The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform
Shin Hasegawa - One of the best experts on this subject based on the ideXlab platform.
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Corticotropin-releasing factor is a downstream mediator of the Beta-Melanocyte-Stimulating Hormone-induced anorexigenic pathway in chicks.
Neuroscience letters, 2009Co-Authors: Hiroshi Kamisoyama, Kazuhisa Honda, Takaoki Saneyasu, Kunio Sugahara, Shin HasegawaAbstract:Proopiomelanocortin (POMC, a precursor of anorexigenic neuropeptides) neurons in hypothalamus suppresses food intake in both mammals and chickens. In mammals, several lines of evidence suggest that POMC-derived anorexigenic peptides upregulate mRNA levels of anorexigenic peptides such as corticotropin-releasing factor (CRF) and thyrotropin-releasing factor and downregulate mRNA levels of orexigenic peptides such as orexin and melanin-concentrating Hormone. However, the POMC-induced anorexigenic pathway in chickens has not been well characterized. In the present study, we investigated how POMC neurons regulate mechanisms of food intake using an anorexigenic peptide, Beta-Melanocyte-Stimulating Hormone (β-MSH), derived from the post-transcriptional cleavage of POMC. Central administration of β-MSH in chicks significantly suppressed food intake, and importantly, this suppression was accompanied by a significant upregulation of CRF mRNA levels. Furthermore, the CRF type 2 receptor antagonist alpha-helical CRF significantly reversed the anorexigenic action of β-MSH. These findings indicate that CRF and its receptor, CRF type 2 receptor, act as the major mediators in β-MSH-induced anorexigenic action in chicks. β-MSH significantly increased orexin mRNA levels and did not alter mRNA levels of thyrotropin-releasing factor and melanin-concentrating Hormone in chicks, suggesting that the β-MSH-induced anorexigenic pathway in chicks is different from that in mammals. Increases in orexin mRNA levels were accompanied by significant decreases in plasma glucose concentration, suggesting that orexin mRNA might be stimulated by β-MSH-induced hypoglycemia. Thus, this study demonstrates the direct evidence that CRF is a critical downstream target in the β-MSH-induced anorexigenic pathway in chicks.
Mark A. Cline - One of the best experts on this subject based on the ideXlab platform.
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The anorexigenic effect of Beta-Melanocyte-Stimulating Hormone involves corticotrophin-releasing factor and mesotocin in birds.
Neuroscience letters, 2020Co-Authors: Chang Cao, Elizabeth R. Gilbert, Mark A. ClineAbstract:Abstract Beta-Melanocyte-Stimulating Hormone (β-MSH), when centrally injected, induces anorexigenic effects in rodents and chickens but its mechanism remains unclear. Thus, the primary goal of this research was to elucidate the hypothalamic mechanism using chickens. Intracerebroventricular injection of 0.3, 1.0 and 3.0 nmol of β-MSH decreased food intake for 540 min. Expression of hypothalamic mRNAs were affected by β-MSH injection, including corticotrophin-releasing factor (CRF) and its receptor subtype 1 (CRFR1), mesotocin (MT) and its receptor (MTR), pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript (CART), growth Hormone secretagogue receptor (GHSR) and neuropeptide Y (NPY) receptor subtype 5 (NPYR5). Within the arcuate nucleus, expressions of NPY, agouti-related peptide, MT and MTR were increased by β-MSH injection. β-MSH-treated chicks had more CRF, CRFR1, CRF receptor subtype 2, GHSR, NPY receptor subtype 1 (NPYR1) and NPYR5 mRNA but lower levels of CART and ghrelin, in the paraventricular nucleus. Greater amounts of mRNA for MTR, GHSR, NPYR1 and NPYR5 and less CRF expression were observed in the ventromedial hypothalamus. In conclusion, central injection of β-MSH potently reduced food intake and was associated with changes in mRNA expression of some anorexigenic factors in a hypothalamic nucleus-specific manner.
Julia M. Keogh - One of the best experts on this subject based on the ideXlab platform.
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A POMC variant implicates Beta-Melanocyte-Stimulating Hormone in the control of human energy balance.
Cell metabolism, 2006Co-Authors: Yung Seng Lee, Ben Challis, Darren A. Thompson, Giles S.h. Yeo, Julia M. Keogh, Michael E. Madonna, Vicki Wraight, Matthew A. Sims, Vincent Vatin, David MeyreAbstract:The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta-MSH, the majority of attention has focused on alpha-MSH, partly reflecting the absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding beta-MSH, Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the general UK Caucasian population and the variant cosegregated with obesity/overweight in affected family members. Compared to wild-type beta-MSH, the variant peptide was impaired in its ability to bind to and activate signaling from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for beta-MSH in the control of human energy homeostasis.
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A missense mutation disrupting a dibasic proHormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism
Human molecular genetics, 2002Co-Authors: Benjamin G. Challis, Giles S.h. Yeo, Julia M. Keogh, Lynn E. Pritchard, John W.m. Creemers, Jérôme Delplanque, Jian'an Luan, Nicholas J. Wareham, Sumit Bhattacharyya, Phillipe FroguelAbstract:The functional loss of both alleles of the human pro-opiomelanocortin (POMC) gene leads to a very rare syndrome of hypoadrenalism, red hair and early-onset obesity. In order to examine whether more subtle genetic variants in POMC might contribute to early-onset obesity, the coding region of the gene was sequenced in 262 Caucasian subjects with a history of severe obesity from childhood. Two children were found to be heterozygous for a missense mutation, R236G, which disrupts the dibasic cleavage site between beta melanocyte-stimulating Hormone (beta-MSH) and beta-endorphin. Beta-TC3 cells transfected with the mutant POMC cDNA produced a mutant beta-MSH/beta-endorphin fusion protein. This fusion protein bound to the human melanocortin-4 receptor (hMC4R) with an affinity similar to its natural ligands, but had a markedly reduced ability to activate the receptor. This variant co-segregated with early-onset obesity over three generations in one family and was absent in 412 normal weight UK Caucasian controls. Combining the results in UK Caucasians with a new case-control study in French subjects and three previously published reports, mutations disrupting this processing site were present in 0.88% of subjects with early-onset obesity and 0.22% of normal-weight controls. These results suggest that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signalling.
Giles S.h. Yeo - One of the best experts on this subject based on the ideXlab platform.
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A POMC variant implicates Beta-Melanocyte-Stimulating Hormone in the control of human energy balance.
Cell metabolism, 2006Co-Authors: Yung Seng Lee, Ben Challis, Darren A. Thompson, Giles S.h. Yeo, Julia M. Keogh, Michael E. Madonna, Vicki Wraight, Matthew A. Sims, Vincent Vatin, David MeyreAbstract:The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta-MSH, the majority of attention has focused on alpha-MSH, partly reflecting the absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding beta-MSH, Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the general UK Caucasian population and the variant cosegregated with obesity/overweight in affected family members. Compared to wild-type beta-MSH, the variant peptide was impaired in its ability to bind to and activate signaling from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for beta-MSH in the control of human energy homeostasis.
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A missense mutation disrupting a dibasic proHormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism
Human molecular genetics, 2002Co-Authors: Benjamin G. Challis, Giles S.h. Yeo, Julia M. Keogh, Lynn E. Pritchard, John W.m. Creemers, Jérôme Delplanque, Jian'an Luan, Nicholas J. Wareham, Sumit Bhattacharyya, Phillipe FroguelAbstract:The functional loss of both alleles of the human pro-opiomelanocortin (POMC) gene leads to a very rare syndrome of hypoadrenalism, red hair and early-onset obesity. In order to examine whether more subtle genetic variants in POMC might contribute to early-onset obesity, the coding region of the gene was sequenced in 262 Caucasian subjects with a history of severe obesity from childhood. Two children were found to be heterozygous for a missense mutation, R236G, which disrupts the dibasic cleavage site between beta melanocyte-stimulating Hormone (beta-MSH) and beta-endorphin. Beta-TC3 cells transfected with the mutant POMC cDNA produced a mutant beta-MSH/beta-endorphin fusion protein. This fusion protein bound to the human melanocortin-4 receptor (hMC4R) with an affinity similar to its natural ligands, but had a markedly reduced ability to activate the receptor. This variant co-segregated with early-onset obesity over three generations in one family and was absent in 412 normal weight UK Caucasian controls. Combining the results in UK Caucasians with a new case-control study in French subjects and three previously published reports, mutations disrupting this processing site were present in 0.88% of subjects with early-onset obesity and 0.22% of normal-weight controls. These results suggest that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signalling.
David Meyre - One of the best experts on this subject based on the ideXlab platform.
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A POMC variant implicates Beta-Melanocyte-Stimulating Hormone in the control of human energy balance.
Cell metabolism, 2006Co-Authors: Yung Seng Lee, Ben Challis, Darren A. Thompson, Giles S.h. Yeo, Julia M. Keogh, Michael E. Madonna, Vicki Wraight, Matthew A. Sims, Vincent Vatin, David MeyreAbstract:The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta-MSH, the majority of attention has focused on alpha-MSH, partly reflecting the absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding beta-MSH, Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the general UK Caucasian population and the variant cosegregated with obesity/overweight in affected family members. Compared to wild-type beta-MSH, the variant peptide was impaired in its ability to bind to and activate signaling from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for beta-MSH in the control of human energy homeostasis.