a greater parasympathetic tone. The parasympathetic nervous system is generally associated with resting and relaxing, resulting in less expenditure of energy while simultaneously

Publications

  • Saito, E-S., H. Kaiya, T. Tachibana, S. Tomonaga, D. M. Denbow, K. Kangawa, and M. Furuse, 2005. Inhibitory effect of ghrelin on food intake is mediated by the corticotropin-releasing factor system in neonatal chicks. Regulatory Peptide 125:201-208.
  • Koga, Y., H. Takahashi, D. Oikawa, T. Tachibana, T., D. M. Denbow, D.M., and M. Furuse, 2005. Brain creatine functions to attenuate stress responses through GABAnergic system in chicks. Neuroscience 132:65-71.
  • Kuo, A. Y., M. A. Cline, E. Werner, P. B. Siegel,and D. M. Denbow, 2005. Effect of human recombinant leptin on food and water intake in chickens selected for high and low body weight. Physiol. Behav. 84:459-464.
  • Tomonaga, S., T. Tachibama, H. Takahash, M. Sato, D. M. Denbow, and M. Furuse, 2005. Nitric oxide involved in carnosine indued hyperactivity in chicks. Eur. J. Pharmacol. 524:84-88.
  • Takahashi, H., K. Ando, T. Tachibana, D. M. Denbow and M. Furuse, 2005. Regulation of body temperature by thyrotropin releasing hormone in neonatal chicks. Developmental Brain Research 157:58-64.
  • Tomonaga, S., Y. Kaji, T. Tachibana, D. M. Denbow, and M. Furuse, 2004. Oral administration of -alanine modifies carnosine contents of the muscle and brain in chicks. Anim. Sci. J. 76:249-254.
  • Koutoku, T., H. Takahashi, S. Tomonaga, D. Oikawa, S. Saito, T. Tachibana, L. Han, L., K. Hayamizu, K., D. M. Denbow, and M. Furuse, 2005. Central administration of phosphatidylserine attenuates isolation stress induced behavior in chicks. Neurochem. Intern. 47:183-189.
  • Saito, S., E-Suke Saito, T. Tachibana, D. M. Denbow, and Mitsuhiro Furuse, 2005. ICV CRF and isolation differentially enhance plasma corticosterone concentrations in layer- and meat-type neonatal chicks. Comp. Biochem. Physiol. Part A 141:305-309.
  • Saito S., T. Tachibana, Y-H. Choi, D. M. Denbow, M. Furuse, 2005. ICV melatonin reduces acute stress responses in neonatal chicks. Behav. Brain Res. 165(2):197-203).
  • Takagi, T, Y-H. Choi, T. Tachibana, D. M. Denbow, and M. Furuse, 2005. Effect of intracerebroventricular injection of L-pipecolic acid on GABA concentrations in brain sites of neonatal chicks. J. Appl. Anim. Res. 28(1):9-13.


Progress 10/01/03 to 09/30/04

Outputs
Lines of chickens that have been divergently selected for high (HWS) and low (LWS) body weight for over 45 generations were utilized to determine how genetic selection altered food intake control mechanisms. These lines of birds responded differently to intraperitoneal injections of reserpine. While reserpine caused a transitory decrease in food intake and body weight in both lines, the magnitude of the change was greater in the HWS than in the LWS chickens. However, chickens from the LWS line exhibited greater catecholamine and indoleamine level changes in response to reserpine than those from the HWS line. In the LWS birds, norepinephrine concentration decreased in a quadratic manner in response to the various doses of reserpine, but not in the HWS birds. The epinephrine concentration decreased in a linear and quadratic manner in LWS, but not HWS line. There were also differences in the leptin receptor gene expression between HWS and LWS lines of chickens in various organs and ages. Leptin receptor expression in the whole brain was significantly different between sexes at 28 days-of-age in the HWS and LWS lines. The LWS line had higher leptin receptor gene expression in the liver at 2 days-of-age than at 56 and 363 days-of-age, but no differences were observed in the HWS line. In addition, at 2 days-of age, liver leptin receptor gene expression was higher in LWS than HWS chickens, but the reverse was observed at 363 days-of age. In adipose tissue, leptin receptor expression was higher in the LWS than HWS line. Leptin receptor expression in adipose tissue was greater at 363, than 28 and 56 days-of-ages.

Impacts
Genetic selection for growth in chickens has altered the central nervous system control mechanisms for food intake regulation. Recent studies show that differences in food intake between the lines is partially the result of alterations in leptin signaling. The low weight select lines of birds were more sensitive to the injection of leptin directly into the brain than the lines of birds selected for high body weight. Interestingly, the LWS birds had higher plasma levels of leptin that correlate with lower food intake. Furthermore, intense genetic selection for body with has also altered the gene sequence for the leptin receptor. Furthermore, these results have implications in the etiology of obesity in humans since the HWS line of birds is relatively obese compared to the LWS line.

Publications

  • Yamasaki, I., K. Sashihara, T. Takagi, T. Nakanishi, D. M. Denbow, and M. Furuse, 2003. Comparison of hypothalamic monoamines of broiler- and layer-type chickens at prehatch and posthatch. J. Poultry Sci. 40:282-289.
  • Jonaidi, H., M.M. Oloumi, and D. M. Denbow, 2003. Behavioral effects of intracerebroventricular injection of oxytocin in birds. Physiol. Behav. 79:725-729.
  • Zhang, R., T. Tachibana, T. Takagi, T. Koutoku, D. M. Denbow, and M. Furuse, 2003. Central administered norepinephrine modifies the behavior induced by corticotropin-releasing factor in neonatal chicks. J. Neurosci. Res. 74:630-636.
  • Zhang, R., T. Tachibana, T. Takaki, T. Koutoku, D. M. Denbow, and M. Furuse, 2004. Serotonin modified the corticotropin-releasing factor induced behaviors of chicks. Behavioural Brain Res. 151:47-52.
  • Tachibana, T. Ei-S. Saito, S. Saito, S. Tomonaga, D. M. Denbow, M. Furuse, 2004. Comparison of brain arginine-vasotocin and corticotrophin-releasing factor for physiological responses in chicks. Neuroscience Lett. 360:165-169.
  • Saito S, T. Takagi, T. Koutoku, E-s. Saito, H. Hirakawa, S. Tomonaga, T. Tachibana, D. M. Denbow and M. Furuse, 2004. Differences in catecholamine metabolism and behaviour in neonatal broiler and layer chicks. Brit. Poultry Sci. 45:158-162.
  • Tomonaga S, T. Tachibana, T. Takagi, E-S. Saito, R. Zhang R, D. M. Denbow, and M. Furuse, 2004. Effect of central administration of carnosine and its constituents on behaviors in chicks. Brain Res. Bull. 63: 75-82.


Progress 10/01/02 to 09/30/03

Outputs
Using lines of chickens that have been divergently selected for high (HWS) and low (LWS) body weight for over 45 generations, experiments were conducted to determine if these lines of birds respond differently to intracerebroventricular ICV injections of human leptin. Food intake decreased in a dose-dependent manner following the ICV injection of leptin in LWS birds. However, in the HWS birds, the ICV injection of leptin had no affect on food intake. When measuring the plasma levels of leptin, it was found that LWS birds had higher levels than HWS. Furthermore, there was a line by sex interaction for plasma leptin concentrations. The HWS females had significantly lower leptin concentrations than the HWS male of LWS females. Finally, studies were completed to determine if there were polymorphisms in the leptin receptor between the lines. There was a single nucleotide polymorphism between the HWS and LWS lines. There was a single polymorphism at nucleotide 182 within the intron in which C was replaced by T compared to previously reported sequences in chickens. The T-type allele was present in the LWS line in both the homozygous (T-T) and heterozygous (T-C) form. The HWS has only the homozygous (T-T) form.

Impacts
Genetic selection for growth in chickens has altered the central nervous system control mechanisms for food intake regulation. Recent studies show that differences in food intake between the lines is partially the result of alterations in leptin signaling. The low weight select lines of birds were more sensitive to the injection of leptin directly into the brain than the lines of birds selected for high body weight. Interestingly, the LWS birds had higher plasma levels of leptin that correlate with lower food intake. Furthermore, intense genetic selection for body with has also altered the gene sequence for the leptin receptor. Furthermore, these results have implications in the etiology of obesity in humans since the HWS line of birds is relatively obese compared to the LWS line.

Publications

  • Tachibana, T., T. Takagi, S. Tomonaga, A. Ohgushi, R. Ando, D. M. Denbow, and M. Furuse, 2003. Central administration of cocaine- and amphetamine-regulated transcript inhibits food intake in chicks. Neurosci. Letters 337:131-134.
  • Takagia, T, R. Andoa, A. Ohgushia, T. Nakanishia, H. Hussain-Yusuf, R. Onoderab, H. Satoc, D. M. Denbow, M. Furuse, 2003. Effect of oral administration of L-pipecolic acid on food intake in chicks and mice. Animal Science Journal (in press).
  • Saito, S., T. Takagi, T. Koutoku, D. M. Denbow, and M. Furuse, 2003. Feeding condition and strain difference influence sleeping behavior in newborn chicks. J. Poult. Sci. 40:62-68.
  • Meade, S. and D. Michael Denbow, 2003. The interaction of bombesin and corticotropin-releasing hormone on ingestive behavior in the domestic fowl. Physiol. Behav. 78:611-614
  • Takagi, T., T. Bungo, T. Tachibana, E.-s. Saito, S. Saito, I. Yamasaki, S.Tomonaga, D. M. Denbow, and M. Furuse, 2003. Intracerebroventriuclar administration of GABA-A and GABA-B receptor antagonists attenuate feeding and sleep-like behavior induced by L-pipecolic acid in neonatal chick. J. Neurosci. Res. 73:270-275.
  • Tachibana, T., T. Takagi, E.-S. Saito, S. Tomonaga, R. Zhang, Y. Koga, Y. Kido, D. M. Denbow, M. Furuse, 2003. Central administration of a beta 3 adrenergic receptor agonist inhibits food intake of chicks. Comparative Biochemistry and Physiology A, Molecular and Integrative Physiology (in press).
  • Takagia, T., T. Tachibanaa, E-S. Saitoa, S. Tomonagaa, S. Saitoa, T. Bungob, D. M. Denbow, and M. Furuse, 2003. Central pipecolic acid increases food intake under ad libitum feeding conditions in the neonatal chick. Neurosci. Lett. 347:93-96.