Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level

Autores
Perello, Mario; Çakir, Isin; Cyr, Nicole E.; Romero, Amparo; Stuart, Ronald, C.; Chiappini, Franck; Hollenberg , Anthony N.; Nillni, Eduardo A.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T4/3 seen in obese animals is due mostly to central leptin action. We also found that T 3 feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T3 and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity.
Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Çakir, Isin. University Brown; Estados Unidos
Fil: Cyr, Nicole E.. University Brown; Estados Unidos
Fil: Romero, Amparo. University Brown; Estados Unidos
Fil: Stuart, Ronald, C.. University Brown; Estados Unidos
Fil: Chiappini, Franck. Beth Israel Deaconess Medical Center; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Hollenberg , Anthony N.. Beth Israel Deaconess Medical Center; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Nillni, Eduardo A.. University Brown; Estados Unidos
Materia
LEPTIN
THYROID AXIS
OBESITY
HYPOTHALAMIC-PITUITARY-THYROID
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/85916
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/85916
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central levelPerello, MarioÇakir, IsinCyr, Nicole E.Romero, AmparoStuart, Ronald, C.Chiappini, FranckHollenberg , Anthony N.Nillni, Eduardo A.LEPTINTHYROID AXISOBESITYHYPOTHALAMIC-PITUITARY-THYROIDhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T4/3 seen in obese animals is due mostly to central leptin action. We also found that T 3 feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T3 and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity.Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Çakir, Isin. University Brown; Estados UnidosFil: Cyr, Nicole E.. University Brown; Estados UnidosFil: Romero, Amparo. University Brown; Estados UnidosFil: Stuart, Ronald, C.. University Brown; Estados UnidosFil: Chiappini, Franck. Beth Israel Deaconess Medical Center; Estados Unidos. Harvard Medical School; Estados UnidosFil: Hollenberg , Anthony N.. Beth Israel Deaconess Medical Center; Estados Unidos. Harvard Medical School; Estados UnidosFil: Nillni, Eduardo A.. University Brown; Estados UnidosAmerican Physiological Society2010-12-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85916Perello, Mario; Çakir, Isin; Cyr, Nicole E.; Romero, Amparo; Stuart, Ronald, C.; et al.; Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 299; 6; 5-12-2010; E976-E9890193-1849CONICET DigitalCONICETenginfo:eu-repo/semantics/reference/doi/https://doi.org/10.1152/ajpendo.zh1-6178-corr.2011info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00448.2010info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajpendo.00448.2010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:16Zoai:ri.conicet.gov.ar:11336/85916instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:48:16.857CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
title Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
spellingShingle Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
Perello, Mario
LEPTIN
THYROID AXIS
OBESITY
HYPOTHALAMIC-PITUITARY-THYROID
title_short Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
title_full Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
title_fullStr Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
title_full_unstemmed Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
title_sort Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level
dc.creator.none.fl_str_mv Perello, Mario
Çakir, Isin
Cyr, Nicole E.
Romero, Amparo
Stuart, Ronald, C.
Chiappini, Franck
Hollenberg , Anthony N.
Nillni, Eduardo A.
author Perello, Mario
author_facet Perello, Mario
Çakir, Isin
Cyr, Nicole E.
Romero, Amparo
Stuart, Ronald, C.
Chiappini, Franck
Hollenberg , Anthony N.
Nillni, Eduardo A.
author_role author
author2 Çakir, Isin
Cyr, Nicole E.
Romero, Amparo
Stuart, Ronald, C.
Chiappini, Franck
Hollenberg , Anthony N.
Nillni, Eduardo A.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LEPTIN
THYROID AXIS
OBESITY
HYPOTHALAMIC-PITUITARY-THYROID
topic LEPTIN
THYROID AXIS
OBESITY
HYPOTHALAMIC-PITUITARY-THYROID
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T4/3 seen in obese animals is due mostly to central leptin action. We also found that T 3 feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T3 and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity.
Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Çakir, Isin. University Brown; Estados Unidos
Fil: Cyr, Nicole E.. University Brown; Estados Unidos
Fil: Romero, Amparo. University Brown; Estados Unidos
Fil: Stuart, Ronald, C.. University Brown; Estados Unidos
Fil: Chiappini, Franck. Beth Israel Deaconess Medical Center; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Hollenberg , Anthony N.. Beth Israel Deaconess Medical Center; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Nillni, Eduardo A.. University Brown; Estados Unidos
description The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T4/3 seen in obese animals is due mostly to central leptin action. We also found that T 3 feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T3 and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity.
publishDate 2010
dc.date.none.fl_str_mv 2010-12-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/85916
Perello, Mario; Çakir, Isin; Cyr, Nicole E.; Romero, Amparo; Stuart, Ronald, C.; et al.; Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 299; 6; 5-12-2010; E976-E989
0193-1849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85916
identifier_str_mv Perello, Mario; Çakir, Isin; Cyr, Nicole E.; Romero, Amparo; Stuart, Ronald, C.; et al.; Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 299; 6; 5-12-2010; E976-E989
0193-1849
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/doi/https://doi.org/10.1152/ajpendo.zh1-6178-corr.2011
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00448.2010
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajpendo.00448.2010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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