Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets

Autores
Hinojosa Vera, Kathleen Fabiola; Hema Kumar, C.; Bilachi, R.S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Obesity-associated metabolic dysfunction is closely linked to chronic low-grade inflammation, or metaflammation, which is predominantly driven by changes in AT homeostasis. Macrophages, key components of the innate immune system, are central regulators of this inflammatory process. In lean AT, resident macrophages (AT-associated macrophages [ATMs]) exhibit an anti-inflammatory phenotype and support tissue homeostasis. However, during obesity, AT undergoes hypoxia, mechanical stress, and lipid overload, leading to immune cell infiltration and a phenotypic switch of ATMs toward a proinflammatory M1 profile. This shift contributes to systemic inflammation and obesity-associated metabolic risks. Here, we review the current understanding of macrophage polarization in obesity, highlighting the transcriptomic plasticity and functional heterogeneity of ATMs, their interactions within the AT microenvironment, and the formation of crown-like structures (CLSs) as a structural hallmark of AT inflammation. We also discuss the regulatory functions of transcription factors, such as hypoxia-inducible factor (HIF) 1α (HIF-1α) and peroxisome proliferator activated receptor gamma (PPARγ), that control the phenotypic switch of macrophages in healthy and obese ATs. Furthermore, we examined emerging macrophage subsets, such as CD9+ and Trem2+ lipid-associated macrophages (LAMs), and their dual roles in AT remodeling and inflammation. Understanding the complex network of macrophage activation in obese AT is essential for identifying therapeutic targets aimed at mitigating obesity-associated metabolic risk and restoring tissue function.
Fil: Hinojosa Vera, Kathleen Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Hema Kumar, C.. Dayananda Sagar College of Engineering; India
Fil: Bilachi, R.S.. Manipal Institute Of Technology; India
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
OBESITY
ADIPOSE MACROPHAGE
GENE EXPRESSION
PHENOTYPIC SWITCH
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/290283
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and TargetsHinojosa Vera, Kathleen FabiolaHema Kumar, C.Bilachi, R.S.Ramirez, DarioGomez Mejiba, Sandra EstherOBESITYADIPOSE MACROPHAGEGENE EXPRESSIONPHENOTYPIC SWITCHhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Obesity-associated metabolic dysfunction is closely linked to chronic low-grade inflammation, or metaflammation, which is predominantly driven by changes in AT homeostasis. Macrophages, key components of the innate immune system, are central regulators of this inflammatory process. In lean AT, resident macrophages (AT-associated macrophages [ATMs]) exhibit an anti-inflammatory phenotype and support tissue homeostasis. However, during obesity, AT undergoes hypoxia, mechanical stress, and lipid overload, leading to immune cell infiltration and a phenotypic switch of ATMs toward a proinflammatory M1 profile. This shift contributes to systemic inflammation and obesity-associated metabolic risks. Here, we review the current understanding of macrophage polarization in obesity, highlighting the transcriptomic plasticity and functional heterogeneity of ATMs, their interactions within the AT microenvironment, and the formation of crown-like structures (CLSs) as a structural hallmark of AT inflammation. We also discuss the regulatory functions of transcription factors, such as hypoxia-inducible factor (HIF) 1α (HIF-1α) and peroxisome proliferator activated receptor gamma (PPARγ), that control the phenotypic switch of macrophages in healthy and obese ATs. Furthermore, we examined emerging macrophage subsets, such as CD9+ and Trem2+ lipid-associated macrophages (LAMs), and their dual roles in AT remodeling and inflammation. Understanding the complex network of macrophage activation in obese AT is essential for identifying therapeutic targets aimed at mitigating obesity-associated metabolic risk and restoring tissue function.Fil: Hinojosa Vera, Kathleen Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Hema Kumar, C.. Dayananda Sagar College of Engineering; IndiaFil: Bilachi, R.S.. Manipal Institute Of Technology; IndiaFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaLandes Bioscience2025-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/290283Hinojosa Vera, Kathleen Fabiola; Hema Kumar, C.; Bilachi, R.S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets; Landes Bioscience; Oxidative Medicine and Cellular Longevity; 2025; 1; 11-2025; 1-171942-09001942-0994CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1155/omcl/6710641info:eu-repo/semantics/altIdentifier/doi/10.1155/omcl/6710641info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:45:46Zoai:ri.conicet.gov.ar:11336/290283instacron: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:34982026-08-25 15:45:47.437CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
title Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
spellingShingle Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
Hinojosa Vera, Kathleen Fabiola
OBESITY
ADIPOSE MACROPHAGE
GENE EXPRESSION
PHENOTYPIC SWITCH
title_short Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
title_full Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
title_fullStr Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
title_full_unstemmed Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
title_sort Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets
dc.creator.none.fl_str_mv Hinojosa Vera, Kathleen Fabiola
Hema Kumar, C.
Bilachi, R.S.
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author Hinojosa Vera, Kathleen Fabiola
author_facet Hinojosa Vera, Kathleen Fabiola
Hema Kumar, C.
Bilachi, R.S.
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author_role author
author2 Hema Kumar, C.
Bilachi, R.S.
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author2_role author
author
author
author
dc.subject.none.fl_str_mv OBESITY
ADIPOSE MACROPHAGE
GENE EXPRESSION
PHENOTYPIC SWITCH
topic OBESITY
ADIPOSE MACROPHAGE
GENE EXPRESSION
PHENOTYPIC SWITCH
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Obesity-associated metabolic dysfunction is closely linked to chronic low-grade inflammation, or metaflammation, which is predominantly driven by changes in AT homeostasis. Macrophages, key components of the innate immune system, are central regulators of this inflammatory process. In lean AT, resident macrophages (AT-associated macrophages [ATMs]) exhibit an anti-inflammatory phenotype and support tissue homeostasis. However, during obesity, AT undergoes hypoxia, mechanical stress, and lipid overload, leading to immune cell infiltration and a phenotypic switch of ATMs toward a proinflammatory M1 profile. This shift contributes to systemic inflammation and obesity-associated metabolic risks. Here, we review the current understanding of macrophage polarization in obesity, highlighting the transcriptomic plasticity and functional heterogeneity of ATMs, their interactions within the AT microenvironment, and the formation of crown-like structures (CLSs) as a structural hallmark of AT inflammation. We also discuss the regulatory functions of transcription factors, such as hypoxia-inducible factor (HIF) 1α (HIF-1α) and peroxisome proliferator activated receptor gamma (PPARγ), that control the phenotypic switch of macrophages in healthy and obese ATs. Furthermore, we examined emerging macrophage subsets, such as CD9+ and Trem2+ lipid-associated macrophages (LAMs), and their dual roles in AT remodeling and inflammation. Understanding the complex network of macrophage activation in obese AT is essential for identifying therapeutic targets aimed at mitigating obesity-associated metabolic risk and restoring tissue function.
Fil: Hinojosa Vera, Kathleen Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Hema Kumar, C.. Dayananda Sagar College of Engineering; India
Fil: Bilachi, R.S.. Manipal Institute Of Technology; India
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description Obesity-associated metabolic dysfunction is closely linked to chronic low-grade inflammation, or metaflammation, which is predominantly driven by changes in AT homeostasis. Macrophages, key components of the innate immune system, are central regulators of this inflammatory process. In lean AT, resident macrophages (AT-associated macrophages [ATMs]) exhibit an anti-inflammatory phenotype and support tissue homeostasis. However, during obesity, AT undergoes hypoxia, mechanical stress, and lipid overload, leading to immune cell infiltration and a phenotypic switch of ATMs toward a proinflammatory M1 profile. This shift contributes to systemic inflammation and obesity-associated metabolic risks. Here, we review the current understanding of macrophage polarization in obesity, highlighting the transcriptomic plasticity and functional heterogeneity of ATMs, their interactions within the AT microenvironment, and the formation of crown-like structures (CLSs) as a structural hallmark of AT inflammation. We also discuss the regulatory functions of transcription factors, such as hypoxia-inducible factor (HIF) 1α (HIF-1α) and peroxisome proliferator activated receptor gamma (PPARγ), that control the phenotypic switch of macrophages in healthy and obese ATs. Furthermore, we examined emerging macrophage subsets, such as CD9+ and Trem2+ lipid-associated macrophages (LAMs), and their dual roles in AT remodeling and inflammation. Understanding the complex network of macrophage activation in obese AT is essential for identifying therapeutic targets aimed at mitigating obesity-associated metabolic risk and restoring tissue function.
publishDate 2025
dc.date.none.fl_str_mv 2025-11
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/11336/290283
Hinojosa Vera, Kathleen Fabiola; Hema Kumar, C.; Bilachi, R.S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets; Landes Bioscience; Oxidative Medicine and Cellular Longevity; 2025; 1; 11-2025; 1-17
1942-0900
1942-0994
CONICET Digital
CONICET
url http://hdl.handle.net/11336/290283
identifier_str_mv Hinojosa Vera, Kathleen Fabiola; Hema Kumar, C.; Bilachi, R.S.; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Macrophage Phenotypic Switch and Obesity‐Associated Metabolic Risk: Mechanisms and Targets; Landes Bioscience; Oxidative Medicine and Cellular Longevity; 2025; 1; 11-2025; 1-17
1942-0900
1942-0994
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://onlinelibrary.wiley.com/doi/10.1155/omcl/6710641
info:eu-repo/semantics/altIdentifier/doi/10.1155/omcl/6710641
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
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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