NQO1 protects obese mice through improvements in glucose and lipid metabolism

Abstract Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Andrea Di Francesco, Youngshim Choi, Michel Bernier, Yingchun Zhang, Alberto Diaz-Ruiz, Miguel A. Aon, Krystle Kalafut, Margaux R. Ehrlich, Kelsey Murt, Ahmed Ali, Kevin J. Pearson, Sophie Levan, Joshua D. Preston, Alejandro Martin-Montalvo, Jennifer L. Martindale, Kotb Abdelmohsen, Cole R. Michel, Diana M. Willmes, Christine Henke, Placido Navas, Jose Manuel Villalba, David Siegel, Myriam Gorospe, Kristofer Fritz, Shyam Biswal, David Ross, Rafael de Cabo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/fcd69445e0874cb1841372862929c6f9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fcd69445e0874cb1841372862929c6f9
record_format	dspace
spelling	oai:doaj.org-article:fcd69445e0874cb1841372862929c6f92021-12-02T14:18:30ZNQO1 protects obese mice through improvements in glucose and lipid metabolism10.1038/s41514-020-00051-62056-3973https://doaj.org/article/fcd69445e0874cb1841372862929c6f92020-11-01T00:00:00Zhttps://doi.org/10.1038/s41514-020-00051-6https://doaj.org/toc/2056-3973Abstract Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD+ metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.Andrea Di FrancescoYoungshim ChoiMichel BernierYingchun ZhangAlberto Diaz-RuizMiguel A. AonKrystle KalafutMargaux R. EhrlichKelsey MurtAhmed AliKevin J. PearsonSophie LevanJoshua D. PrestonAlejandro Martin-MontalvoJennifer L. MartindaleKotb AbdelmohsenCole R. MichelDiana M. WillmesChristine HenkePlacido NavasJose Manuel VillalbaDavid SiegelMyriam GorospeKristofer FritzShyam BiswalDavid RossRafael de CaboNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 6, Iss 1, Pp 1-18 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Andrea Di Francesco Youngshim Choi Michel Bernier Yingchun Zhang Alberto Diaz-Ruiz Miguel A. Aon Krystle Kalafut Margaux R. Ehrlich Kelsey Murt Ahmed Ali Kevin J. Pearson Sophie Levan Joshua D. Preston Alejandro Martin-Montalvo Jennifer L. Martindale Kotb Abdelmohsen Cole R. Michel Diana M. Willmes Christine Henke Placido Navas Jose Manuel Villalba David Siegel Myriam Gorospe Kristofer Fritz Shyam Biswal David Ross Rafael de Cabo NQO1 protects obese mice through improvements in glucose and lipid metabolism
description	Abstract Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD+ metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.
format	article
author	Andrea Di Francesco Youngshim Choi Michel Bernier Yingchun Zhang Alberto Diaz-Ruiz Miguel A. Aon Krystle Kalafut Margaux R. Ehrlich Kelsey Murt Ahmed Ali Kevin J. Pearson Sophie Levan Joshua D. Preston Alejandro Martin-Montalvo Jennifer L. Martindale Kotb Abdelmohsen Cole R. Michel Diana M. Willmes Christine Henke Placido Navas Jose Manuel Villalba David Siegel Myriam Gorospe Kristofer Fritz Shyam Biswal David Ross Rafael de Cabo
author_facet	Andrea Di Francesco Youngshim Choi Michel Bernier Yingchun Zhang Alberto Diaz-Ruiz Miguel A. Aon Krystle Kalafut Margaux R. Ehrlich Kelsey Murt Ahmed Ali Kevin J. Pearson Sophie Levan Joshua D. Preston Alejandro Martin-Montalvo Jennifer L. Martindale Kotb Abdelmohsen Cole R. Michel Diana M. Willmes Christine Henke Placido Navas Jose Manuel Villalba David Siegel Myriam Gorospe Kristofer Fritz Shyam Biswal David Ross Rafael de Cabo
author_sort	Andrea Di Francesco
title	NQO1 protects obese mice through improvements in glucose and lipid metabolism
title_short	NQO1 protects obese mice through improvements in glucose and lipid metabolism
title_full	NQO1 protects obese mice through improvements in glucose and lipid metabolism
title_fullStr	NQO1 protects obese mice through improvements in glucose and lipid metabolism
title_full_unstemmed	NQO1 protects obese mice through improvements in glucose and lipid metabolism
title_sort	nqo1 protects obese mice through improvements in glucose and lipid metabolism
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/fcd69445e0874cb1841372862929c6f9
work_keys_str_mv	AT andreadifrancesco nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT youngshimchoi nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT michelbernier nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT yingchunzhang nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT albertodiazruiz nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT miguelaaon nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT krystlekalafut nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT margauxrehrlich nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT kelseymurt nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT ahmedali nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT kevinjpearson nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT sophielevan nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT joshuadpreston nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT alejandromartinmontalvo nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT jenniferlmartindale nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT kotbabdelmohsen nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT colermichel nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT dianamwillmes nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT christinehenke nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT placidonavas nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT josemanuelvillalba nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT davidsiegel nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT myriamgorospe nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT kristoferfritz nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT shyambiswal nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT davidross nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism AT rafaeldecabo nqo1protectsobesemicethroughimprovementsinglucoseandlipidmetabolism
_version_	1718391643228340224

NQO1 protects obese mice through improvements in glucose and lipid metabolism

Ejemplares similares