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Chronic blockade of brain IGF-I receptors suppresses food intake and estrous cyclicity in female rats
Abstracts / Frontiers in Neuroendocrinology 27 (2006) 4–11
or stereotypy activity (an indication of grooming behavior) as calculated by beam breaks in an activity monitor suggesting the animals were not suffering from nausea or general malaise. These findings further indicate that IMD may act through a unique receptor and support our hypothesis that IMD has a novel role in the maintenance of cardiovascular, fluid and energy homeostasis, distinct from those of AM or CGRP.
7
day 5. Serum leptin concentrations were significantly higher in JB-1 treated than in pair-fed animals at this time. We conclude that brain IGF-I receptor activation is necessary for normal compensatory hyperphagia and resumption of estrous cyclicity in female animals following a period of weight loss. (Supported by HD29856, T32 DK07513 and the Skirball Foundation.) doi:10.1016/j.yfrne.2006.03.015
doi:10.1016/j.yfrne.2006.03.014
Chronic blockade of brain IGF-I receptors suppresses food intake and estrous cyclicity in female rats Brigitte J. Todd a, Gary J. Schwartz b, Anne M. Etgen a,c a Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA b Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA c Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Dynamic regulation of gene expression in the dmpARC and ependymal layer in the Siberian hamster during seasonal weight change Perry Barrett a, Dana Wilson a, Julian G. Mercer a, Alexander W. Ross a, Lynn Bell a, Francis J.P. Ebling b, Alex Schuhler b, Peter J. Morgan a a Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK b School of Biomedical Sciences, University of Nottingham, NG7 2UH, UK
Insulin-like growth factor-I (IGF-I) receptor activation is a key component of many neuroendocrine processes, and circulating IGF-I levels are highly sensitive to changes in metabolic state. To test the hypothesis that brain IGF-I signaling integrates energy balance and reproduction in females, we investigated the effects of chronic blockade of brain IGF-I receptors in gonadally intact female rats. Food intake, body weight, and estrous cyclicity were monitored for 7–14 days while a selective IGF-I receptor antagonist (JB-1) or vehicle (controls) was delivered into the third ventricle via an osmotic minipump (20 lg/ml, 0.5 ll/h). Surgical placement of the osmotic minipump resulted in a temporary reduction of food intake, an approximately 10% loss of body weight and disruption of estrous cyclicity in all animals. Control females engaged in compensatory hyperphagia for 5–7 days following surgery, until pre-surgical body weight was regained. By contrast, animals infused with the IGF-I receptor antagonist JB-1 did not exhibit compensatory hyperphagia or return to pre-surgical body weight even after 14 days. Furthermore, control animals resumed normal estrous cycles (4.5 ± 1.46 days postsurgery) significantly earlier than JB-1 treated rats (8.6 ± 0.92 days; p < 0.05). When control animals were pair-fed to the level of JB-1 treated animals for 7 days, regain of body weight was even slower than in JB-1 treated females. Upon resumption of ad-lib feeding, pair-fed females exhibited compensatory hyperphagia and a rapid resumption of pre-surgical body weight and estrous cyclicity. JB-1 treated animals did not exhibit compensatory hyperphagia when drug treatment was terminated after 7 days, and they did not resume estrous cycles as quickly as pair-fed females. Serum insulin and glucose concentrations were not significantly different among ad-lib fed control, ad-lib fed JB-1, and pair-fed control groups on
Physiological and behavioural adaptations of the Siberian hamster which occur as part of a strategy to survive environmental changes encountered in winter include a reduction in food intake and loss of body fat accounting for 30–40% of body weight. Seasonal body weight loss offers the advantage of a physiological model of body weight regulation as opposed to an enforced or manipulated loss through dietary, pharmacological or genomic intervention. Using several approaches, we are investigating the mechanism by which the hamster achieves this dramatic weight loss. A microarray and a candidate gene approach, coupled with in situ hybridization, have uncovered photoperiod-regulated gene expression in the dorsal medial posterior arcuate nucleus (dmpARC). Recent advances reveal the dynamic responses of the dmpARC to photoperiod, with several genes up-regulated during the period of weight loss. These include the melanocortin 3 receptor and the immediate early gene c-fos, implicating significant activation of neurons in the dmpARC in short days (SD). Noteworthy is the constitutive presence of c-fos both at the level of mRNA and protein in the dmpARC of SD hamsters. In the context of the SD increase seen in VGF mRNA (a gene implicated in energy balance), the data points to a very important role for the dmpARC in mediating body weight and other seasonal responses. Dual in situ hybridization reveals that c-fos and VGF are co-expressed. In addition to the dmpARC, we have uncovered photoperiodic regulation of several mRNA sequences in the ependymal layer of the third ventricle adjacent to the arcuate nucleus and dmpARC. These include the orphan G protein coupled receptor GPR50, the intermediate filament protein, Nestin, and the retinoic acid binding protein
or stereotypy activity (an indication of grooming behavior) as calculated by beam breaks in an activity monitor suggesting the animals were not suffering from nausea or general malaise. These findings further indicate that IMD may act through a unique receptor and support our hypothesis that IMD has a novel role in the maintenance of cardiovascular, fluid and energy homeostasis, distinct from those of AM or CGRP.
7
day 5. Serum leptin concentrations were significantly higher in JB-1 treated than in pair-fed animals at this time. We conclude that brain IGF-I receptor activation is necessary for normal compensatory hyperphagia and resumption of estrous cyclicity in female animals following a period of weight loss. (Supported by HD29856, T32 DK07513 and the Skirball Foundation.) doi:10.1016/j.yfrne.2006.03.015
doi:10.1016/j.yfrne.2006.03.014
Chronic blockade of brain IGF-I receptors suppresses food intake and estrous cyclicity in female rats Brigitte J. Todd a, Gary J. Schwartz b, Anne M. Etgen a,c a Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA b Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA c Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Dynamic regulation of gene expression in the dmpARC and ependymal layer in the Siberian hamster during seasonal weight change Perry Barrett a, Dana Wilson a, Julian G. Mercer a, Alexander W. Ross a, Lynn Bell a, Francis J.P. Ebling b, Alex Schuhler b, Peter J. Morgan a a Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK b School of Biomedical Sciences, University of Nottingham, NG7 2UH, UK
Insulin-like growth factor-I (IGF-I) receptor activation is a key component of many neuroendocrine processes, and circulating IGF-I levels are highly sensitive to changes in metabolic state. To test the hypothesis that brain IGF-I signaling integrates energy balance and reproduction in females, we investigated the effects of chronic blockade of brain IGF-I receptors in gonadally intact female rats. Food intake, body weight, and estrous cyclicity were monitored for 7–14 days while a selective IGF-I receptor antagonist (JB-1) or vehicle (controls) was delivered into the third ventricle via an osmotic minipump (20 lg/ml, 0.5 ll/h). Surgical placement of the osmotic minipump resulted in a temporary reduction of food intake, an approximately 10% loss of body weight and disruption of estrous cyclicity in all animals. Control females engaged in compensatory hyperphagia for 5–7 days following surgery, until pre-surgical body weight was regained. By contrast, animals infused with the IGF-I receptor antagonist JB-1 did not exhibit compensatory hyperphagia or return to pre-surgical body weight even after 14 days. Furthermore, control animals resumed normal estrous cycles (4.5 ± 1.46 days postsurgery) significantly earlier than JB-1 treated rats (8.6 ± 0.92 days; p < 0.05). When control animals were pair-fed to the level of JB-1 treated animals for 7 days, regain of body weight was even slower than in JB-1 treated females. Upon resumption of ad-lib feeding, pair-fed females exhibited compensatory hyperphagia and a rapid resumption of pre-surgical body weight and estrous cyclicity. JB-1 treated animals did not exhibit compensatory hyperphagia when drug treatment was terminated after 7 days, and they did not resume estrous cycles as quickly as pair-fed females. Serum insulin and glucose concentrations were not significantly different among ad-lib fed control, ad-lib fed JB-1, and pair-fed control groups on
Physiological and behavioural adaptations of the Siberian hamster which occur as part of a strategy to survive environmental changes encountered in winter include a reduction in food intake and loss of body fat accounting for 30–40% of body weight. Seasonal body weight loss offers the advantage of a physiological model of body weight regulation as opposed to an enforced or manipulated loss through dietary, pharmacological or genomic intervention. Using several approaches, we are investigating the mechanism by which the hamster achieves this dramatic weight loss. A microarray and a candidate gene approach, coupled with in situ hybridization, have uncovered photoperiod-regulated gene expression in the dorsal medial posterior arcuate nucleus (dmpARC). Recent advances reveal the dynamic responses of the dmpARC to photoperiod, with several genes up-regulated during the period of weight loss. These include the melanocortin 3 receptor and the immediate early gene c-fos, implicating significant activation of neurons in the dmpARC in short days (SD). Noteworthy is the constitutive presence of c-fos both at the level of mRNA and protein in the dmpARC of SD hamsters. In the context of the SD increase seen in VGF mRNA (a gene implicated in energy balance), the data points to a very important role for the dmpARC in mediating body weight and other seasonal responses. Dual in situ hybridization reveals that c-fos and VGF are co-expressed. In addition to the dmpARC, we have uncovered photoperiodic regulation of several mRNA sequences in the ependymal layer of the third ventricle adjacent to the arcuate nucleus and dmpARC. These include the orphan G protein coupled receptor GPR50, the intermediate filament protein, Nestin, and the retinoic acid binding protein