The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development

Autores
Hsiao, Wen Yu; Jung, Su Myung; Tang, Yuefeng; Haley, John A.; Li, Rui; Li, Huawei; Martinez Calejman, Camila; Sanchez Gurmaches, Joan; Hung, Chien-Min; Luciano, Amelia K.; DeMambro, Victoria; Wellen, Kathryn E.; Rosen, Clifford J.; Zhu, Lihua Julie; Guertin, David A.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.
Fil: Hsiao, Wen Yu. University Of Massachussets. Medical School; Estados Unidos
Fil: Jung, Su Myung. University Of Massachussets. Medical School; Estados Unidos
Fil: Tang, Yuefeng. University Of Massachussets. Medical School; Estados Unidos
Fil: Haley, John A.. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Rui. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Huawei. University Of Massachussets. Medical School; Estados Unidos
Fil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. University Of Massachussets. Medical School; Estados Unidos
Fil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados Unidos. University of Cincinnati; Estados Unidos
Fil: Hung, Chien-Min. University Of Massachussets. Medical School; Estados Unidos
Fil: Luciano, Amelia K.. University Of Massachussets. Medical School; Estados Unidos
Fil: DeMambro, Victoria. University of Maine; Estados Unidos
Fil: Wellen, Kathryn E.. University of Pennsylvania; Estados Unidos
Fil: Rosen, Clifford J.. University of Maine; Estados Unidos
Fil: Zhu, Lihua Julie. University Of Massachussets. Medical School; Estados Unidos
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos
Materia
ADIPOCYTE
ADIPOSE TISSUE
AKT
CHREBP
LIPID METABOLISM
MTORC2
OBESITY
PPAR-GAMMA
TYPE 2 DIABETES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182661
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during DevelopmentHsiao, Wen YuJung, Su MyungTang, YuefengHaley, John A.Li, RuiLi, HuaweiMartinez Calejman, CamilaSanchez Gurmaches, JoanHung, Chien-MinLuciano, Amelia K.DeMambro, VictoriaWellen, Kathryn E.Rosen, Clifford J.Zhu, Lihua JulieGuertin, David A.ADIPOCYTEADIPOSE TISSUEAKTCHREBPLIPID METABOLISMMTORC2OBESITYPPAR-GAMMATYPE 2 DIABETEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.Fil: Hsiao, Wen Yu. University Of Massachussets. Medical School; Estados UnidosFil: Jung, Su Myung. University Of Massachussets. Medical School; Estados UnidosFil: Tang, Yuefeng. University Of Massachussets. Medical School; Estados UnidosFil: Haley, John A.. University Of Massachussets. Medical School; Estados UnidosFil: Li, Rui. University Of Massachussets. Medical School; Estados UnidosFil: Li, Huawei. University Of Massachussets. Medical School; Estados UnidosFil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. University Of Massachussets. Medical School; Estados UnidosFil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados Unidos. University of Cincinnati; Estados UnidosFil: Hung, Chien-Min. University Of Massachussets. Medical School; Estados UnidosFil: Luciano, Amelia K.. University Of Massachussets. Medical School; Estados UnidosFil: DeMambro, Victoria. University of Maine; Estados UnidosFil: Wellen, Kathryn E.. University of Pennsylvania; Estados UnidosFil: Rosen, Clifford J.. University of Maine; Estados UnidosFil: Zhu, Lihua Julie. University Of Massachussets. Medical School; Estados UnidosFil: Guertin, David A.. University Of Massachussets. Medical School; Estados UnidosElsevier Science2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182661Hsiao, Wen Yu; Jung, Su Myung; Tang, Yuefeng; Haley, John A.; Li, Rui; et al.; The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development; Elsevier Science; Cell Reports; 33; 1; 10-2020; 1-252211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124720312122info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.108223info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:06Zoai:ri.conicet.gov.ar:11336/182661instacron: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 09:45:06.578CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
title The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
spellingShingle The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
Hsiao, Wen Yu
ADIPOCYTE
ADIPOSE TISSUE
AKT
CHREBP
LIPID METABOLISM
MTORC2
OBESITY
PPAR-GAMMA
TYPE 2 DIABETES
title_short The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
title_full The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
title_fullStr The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
title_full_unstemmed The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
title_sort The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
dc.creator.none.fl_str_mv Hsiao, Wen Yu
Jung, Su Myung
Tang, Yuefeng
Haley, John A.
Li, Rui
Li, Huawei
Martinez Calejman, Camila
Sanchez Gurmaches, Joan
Hung, Chien-Min
Luciano, Amelia K.
DeMambro, Victoria
Wellen, Kathryn E.
Rosen, Clifford J.
Zhu, Lihua Julie
Guertin, David A.
author Hsiao, Wen Yu
author_facet Hsiao, Wen Yu
Jung, Su Myung
Tang, Yuefeng
Haley, John A.
Li, Rui
Li, Huawei
Martinez Calejman, Camila
Sanchez Gurmaches, Joan
Hung, Chien-Min
Luciano, Amelia K.
DeMambro, Victoria
Wellen, Kathryn E.
Rosen, Clifford J.
Zhu, Lihua Julie
Guertin, David A.
author_role author
author2 Jung, Su Myung
Tang, Yuefeng
Haley, John A.
Li, Rui
Li, Huawei
Martinez Calejman, Camila
Sanchez Gurmaches, Joan
Hung, Chien-Min
Luciano, Amelia K.
DeMambro, Victoria
Wellen, Kathryn E.
Rosen, Clifford J.
Zhu, Lihua Julie
Guertin, David A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADIPOCYTE
ADIPOSE TISSUE
AKT
CHREBP
LIPID METABOLISM
MTORC2
OBESITY
PPAR-GAMMA
TYPE 2 DIABETES
topic ADIPOCYTE
ADIPOSE TISSUE
AKT
CHREBP
LIPID METABOLISM
MTORC2
OBESITY
PPAR-GAMMA
TYPE 2 DIABETES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.
Fil: Hsiao, Wen Yu. University Of Massachussets. Medical School; Estados Unidos
Fil: Jung, Su Myung. University Of Massachussets. Medical School; Estados Unidos
Fil: Tang, Yuefeng. University Of Massachussets. Medical School; Estados Unidos
Fil: Haley, John A.. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Rui. University Of Massachussets. Medical School; Estados Unidos
Fil: Li, Huawei. University Of Massachussets. Medical School; Estados Unidos
Fil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. University Of Massachussets. Medical School; Estados Unidos
Fil: Sanchez Gurmaches, Joan. University Of Massachussets. Medical School; Estados Unidos. University of Cincinnati; Estados Unidos
Fil: Hung, Chien-Min. University Of Massachussets. Medical School; Estados Unidos
Fil: Luciano, Amelia K.. University Of Massachussets. Medical School; Estados Unidos
Fil: DeMambro, Victoria. University of Maine; Estados Unidos
Fil: Wellen, Kathryn E.. University of Pennsylvania; Estados Unidos
Fil: Rosen, Clifford J.. University of Maine; Estados Unidos
Fil: Zhu, Lihua Julie. University Of Massachussets. Medical School; Estados Unidos
Fil: Guertin, David A.. University Of Massachussets. Medical School; Estados Unidos
description Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
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/11336/182661
Hsiao, Wen Yu; Jung, Su Myung; Tang, Yuefeng; Haley, John A.; Li, Rui; et al.; The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development; Elsevier Science; Cell Reports; 33; 1; 10-2020; 1-25
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182661
identifier_str_mv Hsiao, Wen Yu; Jung, Su Myung; Tang, Yuefeng; Haley, John A.; Li, Rui; et al.; The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development; Elsevier Science; Cell Reports; 33; 1; 10-2020; 1-25
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124720312122
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.108223
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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
_version_ 1842268709811388416
score 13.13397

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