Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action

Autores
Pagnotta, Priscila Ayelén; Gantov, Mariana; Fletcher, Sabrina Johanna; Lombardi, Antonella; Crosbie, María Lujan; Santiso, Natalia; Ursino, Anabela; Frascarolli, Celeste; Amato, Alicia; Dreszman, Rubén; Calvo, Juan Carlos; Toneatto, Judith
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in cancer associated adipocytes (CAA). However, the paracrine effects of CAA on lipid metabolism and microenvironment remodeling remain poorly understood. Methods: To analyze these changes, we evaluated the effects of factors in conditioned media (CM) derived from explants of human breast adipose tissue from tumor (hATT) or normal (hATN) on morphology, degree of browning, the levels of adiposity, maturity, and lipolytic-related markers in 3T3-L1 white adipocytes by Western blot, indirect immunofluorescence and lipolytic assay. We analyzed subcellular localization of UCP1, perilipin 1 (Plin1), HSL and ATGL in adipocytes incubated with different CM by indirect immunofluorescence. Additionally, we evaluated changes in adipocyte intracellular signal pathways. Results: We found that adipocytes incubated with hATT-CM displayed characteristics that morphologically resembled beige/brown adipocytes with smaller cell size and higher number of small and micro lipid droplets (LDs), with less triglyceride content. Both, hATT-CM and hATN-CM, increased Pref-1, C/EBPβ LIP/LAP ratio, PPARγ, and caveolin 1 expression in white adipocytes. UCP1, PGC1α and TOMM20 increased only in adipocytes that were treated with hATT-CM. Also, hATT-CM increased the levels of Plin1 and HSL, while decreased ATGL. hATT-CM modified the subcellular localization of the lipolytic markers, favoring their relative content around micro-LDs and induced Plin1 segregation. Furthermore, the levels of p-HSL, p-ERK and p-AKT increased in white adipocytes after incubation with hATT-CM. Conclusions: In summary, these findings allow us to conclude that adipocytes attached to the tumor could induce white adipocyte browning and increase lipolysis as a means for endocrine/paracrine signaling. Thus, adipocytes from the tumor microenvironment exhibit an activated phenotype that could have been induced not only by secreted soluble factors from tumor cells but also by paracrine action from other adipocytes present in this microenvironment, suggesting a “domino effect”.
Fil: Pagnotta, Priscila Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Gantov, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Fletcher, Sabrina Johanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lombardi, Antonella. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Crosbie, María Lujan. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Santiso, Natalia. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Ursino, Anabela. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Frascarolli, Celeste. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Amato, Alicia. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Dreszman, Rubén. No especifíca;
Fil: Calvo, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
BROWNING
HUMAN BREAST ADIPOSE TISSUE
LIPOLYSIS
PARACRINE ACTION
TUMOR MICROENVIRONMENT
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:11336/216142
Acceder
id CONICETDig_9fd0f14172b9360a9622ba6ecc419ad5
oai_identifier_str oai:ri.conicet.gov.ar:11336/216142
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine actionPagnotta, Priscila AyelénGantov, MarianaFletcher, Sabrina JohannaLombardi, AntonellaCrosbie, María LujanSantiso, NataliaUrsino, AnabelaFrascarolli, CelesteAmato, AliciaDreszman, RubénCalvo, Juan CarlosToneatto, JudithBROWNINGHUMAN BREAST ADIPOSE TISSUELIPOLYSISPARACRINE ACTIONTUMOR MICROENVIRONMENThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in cancer associated adipocytes (CAA). However, the paracrine effects of CAA on lipid metabolism and microenvironment remodeling remain poorly understood. Methods: To analyze these changes, we evaluated the effects of factors in conditioned media (CM) derived from explants of human breast adipose tissue from tumor (hATT) or normal (hATN) on morphology, degree of browning, the levels of adiposity, maturity, and lipolytic-related markers in 3T3-L1 white adipocytes by Western blot, indirect immunofluorescence and lipolytic assay. We analyzed subcellular localization of UCP1, perilipin 1 (Plin1), HSL and ATGL in adipocytes incubated with different CM by indirect immunofluorescence. Additionally, we evaluated changes in adipocyte intracellular signal pathways. Results: We found that adipocytes incubated with hATT-CM displayed characteristics that morphologically resembled beige/brown adipocytes with smaller cell size and higher number of small and micro lipid droplets (LDs), with less triglyceride content. Both, hATT-CM and hATN-CM, increased Pref-1, C/EBPβ LIP/LAP ratio, PPARγ, and caveolin 1 expression in white adipocytes. UCP1, PGC1α and TOMM20 increased only in adipocytes that were treated with hATT-CM. Also, hATT-CM increased the levels of Plin1 and HSL, while decreased ATGL. hATT-CM modified the subcellular localization of the lipolytic markers, favoring their relative content around micro-LDs and induced Plin1 segregation. Furthermore, the levels of p-HSL, p-ERK and p-AKT increased in white adipocytes after incubation with hATT-CM. Conclusions: In summary, these findings allow us to conclude that adipocytes attached to the tumor could induce white adipocyte browning and increase lipolysis as a means for endocrine/paracrine signaling. Thus, adipocytes from the tumor microenvironment exhibit an activated phenotype that could have been induced not only by secreted soluble factors from tumor cells but also by paracrine action from other adipocytes present in this microenvironment, suggesting a “domino effect”.Fil: Pagnotta, Priscila Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gantov, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fletcher, Sabrina Johanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lombardi, Antonella. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Crosbie, María Lujan. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Santiso, Natalia. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Ursino, Anabela. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Frascarolli, Celeste. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Amato, Alicia. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Dreszman, Rubén. No especifíca;Fil: Calvo, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFrontiers Media2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216142Pagnotta, Priscila Ayelén; Gantov, Mariana; Fletcher, Sabrina Johanna; Lombardi, Antonella; Crosbie, María Lujan; et al.; Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action; Frontiers Media; Frontiers in Endocrinology; 14; 4-2023; 1-171664-2392CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2023.1144016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:28Zoai:ri.conicet.gov.ar:11336/216142instacron: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 10:08:29.011CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
title Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
spellingShingle Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
Pagnotta, Priscila Ayelén
BROWNING
HUMAN BREAST ADIPOSE TISSUE
LIPOLYSIS
PARACRINE ACTION
TUMOR MICROENVIRONMENT
title_short Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
title_full Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
title_fullStr Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
title_full_unstemmed Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
title_sort Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action
dc.creator.none.fl_str_mv Pagnotta, Priscila Ayelén
Gantov, Mariana
Fletcher, Sabrina Johanna
Lombardi, Antonella
Crosbie, María Lujan
Santiso, Natalia
Ursino, Anabela
Frascarolli, Celeste
Amato, Alicia
Dreszman, Rubén
Calvo, Juan Carlos
Toneatto, Judith
author Pagnotta, Priscila Ayelén
author_facet Pagnotta, Priscila Ayelén
Gantov, Mariana
Fletcher, Sabrina Johanna
Lombardi, Antonella
Crosbie, María Lujan
Santiso, Natalia
Ursino, Anabela
Frascarolli, Celeste
Amato, Alicia
Dreszman, Rubén
Calvo, Juan Carlos
Toneatto, Judith
author_role author
author2 Gantov, Mariana
Fletcher, Sabrina Johanna
Lombardi, Antonella
Crosbie, María Lujan
Santiso, Natalia
Ursino, Anabela
Frascarolli, Celeste
Amato, Alicia
Dreszman, Rubén
Calvo, Juan Carlos
Toneatto, Judith
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BROWNING
HUMAN BREAST ADIPOSE TISSUE
LIPOLYSIS
PARACRINE ACTION
TUMOR MICROENVIRONMENT
topic BROWNING
HUMAN BREAST ADIPOSE TISSUE
LIPOLYSIS
PARACRINE ACTION
TUMOR MICROENVIRONMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in cancer associated adipocytes (CAA). However, the paracrine effects of CAA on lipid metabolism and microenvironment remodeling remain poorly understood. Methods: To analyze these changes, we evaluated the effects of factors in conditioned media (CM) derived from explants of human breast adipose tissue from tumor (hATT) or normal (hATN) on morphology, degree of browning, the levels of adiposity, maturity, and lipolytic-related markers in 3T3-L1 white adipocytes by Western blot, indirect immunofluorescence and lipolytic assay. We analyzed subcellular localization of UCP1, perilipin 1 (Plin1), HSL and ATGL in adipocytes incubated with different CM by indirect immunofluorescence. Additionally, we evaluated changes in adipocyte intracellular signal pathways. Results: We found that adipocytes incubated with hATT-CM displayed characteristics that morphologically resembled beige/brown adipocytes with smaller cell size and higher number of small and micro lipid droplets (LDs), with less triglyceride content. Both, hATT-CM and hATN-CM, increased Pref-1, C/EBPβ LIP/LAP ratio, PPARγ, and caveolin 1 expression in white adipocytes. UCP1, PGC1α and TOMM20 increased only in adipocytes that were treated with hATT-CM. Also, hATT-CM increased the levels of Plin1 and HSL, while decreased ATGL. hATT-CM modified the subcellular localization of the lipolytic markers, favoring their relative content around micro-LDs and induced Plin1 segregation. Furthermore, the levels of p-HSL, p-ERK and p-AKT increased in white adipocytes after incubation with hATT-CM. Conclusions: In summary, these findings allow us to conclude that adipocytes attached to the tumor could induce white adipocyte browning and increase lipolysis as a means for endocrine/paracrine signaling. Thus, adipocytes from the tumor microenvironment exhibit an activated phenotype that could have been induced not only by secreted soluble factors from tumor cells but also by paracrine action from other adipocytes present in this microenvironment, suggesting a “domino effect”.
Fil: Pagnotta, Priscila Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Gantov, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Fletcher, Sabrina Johanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lombardi, Antonella. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Crosbie, María Lujan. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Santiso, Natalia. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Ursino, Anabela. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Frascarolli, Celeste. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Amato, Alicia. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina
Fil: Dreszman, Rubén. No especifíca;
Fil: Calvo, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Background: Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in cancer associated adipocytes (CAA). However, the paracrine effects of CAA on lipid metabolism and microenvironment remodeling remain poorly understood. Methods: To analyze these changes, we evaluated the effects of factors in conditioned media (CM) derived from explants of human breast adipose tissue from tumor (hATT) or normal (hATN) on morphology, degree of browning, the levels of adiposity, maturity, and lipolytic-related markers in 3T3-L1 white adipocytes by Western blot, indirect immunofluorescence and lipolytic assay. We analyzed subcellular localization of UCP1, perilipin 1 (Plin1), HSL and ATGL in adipocytes incubated with different CM by indirect immunofluorescence. Additionally, we evaluated changes in adipocyte intracellular signal pathways. Results: We found that adipocytes incubated with hATT-CM displayed characteristics that morphologically resembled beige/brown adipocytes with smaller cell size and higher number of small and micro lipid droplets (LDs), with less triglyceride content. Both, hATT-CM and hATN-CM, increased Pref-1, C/EBPβ LIP/LAP ratio, PPARγ, and caveolin 1 expression in white adipocytes. UCP1, PGC1α and TOMM20 increased only in adipocytes that were treated with hATT-CM. Also, hATT-CM increased the levels of Plin1 and HSL, while decreased ATGL. hATT-CM modified the subcellular localization of the lipolytic markers, favoring their relative content around micro-LDs and induced Plin1 segregation. Furthermore, the levels of p-HSL, p-ERK and p-AKT increased in white adipocytes after incubation with hATT-CM. Conclusions: In summary, these findings allow us to conclude that adipocytes attached to the tumor could induce white adipocyte browning and increase lipolysis as a means for endocrine/paracrine signaling. Thus, adipocytes from the tumor microenvironment exhibit an activated phenotype that could have been induced not only by secreted soluble factors from tumor cells but also by paracrine action from other adipocytes present in this microenvironment, suggesting a “domino effect”.
publishDate 2023
dc.date.none.fl_str_mv 2023-04
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/11336/216142
Pagnotta, Priscila Ayelén; Gantov, Mariana; Fletcher, Sabrina Johanna; Lombardi, Antonella; Crosbie, María Lujan; et al.; Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action; Frontiers Media; Frontiers in Endocrinology; 14; 4-2023; 1-17
1664-2392
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216142
identifier_str_mv Pagnotta, Priscila Ayelén; Gantov, Mariana; Fletcher, Sabrina Johanna; Lombardi, Antonella; Crosbie, María Lujan; et al.; Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action; Frontiers Media; Frontiers in Endocrinology; 14; 4-2023; 1-17
1664-2392
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2023.1144016
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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