Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis

Autores
Sanchez Gurmaches, Joan; Tang, Yuefeng; Jespersen, Naja Zenius; Wallace, Martina; Martinez Calejman, Camila; Gujja, Sharvari; Li, Huawei; Edwards, Yvonne J.K.; Metallo, Christian M.; Nielsen, Søren; Scheele, Camilla; Guertin, David A.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis. Sanchez-Gurmaches et al. reveal a mechanism by which AKT signaling and metabolism intersect through ChREBP in brown fat to simultaneously promote lipid synthesis and oxidation, a paradoxical and poorly understood feature of thermogenesis. This pathway is required for optimum brown fat function and conserved in humans.
Fil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados Unidos
Fil: Tang, Yuefeng. University Of Massachussets. Medical School; Estados Unidos
Fil: Jespersen, Naja Zenius. Universidad de Copenhagen; Dinamarca
Fil: Wallace, Martina. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences.; Estados Unidos
Fil: Martinez Calejman, Camila. University Of Massachussets. Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gujja, Sharvari. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Huawei. University Of Massachussets. Medical School; Estados Unidos
Fil: Edwards, Yvonne J.K.. University Of Massachussets. Medical School; Estados Unidos
Fil: Metallo, Christian M.. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences.; Estados Unidos
Fil: Nielsen, Søren. Universidad de Copenhagen; Dinamarca
Fil: Scheele, Camilla. Universidad de Copenhagen; Dinamarca
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos
Materia
AKT
INSULIN SIGNALLING
LIPID METABOLISM
LIPID SYNTHESIS
OBESITY
SREBP
THERMOGENESIS
UCP1
WHITE FAT
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:11336/167077
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/167077
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and ThermogenesisSanchez Gurmaches, JoanTang, YuefengJespersen, Naja ZeniusWallace, MartinaMartinez Calejman, CamilaGujja, SharvariLi, HuaweiEdwards, Yvonne J.K.Metallo, Christian M.Nielsen, SørenScheele, CamillaGuertin, David A.AKTINSULIN SIGNALLINGLIPID METABOLISMLIPID SYNTHESISOBESITYSREBPTHERMOGENESISUCP1WHITE FAThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis. Sanchez-Gurmaches et al. reveal a mechanism by which AKT signaling and metabolism intersect through ChREBP in brown fat to simultaneously promote lipid synthesis and oxidation, a paradoxical and poorly understood feature of thermogenesis. This pathway is required for optimum brown fat function and conserved in humans.Fil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados UnidosFil: Tang, Yuefeng. University Of Massachussets. Medical School; Estados UnidosFil: Jespersen, Naja Zenius. Universidad de Copenhagen; DinamarcaFil: Wallace, Martina. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences.; Estados UnidosFil: Martinez Calejman, Camila. University Of Massachussets. Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gujja, Sharvari. University Of Massachussets. Medical School; Estados UnidosFil: Li, Huawei. University Of Massachussets. Medical School; Estados UnidosFil: Edwards, Yvonne J.K.. University Of Massachussets. Medical School; Estados UnidosFil: Metallo, Christian M.. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences.; Estados UnidosFil: Nielsen, Søren. Universidad de Copenhagen; DinamarcaFil: Scheele, Camilla. Universidad de Copenhagen; DinamarcaFil: Guertin, David A.. University Of Massachussets. Medical School; Estados UnidosCell Press2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/167077Sanchez Gurmaches, Joan; Tang, Yuefeng; Jespersen, Naja Zenius; Wallace, Martina; Martinez Calejman, Camila; et al.; Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis; Cell Press; Cell Metabolism; 27; 1; 1-2018; 195-209.e61550-4131CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S1550413117306204info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2017.10.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:04:08Zoai:ri.conicet.gov.ar:11336/167077instacron: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:34982025-09-29 10:04:08.808CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
title Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
spellingShingle Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
Sanchez Gurmaches, Joan
AKT
INSULIN SIGNALLING
LIPID METABOLISM
LIPID SYNTHESIS
OBESITY
SREBP
THERMOGENESIS
UCP1
WHITE FAT
title_short Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
title_full Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
title_fullStr Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
title_full_unstemmed Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
title_sort Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
dc.creator.none.fl_str_mv Sanchez Gurmaches, Joan
Tang, Yuefeng
Jespersen, Naja Zenius
Wallace, Martina
Martinez Calejman, Camila
Gujja, Sharvari
Li, Huawei
Edwards, Yvonne J.K.
Metallo, Christian M.
Nielsen, Søren
Scheele, Camilla
Guertin, David A.
author Sanchez Gurmaches, Joan
author_facet Sanchez Gurmaches, Joan
Tang, Yuefeng
Jespersen, Naja Zenius
Wallace, Martina
Martinez Calejman, Camila
Gujja, Sharvari
Li, Huawei
Edwards, Yvonne J.K.
Metallo, Christian M.
Nielsen, Søren
Scheele, Camilla
Guertin, David A.
author_role author
author2 Tang, Yuefeng
Jespersen, Naja Zenius
Wallace, Martina
Martinez Calejman, Camila
Gujja, Sharvari
Li, Huawei
Edwards, Yvonne J.K.
Metallo, Christian M.
Nielsen, Søren
Scheele, Camilla
Guertin, David A.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AKT
INSULIN SIGNALLING
LIPID METABOLISM
LIPID SYNTHESIS
OBESITY
SREBP
THERMOGENESIS
UCP1
WHITE FAT
topic AKT
INSULIN SIGNALLING
LIPID METABOLISM
LIPID SYNTHESIS
OBESITY
SREBP
THERMOGENESIS
UCP1
WHITE FAT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis. Sanchez-Gurmaches et al. reveal a mechanism by which AKT signaling and metabolism intersect through ChREBP in brown fat to simultaneously promote lipid synthesis and oxidation, a paradoxical and poorly understood feature of thermogenesis. This pathway is required for optimum brown fat function and conserved in humans.
Fil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados Unidos
Fil: Tang, Yuefeng. University Of Massachussets. Medical School; Estados Unidos
Fil: Jespersen, Naja Zenius. Universidad de Copenhagen; Dinamarca
Fil: Wallace, Martina. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences.; Estados Unidos
Fil: Martinez Calejman, Camila. University Of Massachussets. Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gujja, Sharvari. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Huawei. University Of Massachussets. Medical School; Estados Unidos
Fil: Edwards, Yvonne J.K.. University Of Massachussets. Medical School; Estados Unidos
Fil: Metallo, Christian M.. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences.; Estados Unidos
Fil: Nielsen, Søren. Universidad de Copenhagen; Dinamarca
Fil: Scheele, Camilla. Universidad de Copenhagen; Dinamarca
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos
description Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis. Sanchez-Gurmaches et al. reveal a mechanism by which AKT signaling and metabolism intersect through ChREBP in brown fat to simultaneously promote lipid synthesis and oxidation, a paradoxical and poorly understood feature of thermogenesis. This pathway is required for optimum brown fat function and conserved in humans.
publishDate 2018
dc.date.none.fl_str_mv 2018-01
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/11336/167077
Sanchez Gurmaches, Joan; Tang, Yuefeng; Jespersen, Naja Zenius; Wallace, Martina; Martinez Calejman, Camila; et al.; Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis; Cell Press; Cell Metabolism; 27; 1; 1-2018; 195-209.e6
1550-4131
CONICET Digital
CONICET
url http://hdl.handle.net/11336/167077
identifier_str_mv Sanchez Gurmaches, Joan; Tang, Yuefeng; Jespersen, Naja Zenius; Wallace, Martina; Martinez Calejman, Camila; et al.; Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis; Cell Press; Cell Metabolism; 27; 1; 1-2018; 195-209.e6
1550-4131
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S1550413117306204
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2017.10.008
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 Cell Press
publisher.none.fl_str_mv Cell Press
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 13.070432

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