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Gregory S Fraley - One of the best experts on this subject based on the ideXlab platform.
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icv Galanin Like Peptide stimulates non contact erections but not touch based erections in adult sexually experienced male rats
Neuropeptides, 2017Co-Authors: Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) is a neuroPeptide transcribed only within the arcuate nucleus of the hypothalamus and is thought to be a mediator between energetics and reproductive function. Intracerebroventricular (ICV) injection of GALP is known to have effects on feeding, and to significantly increase gonadotropin releasing hormone- (GnRH-) mediated luteinizing hormone (LH) secretion. Furthermore, ICV GALP is known to stimulate fos production in the medial pre-optic area (mPOA) and to a lesser extent, the paraventricular nucleus (PVN). ICV injection of 5.0nmol GALP profoundly stimulates male rat sexual behavior. It is not known if GALP's effects on sex behavior are due to an increase in appetitive or mechanical (erectile) aspects of male sexual behavior. To determine this, sexually experienced male rats were cannulated in the lateral ventricle and injected with 5.0nmol GALP or vehicle. Immediately after injections, male rats were placed in an arena connected to a second arena via a tube with a fan. The second arena contained a steroid-primed female and her bedding. The male rat had olfactory but not visual or tactile contact with the female. We analyzed the amount of time the male rats spent investigating the air intake and the number of non-contact erections (NCEs) in a 30minute test. ICV GALP significantly (p<0.05) increased both the amount of time of olfactory investigations and NCEs compared to vehicle. In a second set of animals, we tested if ICV GALP could stimulate touch-based erections. GALP had no significant effect on touch-based erections compared to vehicle. These data suggest that GALP's activation of fos within the mPOA is indicative of its action to stimulate the appetitive aspects of male sexual behavior.
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ICV Galanin-Like Peptide stimulates non-contact erections but not touch-based erections in adult, sexually experienced male rats
Neuropeptides, 2017Co-Authors: Gregory S FraleyAbstract:Abstract Galanin-Like Peptide (GALP) is a neuroPeptide transcribed only within the arcuate nucleus of the hypothalamus and is thought to be a mediator between energetics and reproductive function. Intracerebroventricular (ICV) injection of GALP is known to have effects on feeding, and to significantly increase gonadotropin releasing hormone- (GnRH-) mediated luteinizing hormone (LH) secretion. Furthermore, ICV GALP is known to stimulate fos production in the medial pre-optic area (mPOA) and to a lesser extent, the paraventricular nucleus (PVN). ICV injection of 5.0 nmol GALP profoundly stimulates male rat sexual behavior. It is not known if GALP's effects on sex behavior are due to an increase in appetitive or mechanical (erectile) aspects of male sexual behavior. To determine this, sexually experienced male rats were cannulated in the lateral ventricle and injected with 5.0 nmol GALP or vehicle. Immediately after injections, male rats were placed in an arena connected to a second arena via a tube with a fan. The second arena contained a steroid-primed female and her bedding. The male rat had olfactory but not visual or tactile contact with the female. We analyzed the amount of time the male rats spent investigating the air intake and the number of non-contact erections (NCEs) in a 30 minute test. ICV GALP significantly (p
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hypothalamic Galanin Like Peptide rescues the onset of puberty in food restricted weanling rats
Journal of Neuroendocrinology, 2012Co-Authors: Margaret A. Mohr, Emily Leathley, Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) is a known mediator of metabolism and reproduction; however, the role that GALP plays in the onset of puberty is unknown. First, we tested the hypothesis that central GALP administration could rescue puberty in food-restricted weanling rats. GALP treatment in food-restricted rats of both sexes rescued the timing of the onset of puberty to that seen in ad lib. fed controls. Second, we tested whether GALP translation knocked-down in ad lib. fed, prepubertal rats would alter the timing of puberty. Knock-down females, but not males, showed a significant (P < 0.01) delay in the onset of puberty compared to controls. Third, we sought evidence that the role of GALP in pubertal onset is mediated by the kisspeptin system. In situ hybridisation analyses showed a significant (P < 0.01) reduction in Kiss1 mRNA within the hypothalamic arcuate nucleus in food-restricted rats compared to ad lib. fed controls and this reduction was prevented with i.c.v. GALP administration. Furthermore, analyses of Fos-immunoreactivity (-IR) after i.c.v. GALP treatment did not elicit Fos-IR within any kisspeptin neurones, nor are GALP and kisspeptin Peptides or mRNA colocalised. These data demonstrate that hypothalamic GALP infusion maintained the onset of puberty in food-restricted weanling rats, although probably not via direct innervation of kisspeptin neurones.
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Hypothalamic Galanin‐Like Peptide Rescues the Onset of Puberty in Food‐Restricted Weanling Rats
Journal of neuroendocrinology, 2012Co-Authors: Margaret A. Mohr, Emily Leathley, Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) is a known mediator of metabolism and reproduction; however, the role that GALP plays in the onset of puberty is unknown. First, we tested the hypothesis that central GALP administration could rescue puberty in food-restricted weanling rats. GALP treatment in food-restricted rats of both sexes rescued the timing of the onset of puberty to that seen in ad lib. fed controls. Second, we tested whether GALP translation knocked-down in ad lib. fed, prepubertal rats would alter the timing of puberty. Knock-down females, but not males, showed a significant (P < 0.01) delay in the onset of puberty compared to controls. Third, we sought evidence that the role of GALP in pubertal onset is mediated by the kisspeptin system. In situ hybridisation analyses showed a significant (P < 0.01) reduction in Kiss1 mRNA within the hypothalamic arcuate nucleus in food-restricted rats compared to ad lib. fed controls and this reduction was prevented with i.c.v. GALP administration. Furthermore, analyses of Fos-immunoreactivity (-IR) after i.c.v. GALP treatment did not elicit Fos-IR within any kisspeptin neurones, nor are GALP and kisspeptin Peptides or mRNA colocalised. These data demonstrate that hypothalamic GALP infusion maintained the onset of puberty in food-restricted weanling rats, although probably not via direct innervation of kisspeptin neurones.
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Galanin-Like Peptide: Neural regulator of energy homeostasis and reproduction
Experientia supplementum (2012), 2010Co-Authors: Catherine B. Lawrence, Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) was discovered in 1999 in the porcine hypothalamus and was found to be a 60 amino-acid neuroPeptide. GALP shares sequence homology to Galanin (1–13) in position 9–21 and can bind to and activate the three Galanin receptor subtypes (GalR1–3). GALP-expressing cells are limited, and are mainly found in the arcuate nucleus of the hypothalamus (ARC) and the posterior pituitary. GALP-positive neurons in the ARC, project to several brain regions where they appear to make contact with several neuromodulators that are involved in the regulation of energy homeostasis and reproduction, anatomical evidence that suggests a role for GALP in these physiological functions. In support of this idea, GALP gene expression is regulated by several factors that reflect metabolic state including the metabolic hormones leptin and insulin, thyroid hormones, and blood glucose. Considerable evidence now exists to support the hypothesis that GALP has a role in the regulation of energy homeostasis and reproduction; and, that that GALP’s role may be independent of the known Galanin receptors. In this chapter we (1) provide an overview of the distribution of GALP, and discuss the potential relationship between GALP and other neuromodulators of energy homeostasis and reproduction, (2) discuss the metabolic factors that regulate GALP expression, (3) review the evidence for the role of GALP in energy homeostasis and reproduction, (4) discuss the potential downstream mediators and mechanisms underlying GALP’s effects, and (5) discuss the possibility that GALP may mediate it’s effects via an as yet unidentified GALP-specific receptor.
Robert A. Steiner - One of the best experts on this subject based on the ideXlab platform.
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Effects of Diabetes and Insulin on the Expression of Galanin-Like Peptide in the Hypothalamus of the Rat
2016Co-Authors: Donald K. Clifton, Robert A. SteinerAbstract:Galanin-Like Peptide (GALP) is produced in a small population of neurons in the arcuate nucleus of the hypothalamus, and leptin stimulates the hypothalamic expression of GALP mRNA. Because insulin and leptin share common signaling pathways in the brain, we rea-soned that GALP neurons might also be responsive to changes in circulating concentrations of insulin. To test this hypothesis, we first studied the effect of insulin deficiency on the expression of GALP by comparing levels of GALP mRNA between normal and diabetic animals. Streptozotocin-induced diabetes was associ-ated with a significant reduction in the expression of GALP mRNA, which was reversed by treatment with either insulin or leptin. Second, we examined the effect of insulin administered directly into the brain on th
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Galanin-Like Peptide as a Possible Link between Metabolism and Reproduction in the Macaque
2015Co-Authors: Matthew J Cunningham, Tony M Plant, Donald K. Clifton, Muhammad Shahab, Jarrad M Scarlett, Kevin L. Grove, Judy L. Cameron, Susan M. Smith, Robert A. SteinerAbstract:Galanin-Like Peptide (GALP) is a hypothalamic neuroPeptide that has been implicated in the control of feeding, metabolism, and reproduction. The goal of this study was to examine the effects of central infusions of GALP on GnRH and LH secre-tion and to identify physiological factors that influence the expression of GALP mRNA in the brain of a primate species. Infusions of GALP into the lateral cerebroventricle of the macaque caused a significant increase in LH secretion, which was blocked by administration of the GnRH receptor antag-onist acyline. However, the expression of GALP mRNA in the arcuate nucleus, as determined by in situ hybridization, was not regulated by either estradiol or progesterone. Compared with feeding ad libitum, fasting for 48 h produced a significant reduction in the hypothalamic expression of GALP mRNA. GALP neurons were found to express both neuroPeptide Y Y
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Altered response to metabolic challenges in mice with genetically targeted deletions of Galanin-Like Peptide
American Journal of Physiology-endocrinology and Metabolism, 2008Co-Authors: Heather M. Dungan Lemko, Donald K. Clifton, Robert A. Steiner, Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) is expressed in the arcuate nucleus and is implicated in the neuroendocrine regulation of metabolism and reproduction. To investigate the physiological significance of GALP, we generated and characterized a strain of mice with a genetically targeted deletion in the GALP gene [GALP knockout (KO) mice]. We report that GALP KO mice have a subtle, but notable, metabolic phenotype that becomes apparent during adaptation to changes in nutrition. GALP KO mice are indistinguishable from wild-type (WT) controls in virtually all aspects of growth, sexual development, body weight, food and water consumption, and motor behaviors, when they are allowed unlimited access to standard rodent chow. However, GALP KO mice have an altered response to changes in diet. 1) Male GALP KO mice consumed less food during refeeding after a fast than WT controls (P < 0.01). 2) GALP KO mice of both sexes gained less weight on a high-fat diet than WT controls (P < 0.01), despite both genotypes having consumed equal amounts of food. We conclude that although GALP signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, GALP may play a role in readjusting energy balance under changing nutritional circumstances.
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Effects of Galanin-Like Peptide on luteinizing hormone secretion in the rat: sexually dimorphic responses and enhanced sensitivity at male puberty
American Journal of Physiology-endocrinology and Metabolism, 2006Co-Authors: Juan M Castellano, Rosario Fernandez-fernandez, E Vigo, Rafael Pineda, Robert A. Steiner, Leonor Pinilla, Victor Navarro, Enrique Aguilar, Manuel Tena-sempereAbstract:Reproductive function is exquisitely sensitive to adequacy of nutrition and fuel reserves, through mechanisms that are yet to be completely elucidated. Galanin-Like Peptide (GALP) has recently emer...
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Effects of Galanin-Like Peptide on luteinizing hormone secretion in the rat: sexually dimorphic responses and enhanced sensitivity at male puberty
American journal of physiology. Endocrinology and metabolism, 2006Co-Authors: Juan M Castellano, Rosario Fernandez-fernandez, E Vigo, Rafael Pineda, Robert A. Steiner, Leonor Pinilla, Enrique Aguilar, Víctor M. Navarro, Juan Carlos Roa, Manuel Tena-sempereAbstract:Reproductive function is exquisitely sensitive to adequacy of nutrition and fuel reserves, through mechanisms that are yet to be completely elucidated. Galanin-Like Peptide (GALP) has recently emerged as another neuroPeptide link that couples reproduction and metabolism. However, although the effects of GALP on luteinizing hormone (LH) secretion have been studied, no systematic investigation on how these responses might differ along sexual maturation and between sexes has been reported. Moreover, the influence of metabolic status and potential interplay with other relevant neurotransmitters controlling LH secretion remain ill defined. These facets of GALP physiology were addressed herein. Intracerebral injection of GALP to male rats induced a dose-dependent increase in serum LH levels, the magnitude of which was significantly greater in pubertal than in adult males. In contrast, negligible LH responses to GALP were detected in pubertal or adult female rats at diestrus. Neonatal androgen treatment to females failed to "masculinize" the pattern of LH response to GALP. In addition, metabolic stress by short-term fasting did not prevent but rather amplified LH responses to GALP in pubertal males, whereas these responses were abrogated by pharmacological inhibition of nitric oxide synthesis. We conclude that the ability of GALP to evoke LH secretion is sexually differentiated, with maximal responses at male puberty, a phenomenon which was not reverted by manipulation of sex steroid milieu during the critical neonatal period and was sensitive to metabolic stress. This state of LH hyperresponsiveness may prove relevant for the mechanisms relaying metabolic status to the reproductive axis in male puberty.
Donald K. Clifton - One of the best experts on this subject based on the ideXlab platform.
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Effects of Diabetes and Insulin on the Expression of Galanin-Like Peptide in the Hypothalamus of the Rat
2016Co-Authors: Donald K. Clifton, Robert A. SteinerAbstract:Galanin-Like Peptide (GALP) is produced in a small population of neurons in the arcuate nucleus of the hypothalamus, and leptin stimulates the hypothalamic expression of GALP mRNA. Because insulin and leptin share common signaling pathways in the brain, we rea-soned that GALP neurons might also be responsive to changes in circulating concentrations of insulin. To test this hypothesis, we first studied the effect of insulin deficiency on the expression of GALP by comparing levels of GALP mRNA between normal and diabetic animals. Streptozotocin-induced diabetes was associ-ated with a significant reduction in the expression of GALP mRNA, which was reversed by treatment with either insulin or leptin. Second, we examined the effect of insulin administered directly into the brain on th
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Galanin-Like Peptide as a Possible Link between Metabolism and Reproduction in the Macaque
2015Co-Authors: Matthew J Cunningham, Tony M Plant, Donald K. Clifton, Muhammad Shahab, Jarrad M Scarlett, Kevin L. Grove, Judy L. Cameron, Susan M. Smith, Robert A. SteinerAbstract:Galanin-Like Peptide (GALP) is a hypothalamic neuroPeptide that has been implicated in the control of feeding, metabolism, and reproduction. The goal of this study was to examine the effects of central infusions of GALP on GnRH and LH secre-tion and to identify physiological factors that influence the expression of GALP mRNA in the brain of a primate species. Infusions of GALP into the lateral cerebroventricle of the macaque caused a significant increase in LH secretion, which was blocked by administration of the GnRH receptor antag-onist acyline. However, the expression of GALP mRNA in the arcuate nucleus, as determined by in situ hybridization, was not regulated by either estradiol or progesterone. Compared with feeding ad libitum, fasting for 48 h produced a significant reduction in the hypothalamic expression of GALP mRNA. GALP neurons were found to express both neuroPeptide Y Y
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Altered response to metabolic challenges in mice with genetically targeted deletions of Galanin-Like Peptide
American Journal of Physiology-endocrinology and Metabolism, 2008Co-Authors: Heather M. Dungan Lemko, Donald K. Clifton, Robert A. Steiner, Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) is expressed in the arcuate nucleus and is implicated in the neuroendocrine regulation of metabolism and reproduction. To investigate the physiological significance of GALP, we generated and characterized a strain of mice with a genetically targeted deletion in the GALP gene [GALP knockout (KO) mice]. We report that GALP KO mice have a subtle, but notable, metabolic phenotype that becomes apparent during adaptation to changes in nutrition. GALP KO mice are indistinguishable from wild-type (WT) controls in virtually all aspects of growth, sexual development, body weight, food and water consumption, and motor behaviors, when they are allowed unlimited access to standard rodent chow. However, GALP KO mice have an altered response to changes in diet. 1) Male GALP KO mice consumed less food during refeeding after a fast than WT controls (P < 0.01). 2) GALP KO mice of both sexes gained less weight on a high-fat diet than WT controls (P < 0.01), despite both genotypes having consumed equal amounts of food. We conclude that although GALP signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, GALP may play a role in readjusting energy balance under changing nutritional circumstances.
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Galanin-Like Peptide Rescues Reproductive Function in the Diabetic Rat
Diabetes, 2005Co-Authors: Angela G. Stoyanovitch, Marlie A. Johnson, Donald K. Clifton, Robert A. Steiner, Gregory S FraleyAbstract:Galanin-Like Peptide (GALP) is expressed in the hypothalamic arcuate nucleus and is regulated by leptin and insulin. Centrally administered GALP stimulates gonadotropin secretion and sexual behavior in the rat. Type 1 diabetes is associated with reduced expression of GALP, as well as an overall decline in reproductive function. We postulated that tonic activity of GALP in the brain is required to sustain normal reproductive activity. To test this hypothesis, we examined whether central (intracerebroventricular) immunoblockade of GALP would reduce sexual behaviors and serum levels of luteinizing hormone (LH) in normal adult male rats. We found that GALP antibody reversibly reduced serum levels of LH and abolished male sexual behaviors ( P < 0.05 and 0.001, respectively). Second, we tested whether intracerebroventricular GALP could restore normal plasma LH levels and sexual behavior in diabetic animals. We compared groups of diabetic rats that received intracerebroventricular GALP or vehicle and found that GALP increased serum levels of LH and sexual behavior. Third, we examined whether intracerebroventricular administration of affinity-purified GALP antibody could block the effect of insulin and leptin in reversing the effects of diabetes on LH and sexual behavior. We found that treatment of diabetic animals with insulin and leptin nearly normalized LH levels and sexual behaviors; however, this effect was attenuated by intracerebroventricular administration of GALP antibody ( P < 0.05). These observations demonstrate that endogenous GALP provides trophic support to the neuroendocrine reproductive axis, including sexual behavior.
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Stimulation of sexual behavior in the male rat by Galanin-Like Peptide.
Hormones and Behavior, 2004Co-Authors: Gregory S Fraley, S.e. Thomas-smith, Blake V Acohido, Robert A. Steiner, Donald K. CliftonAbstract:Abstract Galanin-Like Peptide (GALP) is a recently described neuroPeptide, which shares a partial sequence identity with Galanin but is derived from a separate gene. Central injections of GALP stimulate the secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) and induce the expression of Fos in several brain areas known to regulate male sexual behavior in the rat. We postulated that GALP may also stimulate sexual behavior in concert with its stimulatory effect on the hypothalamic–pituitary–gonadal (HPG) axis. To test this hypothesis, we administered GALP, Galanin, or the vehicle (artificial cerebrospinal fluid, aCSF) alone to sexually experienced male rats and assessed the effects of these agents on sexual behavior. We observed that compared to aCSF alone, GALP significantly increased all aspects of male-typical sexual behavior, whereas Galanin inhibited all of these same behaviors. To examine whether the stimulatory effects of GALP on sexual behavior were mediated by GALP's stimulatory effects on the HPG axis, we castrated the same male rats and repeated the behavioral experiment. We found that GALP maintained its inductive action on male-typical sexual behaviors in the castrated animals, suggesting that the effects of GALP on sexual behavior are not the result of GALP's ability to stimulate testosterone secretion. These observations suggest that GALP neurons are part of the hypothalamic circuitry controlling sexual behavior in the male rat.
Seiji Shioda - One of the best experts on this subject based on the ideXlab platform.
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Regulation of Feeding Behavior and Energy Metabolism by Galanin-Like Peptide (GALP): A Novel Strategy to Fight Against Obesity
Current Pharmaceutical Design, 2019Co-Authors: Fumiko Takenoya, Nobuhiro Wada, Haruaki Kageyama, Takahiro Hirabayashi, Satoshi Hirako, Naoko Nonaka, Seiji ShiodaAbstract:Galanin-Like Peptide (GALP) is composed of 60 amino acid residues and its sequence is highly homologous across species. GALP is produced in the hypothalamic arcuate nucleus and has diverse physiological effects such as the regulation of feeding, energy metabolism, and reproductive behavior. GALP-containing neurons express leptin receptors and these neurons form networks in the hypothalamus that contain various Peptides that regulate feeding behavior. Recent studies have revealed that GALP has a central anti-obesity action in addition to its role in food intake regulation. Furthermore, we have found that the respiratory quotient declines shortly after administration of GALP into the lateral ventricle. This suggests that lipid metabolism is accelerated by GALP administration, and identifies a new physiological action for this Peptide. In this review article, we summarize our recent research focusing on the mechanism whereby GALP regulates feeding and energy metabolism. We concentrate on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system and outline the effectiveness of the nasal administration of GALP and basic research towards its clinical application.
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Effect of Intranasal Administration of Galanin-Like Peptide (GALP) on Body Weight and Hepatic Lipids Accumulation in Mice with Diet-induced Obesity
Current Pharmaceutical Design, 2017Co-Authors: Satoshi Hirako, Fumiko Takenoya, Nobuhiro Wada, Mai Okabe, Haruaki Kageyama, Yuzuru Iizuka, Akiyo Matsumoto, Seiji ShiodaAbstract:Galanin-Like Peptide (GALP) is a neuroPeptide involved in the regulation of food intake behavior, body weight and energy metabolism. In previous studies, we demonstrated that the intranasal administration of GALP has weight loss effects, although the mechanism of this action was not clarified. The aim of this study was to demonstrate the functional significance of GALP on lipid metabolism in the liver. Mice were fed a high fat diet to cause diet-induced obesity (DIO) and then administered GALP intranasally for 2 weeks (experimental), or vehicle (control). Body weights, along with lipid levels in the plasma and liver, and lipid metabolism-related gene expression in the liver were subsequently measured. Body weight gain was decreased by the GALP treatment compared to the control group. Lipid droplet levels in hepatocytes and hepatic triglyceride levels were decreased in the GALP group compared with the vehicle group, whereas hepatic fatty acid β-oxidation-related gene mRNA levels were increased in the GALP group. These results suggest that the intranasal administration of GALP has an inhibitory effect on lipid accumulation in the liver.
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Galanin-Like Peptide Ameliorates Obesity by Control of Food Intake andEnergy Metabolism
Pharmaceutica Analytica Acta, 2014Co-Authors: Satoshi Hirako, Fumiko Takenoya, Nobuhiro Wada, Mai Okabe, Haruaki Kageyama, Seiji ShiodaAbstract:Galanin-Like Peptide (GALP) is a 60 amino acid neuroPeptide that was first isolated from the porcine hypothalamus. It is produced in the hypothalamic arcuate nucleus by neurons that form networks with other neurons containing Peptides involved in the control of feeding behavior. GALP plays an important role in the regulation of feeding, body weight and energy metabolism. Although the physiological actions of GALP are yet to be fully elucidated, it is possible, given the anti-obesity effect of GALP seen in relation to food intake and body weight loss in obese mice, that GALP could be applied clinically to combat obesity in humans. Here we summarize what is known about the regulation of energy metabolism by GALP, and describe results in animals that could possibly lead to the clinical use of GALP to treat obesity.
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Interactive effect of Galanin-Like Peptide (GALP) and spontaneous exercise on energy metabolism
Peptides, 2013Co-Authors: Haruaki Kageyama, Fumiko Takenoya, Satoshi Hirako, Tetsuro Ogawa, Lihua Wang, Seiji ShiodaAbstract:Abstract Galanin-Like Peptide (GALP) is a neuroPeptide involved in energy metabolism. The interactive effect of GALP and exercise on energy metabolism has not been investigated. The aim of this study was to determine if energy metabolism in spontaneously exercising mice could be promoted by intracerebroventricular (ICV) GALP administration. Changes in respiratory exchange ratio in response to GALP ICV administration indicated that lipids were primarily consumed followed by a continuous consumption of glucose throughout the dark period in non-exercising mice. In mice permitted to spontaneously exercise on a running-wheel, GALP ICV administration increased the consumed oxygen volume and heat production level from 5 to 11 h after administration. These effects occurred independently from the total running distance. The interaction between GALP ICV administration and spontaneous exercise decreased body weight within 24 h ( F (1,16) = 5.772, p F (1,16) = 18.602, p F (1,16) = 21.092, p p
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Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E_2 by Astrocytes in the Periventricular Zone of the Third Ventricle
Journal of Molecular Neuroscience, 2013Co-Authors: Haruaki Kageyama, Fumiko Takenoya, Mamiko Suzuki, Junichi Sakagami, Toshimasa Osaka, Kei Endo, Lihua Wang, Jun Watanabe, Seiji ShiodaAbstract:Administration of Galanin-Like Peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E_2 synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E_2-mediated pathway in astrocytes of the central nervous system.
Andrew L Gundlach - One of the best experts on this subject based on the ideXlab platform.
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Exaggerated feeding response to central Galanin-Like Peptide administration in diet-induced obese rats
Neuropeptides, 2005Co-Authors: Andrew L Gundlach, Margaret J MorrisAbstract:Abstract Galanin-Like Peptide (GALP) is a newly identified neuroPeptide implicated in the regulation of metabolism and reproduction. GALP gene expression is decreased in the hypothalamus of genetically obese rodents, such as fa / fa rats and ob / ob mice, and central administration of GALP increases feeding in satiated rats. The effect of dietary obesity on GALP-induced feeding is unknown, so this study characterized the effects of central administration of GALP on feeding in a rat model of diet-induced obesity. Male Sprague–Dawley rats ( n = 21) were randomly assigned to receive standard laboratory chow (12% fat as kcal) or high-fat cafeteria diet (35% fat) for 12 weeks before intracerebroventricular (icv) cannulae were implanted. Seven days later, rats received 0, 0.2 or 0.3 nmol doses of GALP in randomized order at least 48 h apart. Food intake was measured at 0.5, 1, 2, 4 and 24 h post administration and body weight was measured at 24 h. Rats were maintained on their respective diets throughout the entire feeding experiment. Implementation of the high-fat diet led to significantly greater caloric intake (230%) and body weight (28%) compared to chow-fed control rats. GALP-induced feeding was rapid and maximal in both dietary groups at 30 min post injection. The 0.3 nmol dose of GALP led to significantly larger increases in caloric intake in high-fat fed rats than in chow-fed controls (35.4 ± 3.7 and 22.1 ± 1.3 kcal, respectively, at 30 min). It is not known if diet-induced obesity alters endogenous GALP levels, but our data suggest that adaptive responses in GALP signaling might occur during chronic overfeeding. One possible explanation is an increased sensitivity and/or number of specific GALP receptors, although actions of exogenous GALP may also represent pharmacological actions at Galanin receptors.
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Galanin-Like Peptide mRNA Alterations in Arcuate Nucleus and Neural Lobe of Streptozotocin-Diabetic and Obese Zucker Rats
Neuroendocrinology, 2004Co-Authors: Jun Shen, Andrew L GundlachAbstract:Galanin-Like Peptide (GALP) is a 60-amino-acid Peptide with structural similarities to Galanin and a high affinity for Galanin receptors. GALP is expressed by a discrete population of neurons in the a
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Galanin-Like Peptide mRNA Alterations in Arcuate Nucleus and Neural Lobe of Streptozotocin-Diabetic and Obese Zucker Rats
Neuroendocrinology, 2004Co-Authors: Jun Shen, Andrew L GundlachAbstract:Galanin-Like Peptide (GALP) is a 60-amino-acid Peptide with structural similarities to Galanin and a high affinity for Galanin receptors. GALP is expressed by a discrete population of neurons in the arcuate nucleus (ARC) and median eminence of the hypothalamus of several species, including the rat. GALP neurons express leptin receptors and GALP mRNA levels are decreased slightly in fasted rats and stimulated significantly by acute leptin treatment in combination with fasting. In studies to further explore the leptin dependence of GALP expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and streptozotocin-induced diabetic (STZ-DM) rats. In leptin receptor-deficient obese Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels in the ARC were decreased by 75%, while neuroPeptide Y (NPY) mRNA levels were increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. In hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower body weight than controls, GALP mRNA levels in the ARC were decreased by 90%, while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). GALP is also expressed by pituicytes in the neural lobe of the rat pituitary gland and GALP expression is increased by osmotic stimulation such as dehydration and salt loading. Thus, in STZ-DM rats that are in a hyperosmotic state with elevated plasma vasopressin levels, GALP mRNA levels were increased by approximately 20-fold in the neural lobe relative to control (n = 4, p < 0.001). The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions, and possible abnormalities in GALP neuronal signalling and their putative targets, thyrotropin-releasing hormone and gonadotropin hormone-releasing hormone neurons, under pathophysiological conditions such as diabetes and obesity. Our data in STZ-DM rats also clearly demonstrate that GALP gene expression is differentially regulated in neurons and pituicytes.
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Galanin-Like Peptide mRNA in neural lobe of rat pituitary. Increased expression after osmotic stimulation suggests a role for Galanin-Like Peptide in neuron-glial interactions and/or neurosecretion.
Neuroendocrinology, 2001Co-Authors: Jun Shen, Jari A. Larm, Andrew L GundlachAbstract:Galanin-Like Peptide (GALP) was recently identified in the porcine hypothalamus, pituitary gland and gut, and has reported selectivity for the GalR2, c.f. the GalR1 receptor. GALP cDNAs have been cloned from pig, rat and human, and GALP mRNA expression is restricted to the arcuate nucleus in normal rat brain. This study examined the regional and cellular distribution of GALP mRNA in the rat pituitary gland, and subsequently determined the effect of osmotic stimulation on GALP transcript levels. GALP mRNA was not detected in the anterior or intermediate lobes, but moderate levels of GALP mRNA were present in the neural (posterior) lobe, in presumed pituicytes, of normal male and female rats. Osmotic stimulation by dehydration or salt loading produced a time-dependent increase in GALP mRNA levels in the neural lobe. Thus, dehydration for 4 days increased GALP mRNA 40-fold, while salt loading for 4, 7 or 10 days increased GALP levels 14-, 21- and 25-fold, respectively (p < or = 0.001). Levels of vasopressin (VP) mRNA in the neural lobe were also increased by these treatments, consistent with previous reports. Galanin (GAL) and GalR2 receptor mRNAs were not detected in the neural lobe, under normal or osmotic stimulation conditions. In addition, GALP mRNA levels in the arcuate nucleus were not altered in dehydrated or salt-loaded rats; and GALP mRNA was not detected in magnocellular neurons of the supraoptic or paraventricular nucleus, despite the characteristic up-regulation of VP and GAL mRNA in these cells. In view of the established anatomy and function of VP/oxytocin neurons in the hypothalamo-neurohypophysial system and the role played by pituicytes in their regulation, the Likely synthesis/release of GALP by these specialized astrocytes strongly suggests a role for this novel Peptide in regulation of pituicyte morphology/function and/or neurohormone release.
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Galanin-Like Peptide (GALP) mRNA Expression Is Restricted to Arcuate Nucleus of Hypothalamus in Adult Male Rat Brain
Neuroendocrinology, 2000Co-Authors: Jari A. Larm, Andrew L GundlachAbstract:Galanin-Like Peptide (GALP) is a novel 60-amino acid neuroPeptide, isolated from porcine hypothalamus and subsequently identified in rats and humans, which has reported selectivity for the Gal-R2 gala
