The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Xu-feng Huang - One of the best experts on this subject based on the ideXlab platform.
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Hypothalamic histamine H1 receptor-AMPK signaling time-dependently mediates olanzapine-induced Hyperphagia and weight gain in female rats.
Psychoneuroendocrinology, 2014Co-Authors: Qingsheng Zhang, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-feng HuangAbstract:Although second-generation antipsychotics induce severe weight gain and obesity, there is a lack of detailed knowledge about the progressive development of antipsychotic-induced obesity. This study examined the hypothalamic histamine H1 receptor and AMP-activated protein kinase (H1R-AMPK) signaling at three distinctive stages of olanzapine-induced weight gain (day 1-12: early acceleration, day 13-28: middle new equilibrium, and day 29-36: late heavy weight maintenance). At the early acceleration stage, the rats were hyperphagic with an underlying mechanism of olanzapine-increased H1R mRNA expression and AMPK phosphorylation (pAMPK), in which pAMPK levels positively correlated with H1R mRNA expression and food intake. At the middle stage, when the rats were no longer hyperphagic, the changes in H1R-AMPK signaling vanished. At the late stage, olanzapine increased H1R mRNA expression but decreased pAMPK which were positively and negatively correlated with weight gain, respectively. These data suggest a time-dependent change of H1R-AMPK signaling, where olanzapine activates AMPK by blocking the H1Rs and causing Hyperphagia in the acute phase. The chronic blockade of H1R may contribute to the late stage of olanzapine-induced heavy weight maintenance. However, pAMPK was no longer elevated and actually decreased. This indicates that AMPK acts as an energy sensor and negatively responds to the positive energy balance induced by olanzapine. Furthermore, we showed that an H1R agonist, 2-(3-trifluoromethylphenyl) histamine, can significantly inhibit olanzapine-induced Hyperphagia and AMPK activation in the mediobasal hypothalamus in a dose dependent manner. Therefore, lowering H1R-AMPK signaling is an effective treatment for the olanzapine-induced Hyperphagia associated with the development of obesity.
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Hypothalamic ghrelin signalling mediates olanzapine-induced Hyperphagia and weight gain in female rats
The international journal of neuropsychopharmacology, 2014Co-Authors: Qingsheng Zhang, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-feng HuangAbstract:Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and Hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced Hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to Hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in Hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from Hyperphagia.
Elizabeth Roof - One of the best experts on this subject based on the ideXlab platform.
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assessment of Hyperphagia in prader willi syndrome
Obesity, 2007Co-Authors: Elisabeth M. Dykens, Melissa A. Maxwell, Elizabeth Pantino, Rebecca Kossler, Elizabeth RoofAbstract:Objective: Prader-Willi syndrome (PWS), the leading known genetic cause of obesity, is characterized by intellectual disabilities, maladaptive and compulsive behaviors, and Hyperphagia. Although complications of obesity resulting from Hyperphagia are the leading cause of death in PWS, quantifying this drive for food has long been an unmet research need. This study provides factor-analytic and within-syndrome analyses of a new measure of Hyperphagia in PWS. Research Methods and Procedure: A 13-item informant measure, the Hyperphagia Questionnaire, was developed and administered to the parents of 153 persons with PWS, 4 to 51 years of age. The intelligence quotients, genetic subtypes of PWS, and BMIs of offspring were obtained, as were measures of their non-food problem behaviors. Results: Factor analyses with varimax rotation produced three statistically and conceptually robust factors that accounted for 59% of the variance: Hyperphagic Behaviors, Drive, and Severity. Hyperphagic Behavior increased with age, whereas Drive remained stable, and Severity dipped in older adults. Hyperphagic Drive and Severity were positively correlated with non-food behavior problems, and Hyperphagic Drive differentiated the 36% of participants with extreme obesity from those who had overweight/obese (48%) or healthy (16%) BMI classifications. Discussion: The Hyperphagia Questionnaire is a robust tool for relating breakthroughs in the neurobiology of Hyperphagia to in vivo food-seeking behavior and for examining the psychological and developmental correlates of Hyperphagia in PWS. The Hyperphagia Questionnaire also offers a nuanced, real-life outcome measure for future clinical trials aimed at curbing the life-threatening drive for food in PWS.
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Assessment of Hyperphagia in Prader‐Willi Syndrome
Obesity (Silver Spring Md.), 2007Co-Authors: Elisabeth M. Dykens, Melissa A. Maxwell, Elizabeth Pantino, Rebecca Kossler, Elizabeth RoofAbstract:Objective: Prader-Willi syndrome (PWS), the leading known genetic cause of obesity, is characterized by intellectual disabilities, maladaptive and compulsive behaviors, and Hyperphagia. Although complications of obesity resulting from Hyperphagia are the leading cause of death in PWS, quantifying this drive for food has long been an unmet research need. This study provides factor-analytic and within-syndrome analyses of a new measure of Hyperphagia in PWS. Research Methods and Procedure: A 13-item informant measure, the Hyperphagia Questionnaire, was developed and administered to the parents of 153 persons with PWS, 4 to 51 years of age. The intelligence quotients, genetic subtypes of PWS, and BMIs of offspring were obtained, as were measures of their non-food problem behaviors. Results: Factor analyses with varimax rotation produced three statistically and conceptually robust factors that accounted for 59% of the variance: Hyperphagic Behaviors, Drive, and Severity. Hyperphagic Behavior increased with age, whereas Drive remained stable, and Severity dipped in older adults. Hyperphagic Drive and Severity were positively correlated with non-food behavior problems, and Hyperphagic Drive differentiated the 36% of participants with extreme obesity from those who had overweight/obese (48%) or healthy (16%) BMI classifications. Discussion: The Hyperphagia Questionnaire is a robust tool for relating breakthroughs in the neurobiology of Hyperphagia to in vivo food-seeking behavior and for examining the psychological and developmental correlates of Hyperphagia in PWS. The Hyperphagia Questionnaire also offers a nuanced, real-life outcome measure for future clinical trials aimed at curbing the life-threatening drive for food in PWS.
Joel K Elmquist - One of the best experts on this subject based on the ideXlab platform.
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the atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2c
Journal of Clinical Investigation, 2017Co-Authors: Caleb C Lord, Steven C Wyler, Carlos M Castorena, Newaz Ahmed, Dias Mathew, Joel K ElmquistAbstract:: Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced Hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced Hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced Hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.
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Hyperphagia: current concepts and future directions proceedings of the 2nd international conference on Hyperphagia.
Obesity, 2014Co-Authors: Steven B. Heymsfield, George A Bray, Nicole M. Avena, Leslie J. Baier, Phillip J. Brantley, Lisa Cole Burnett, Merlin G. Butler, Daniel J. Driscoll, Dieter Egli, Joel K ElmquistAbstract:Objective Hyperphagia is a central feature of inherited disorders (e.g., Prader–Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms and treatments. Substantial gaps in understanding the molecular basis of inherited Hyperphagia syndromes are present as are a lack of mechanistic of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments. Design and Methods International conference with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates. Results The reviewed collective research and clinical experience provides a critical body of new and novel information on Hyperphagia at levels ranging from molecular to population. Gaps in understanding and tools needed for additional research were identified. Conclusions This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of Hyperphagia and identifies key areas for future funding and research.
Qingsheng Zhang - One of the best experts on this subject based on the ideXlab platform.
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Hypothalamic histamine H1 receptor-AMPK signaling time-dependently mediates olanzapine-induced Hyperphagia and weight gain in female rats.
Psychoneuroendocrinology, 2014Co-Authors: Qingsheng Zhang, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-feng HuangAbstract:Although second-generation antipsychotics induce severe weight gain and obesity, there is a lack of detailed knowledge about the progressive development of antipsychotic-induced obesity. This study examined the hypothalamic histamine H1 receptor and AMP-activated protein kinase (H1R-AMPK) signaling at three distinctive stages of olanzapine-induced weight gain (day 1-12: early acceleration, day 13-28: middle new equilibrium, and day 29-36: late heavy weight maintenance). At the early acceleration stage, the rats were hyperphagic with an underlying mechanism of olanzapine-increased H1R mRNA expression and AMPK phosphorylation (pAMPK), in which pAMPK levels positively correlated with H1R mRNA expression and food intake. At the middle stage, when the rats were no longer hyperphagic, the changes in H1R-AMPK signaling vanished. At the late stage, olanzapine increased H1R mRNA expression but decreased pAMPK which were positively and negatively correlated with weight gain, respectively. These data suggest a time-dependent change of H1R-AMPK signaling, where olanzapine activates AMPK by blocking the H1Rs and causing Hyperphagia in the acute phase. The chronic blockade of H1R may contribute to the late stage of olanzapine-induced heavy weight maintenance. However, pAMPK was no longer elevated and actually decreased. This indicates that AMPK acts as an energy sensor and negatively responds to the positive energy balance induced by olanzapine. Furthermore, we showed that an H1R agonist, 2-(3-trifluoromethylphenyl) histamine, can significantly inhibit olanzapine-induced Hyperphagia and AMPK activation in the mediobasal hypothalamus in a dose dependent manner. Therefore, lowering H1R-AMPK signaling is an effective treatment for the olanzapine-induced Hyperphagia associated with the development of obesity.
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Hypothalamic ghrelin signalling mediates olanzapine-induced Hyperphagia and weight gain in female rats
The international journal of neuropsychopharmacology, 2014Co-Authors: Qingsheng Zhang, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-feng HuangAbstract:Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and Hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced Hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to Hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in Hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from Hyperphagia.
Elisabeth M. Dykens - One of the best experts on this subject based on the ideXlab platform.
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assessment of Hyperphagia in prader willi syndrome
Obesity, 2007Co-Authors: Elisabeth M. Dykens, Melissa A. Maxwell, Elizabeth Pantino, Rebecca Kossler, Elizabeth RoofAbstract:Objective: Prader-Willi syndrome (PWS), the leading known genetic cause of obesity, is characterized by intellectual disabilities, maladaptive and compulsive behaviors, and Hyperphagia. Although complications of obesity resulting from Hyperphagia are the leading cause of death in PWS, quantifying this drive for food has long been an unmet research need. This study provides factor-analytic and within-syndrome analyses of a new measure of Hyperphagia in PWS. Research Methods and Procedure: A 13-item informant measure, the Hyperphagia Questionnaire, was developed and administered to the parents of 153 persons with PWS, 4 to 51 years of age. The intelligence quotients, genetic subtypes of PWS, and BMIs of offspring were obtained, as were measures of their non-food problem behaviors. Results: Factor analyses with varimax rotation produced three statistically and conceptually robust factors that accounted for 59% of the variance: Hyperphagic Behaviors, Drive, and Severity. Hyperphagic Behavior increased with age, whereas Drive remained stable, and Severity dipped in older adults. Hyperphagic Drive and Severity were positively correlated with non-food behavior problems, and Hyperphagic Drive differentiated the 36% of participants with extreme obesity from those who had overweight/obese (48%) or healthy (16%) BMI classifications. Discussion: The Hyperphagia Questionnaire is a robust tool for relating breakthroughs in the neurobiology of Hyperphagia to in vivo food-seeking behavior and for examining the psychological and developmental correlates of Hyperphagia in PWS. The Hyperphagia Questionnaire also offers a nuanced, real-life outcome measure for future clinical trials aimed at curbing the life-threatening drive for food in PWS.
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Assessment of Hyperphagia in Prader‐Willi Syndrome
Obesity (Silver Spring Md.), 2007Co-Authors: Elisabeth M. Dykens, Melissa A. Maxwell, Elizabeth Pantino, Rebecca Kossler, Elizabeth RoofAbstract:Objective: Prader-Willi syndrome (PWS), the leading known genetic cause of obesity, is characterized by intellectual disabilities, maladaptive and compulsive behaviors, and Hyperphagia. Although complications of obesity resulting from Hyperphagia are the leading cause of death in PWS, quantifying this drive for food has long been an unmet research need. This study provides factor-analytic and within-syndrome analyses of a new measure of Hyperphagia in PWS. Research Methods and Procedure: A 13-item informant measure, the Hyperphagia Questionnaire, was developed and administered to the parents of 153 persons with PWS, 4 to 51 years of age. The intelligence quotients, genetic subtypes of PWS, and BMIs of offspring were obtained, as were measures of their non-food problem behaviors. Results: Factor analyses with varimax rotation produced three statistically and conceptually robust factors that accounted for 59% of the variance: Hyperphagic Behaviors, Drive, and Severity. Hyperphagic Behavior increased with age, whereas Drive remained stable, and Severity dipped in older adults. Hyperphagic Drive and Severity were positively correlated with non-food behavior problems, and Hyperphagic Drive differentiated the 36% of participants with extreme obesity from those who had overweight/obese (48%) or healthy (16%) BMI classifications. Discussion: The Hyperphagia Questionnaire is a robust tool for relating breakthroughs in the neurobiology of Hyperphagia to in vivo food-seeking behavior and for examining the psychological and developmental correlates of Hyperphagia in PWS. The Hyperphagia Questionnaire also offers a nuanced, real-life outcome measure for future clinical trials aimed at curbing the life-threatening drive for food in PWS.
