Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior

Abstract Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regu...

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Autores principales:	Romina María Uranga, Carola Millán, María José Barahona, Antonia Recabal, Magdiel Salgado, Fernando Martinez, Patricio Ordenes, Roberto Elizondo-Vega, Fernando Sepúlveda, Elena Uribe, María de los Ángeles García-Robles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/462393bf23864745b7aa4f27a3d1fc85
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spelling	oai:doaj.org-article:462393bf23864745b7aa4f27a3d1fc852021-12-02T15:05:09ZAdenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior10.1038/s41598-017-03928-x2045-2322https://doaj.org/article/462393bf23864745b7aa4f27a3d1fc852017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03928-xhttps://doaj.org/toc/2045-2322Abstract Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons. In this study, we developed an adenovirus expressing GK shRNA to inhibit GK expression in vivo. When injected into the 3V of rats, this adenovirus preferentially transduced tanycytes. qRT-PCR and Western blot assays confirmed GK mRNA and protein levels were lower in GK knockdown animals compared to the controls. In response to an intracerebroventricular glucose injection, the mRNA levels of anorexigenic POMC and CART and orexigenic AgRP and NPY neuropeptides were altered in GK knockdown animals. Similarly, food intake, meal duration, frequency of eating events and the cumulative eating time were increased, whereas the intervals between meals were decreased in GK knockdown rats, suggesting a decrease in satiety. Thus, GK expression in the ventricular cells appears to play an important role in feeding behavior.Romina María UrangaCarola MillánMaría José BarahonaAntonia RecabalMagdiel SalgadoFernando MartinezPatricio OrdenesRoberto Elizondo-VegaFernando SepúlvedaElena UribeMaría de los Ángeles García-RoblesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Romina María Uranga Carola Millán María José Barahona Antonia Recabal Magdiel Salgado Fernando Martinez Patricio Ordenes Roberto Elizondo-Vega Fernando Sepúlveda Elena Uribe María de los Ángeles García-Robles Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
description	Abstract Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons. In this study, we developed an adenovirus expressing GK shRNA to inhibit GK expression in vivo. When injected into the 3V of rats, this adenovirus preferentially transduced tanycytes. qRT-PCR and Western blot assays confirmed GK mRNA and protein levels were lower in GK knockdown animals compared to the controls. In response to an intracerebroventricular glucose injection, the mRNA levels of anorexigenic POMC and CART and orexigenic AgRP and NPY neuropeptides were altered in GK knockdown animals. Similarly, food intake, meal duration, frequency of eating events and the cumulative eating time were increased, whereas the intervals between meals were decreased in GK knockdown rats, suggesting a decrease in satiety. Thus, GK expression in the ventricular cells appears to play an important role in feeding behavior.
format	article
author	Romina María Uranga Carola Millán María José Barahona Antonia Recabal Magdiel Salgado Fernando Martinez Patricio Ordenes Roberto Elizondo-Vega Fernando Sepúlveda Elena Uribe María de los Ángeles García-Robles
author_facet	Romina María Uranga Carola Millán María José Barahona Antonia Recabal Magdiel Salgado Fernando Martinez Patricio Ordenes Roberto Elizondo-Vega Fernando Sepúlveda Elena Uribe María de los Ángeles García-Robles
author_sort	Romina María Uranga
title	Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
title_short	Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
title_full	Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
title_fullStr	Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
title_full_unstemmed	Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
title_sort	adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/462393bf23864745b7aa4f27a3d1fc85
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Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior

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