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The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus

Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin’s anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to dec...

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Autores principales: Dodd, Garron T., Worth, Amy A., Nunn, Nicolas, Korpal, Aaron K., Bechtold, David A., Allison, Margaret B., Myers, Martin G., Statnick, Michael A., Luckman, Simon M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192552/
https://www.ncbi.nlm.nih.gov/pubmed/25176149
http://dx.doi.org/10.1016/j.cmet.2014.07.022
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author Dodd, Garron T.
Worth, Amy A.
Nunn, Nicolas
Korpal, Aaron K.
Bechtold, David A.
Allison, Margaret B.
Myers, Martin G.
Statnick, Michael A.
Luckman, Simon M.
author_facet Dodd, Garron T.
Worth, Amy A.
Nunn, Nicolas
Korpal, Aaron K.
Bechtold, David A.
Allison, Margaret B.
Myers, Martin G.
Statnick, Michael A.
Luckman, Simon M.
author_sort Dodd, Garron T.
collection PubMed
description Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin’s anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin.
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spelling pubmed-41925522014-10-13 The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus Dodd, Garron T. Worth, Amy A. Nunn, Nicolas Korpal, Aaron K. Bechtold, David A. Allison, Margaret B. Myers, Martin G. Statnick, Michael A. Luckman, Simon M. Cell Metab Article Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin’s anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin. Cell Press 2014-10-07 /pmc/articles/PMC4192552/ /pubmed/25176149 http://dx.doi.org/10.1016/j.cmet.2014.07.022 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) .
spellingShingle Article
Dodd, Garron T.
Worth, Amy A.
Nunn, Nicolas
Korpal, Aaron K.
Bechtold, David A.
Allison, Margaret B.
Myers, Martin G.
Statnick, Michael A.
Luckman, Simon M.
The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus
title The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus
title_full The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus
title_fullStr The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus
title_full_unstemmed The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus
title_short The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus
title_sort thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192552/
https://www.ncbi.nlm.nih.gov/pubmed/25176149
http://dx.doi.org/10.1016/j.cmet.2014.07.022
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