Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling

Autores
Barranco, Maria Manuela; Perdomo, Virginia; Zecchinati, Felipe; Manarin, Romina; Massuh, Greta; Sigal, Nicolás; Vignaduzzo, Silvana Edit; Mottino, Aldo Domingo; Villanueva, Silvina Stella Maris; Garcia, Fabiana
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: Multidrug resistance transporter 1 (Mdr-1) is a relevant component of the intestinal transcellular barrier that decreases absorption of oral drugs, thus modulating their bioavailability. Obese patients with metabolic disorders take medications that are subjected to intestinal metabolism and the Mdr-1–dependent barrier. This study evaluated the effect of a high-fat diet (HFD; 40% fat for 16 wk) on Mdr-1 expression and transport activity in C57BL/6 (C57) male mice. Comparable studies were performed in tumor necrosis factor α (TNF-α) receptor 1 knockout mice (R1KO) to delineate a possible role of TNF-α signaling. Methods: mRNA expression was evaluated by real-time polymerase chain reaction and protein levels by western blotting and immunohistochemistry. Mdr-1 activity was assessed using the everted intestinal sac model, with rhodamine 123 as the substrate. Statistical comparisons were made using the Student t test or one-way analysis of variance followed by the post hoc Tukey test. Results: Mdr-1 protein, as well as its corresponding Mdr1a and Mdr1b mRNA, was decreased in C57-HFD mice compared with controls. Immunohistochemical studies confirmed downregulation of Mdr-1 in situ. These results correlated with a 48% decrease in the basolateral to apical transport of rhodamine 123. In contrast, R1KO-HFD modified neither intestinal Mdr-1 mRNA nor its protein expression or activity. In addition, C57-HFD showed elevated intestinal TNF-α mRNA and protein (enzyme-linked immunosorbent assay) levels, whereas R1KO-HFD was undetectable or had a lower increase, respectively. Conclusions: This study demonstrated an impairment of the Mdr-1 intestinal barrier function induced by HFD as a consequence of downregulation of both Mdr-1 gene homologues, resulting in impaired Mdr-1 protein expression. Inflammatory response mediated by TNF-α receptor 1 signaling was likely involved.
Fil: Barranco, Maria Manuela. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Perdomo, Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Zecchinati, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Manarin, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina
Fil: Massuh, Greta. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina
Fil: Sigal, Nicolás. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina
Fil: Vignaduzzo, Silvana Edit. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Garcia, Fabiana. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Materia
HIGH-FAT DIET
INFLAMMATION
MDR-1
TNFR1
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:11336/223114
Acceder
id CONICETDig_57f977c6e8f5476e83be6a630591f7d7
oai_identifier_str oai:ri.conicet.gov.ar:11336/223114
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signalingBarranco, Maria ManuelaPerdomo, VirginiaZecchinati, FelipeManarin, RominaMassuh, GretaSigal, NicolásVignaduzzo, Silvana EditMottino, Aldo DomingoVillanueva, Silvina Stella MarisGarcia, FabianaHIGH-FAT DIETINFLAMMATIONMDR-1TNFR1https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Objectives: Multidrug resistance transporter 1 (Mdr-1) is a relevant component of the intestinal transcellular barrier that decreases absorption of oral drugs, thus modulating their bioavailability. Obese patients with metabolic disorders take medications that are subjected to intestinal metabolism and the Mdr-1–dependent barrier. This study evaluated the effect of a high-fat diet (HFD; 40% fat for 16 wk) on Mdr-1 expression and transport activity in C57BL/6 (C57) male mice. Comparable studies were performed in tumor necrosis factor α (TNF-α) receptor 1 knockout mice (R1KO) to delineate a possible role of TNF-α signaling. Methods: mRNA expression was evaluated by real-time polymerase chain reaction and protein levels by western blotting and immunohistochemistry. Mdr-1 activity was assessed using the everted intestinal sac model, with rhodamine 123 as the substrate. Statistical comparisons were made using the Student t test or one-way analysis of variance followed by the post hoc Tukey test. Results: Mdr-1 protein, as well as its corresponding Mdr1a and Mdr1b mRNA, was decreased in C57-HFD mice compared with controls. Immunohistochemical studies confirmed downregulation of Mdr-1 in situ. These results correlated with a 48% decrease in the basolateral to apical transport of rhodamine 123. In contrast, R1KO-HFD modified neither intestinal Mdr-1 mRNA nor its protein expression or activity. In addition, C57-HFD showed elevated intestinal TNF-α mRNA and protein (enzyme-linked immunosorbent assay) levels, whereas R1KO-HFD was undetectable or had a lower increase, respectively. Conclusions: This study demonstrated an impairment of the Mdr-1 intestinal barrier function induced by HFD as a consequence of downregulation of both Mdr-1 gene homologues, resulting in impaired Mdr-1 protein expression. Inflammatory response mediated by TNF-α receptor 1 signaling was likely involved.Fil: Barranco, Maria Manuela. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Perdomo, Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Zecchinati, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Manarin, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; ArgentinaFil: Massuh, Greta. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; ArgentinaFil: Sigal, Nicolás. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; ArgentinaFil: Vignaduzzo, Silvana Edit. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; ArgentinaFil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Garcia, Fabiana. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaElsevier Science Inc.2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/223114Barranco, Maria Manuela; Perdomo, Virginia; Zecchinati, Felipe; Manarin, Romina; Massuh, Greta; et al.; Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling; Elsevier Science Inc.; Nutrition; 111; 3-2023; 1-260899-9007CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0899900723000801info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nut.2023.112050info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:41:07Zoai:ri.conicet.gov.ar:11336/223114instacron: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 14:41:07.593CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
title Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
spellingShingle Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
Barranco, Maria Manuela
HIGH-FAT DIET
INFLAMMATION
MDR-1
TNFR1
title_short Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
title_full Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
title_fullStr Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
title_full_unstemmed Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
title_sort Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling
dc.creator.none.fl_str_mv Barranco, Maria Manuela
Perdomo, Virginia
Zecchinati, Felipe
Manarin, Romina
Massuh, Greta
Sigal, Nicolás
Vignaduzzo, Silvana Edit
Mottino, Aldo Domingo
Villanueva, Silvina Stella Maris
Garcia, Fabiana
author Barranco, Maria Manuela
author_facet Barranco, Maria Manuela
Perdomo, Virginia
Zecchinati, Felipe
Manarin, Romina
Massuh, Greta
Sigal, Nicolás
Vignaduzzo, Silvana Edit
Mottino, Aldo Domingo
Villanueva, Silvina Stella Maris
Garcia, Fabiana
author_role author
author2 Perdomo, Virginia
Zecchinati, Felipe
Manarin, Romina
Massuh, Greta
Sigal, Nicolás
Vignaduzzo, Silvana Edit
Mottino, Aldo Domingo
Villanueva, Silvina Stella Maris
Garcia, Fabiana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HIGH-FAT DIET
INFLAMMATION
MDR-1
TNFR1
topic HIGH-FAT DIET
INFLAMMATION
MDR-1
TNFR1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objectives: Multidrug resistance transporter 1 (Mdr-1) is a relevant component of the intestinal transcellular barrier that decreases absorption of oral drugs, thus modulating their bioavailability. Obese patients with metabolic disorders take medications that are subjected to intestinal metabolism and the Mdr-1–dependent barrier. This study evaluated the effect of a high-fat diet (HFD; 40% fat for 16 wk) on Mdr-1 expression and transport activity in C57BL/6 (C57) male mice. Comparable studies were performed in tumor necrosis factor α (TNF-α) receptor 1 knockout mice (R1KO) to delineate a possible role of TNF-α signaling. Methods: mRNA expression was evaluated by real-time polymerase chain reaction and protein levels by western blotting and immunohistochemistry. Mdr-1 activity was assessed using the everted intestinal sac model, with rhodamine 123 as the substrate. Statistical comparisons were made using the Student t test or one-way analysis of variance followed by the post hoc Tukey test. Results: Mdr-1 protein, as well as its corresponding Mdr1a and Mdr1b mRNA, was decreased in C57-HFD mice compared with controls. Immunohistochemical studies confirmed downregulation of Mdr-1 in situ. These results correlated with a 48% decrease in the basolateral to apical transport of rhodamine 123. In contrast, R1KO-HFD modified neither intestinal Mdr-1 mRNA nor its protein expression or activity. In addition, C57-HFD showed elevated intestinal TNF-α mRNA and protein (enzyme-linked immunosorbent assay) levels, whereas R1KO-HFD was undetectable or had a lower increase, respectively. Conclusions: This study demonstrated an impairment of the Mdr-1 intestinal barrier function induced by HFD as a consequence of downregulation of both Mdr-1 gene homologues, resulting in impaired Mdr-1 protein expression. Inflammatory response mediated by TNF-α receptor 1 signaling was likely involved.
Fil: Barranco, Maria Manuela. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Perdomo, Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Zecchinati, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Manarin, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina
Fil: Massuh, Greta. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina
Fil: Sigal, Nicolás. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina
Fil: Vignaduzzo, Silvana Edit. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Garcia, Fabiana. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
description Objectives: Multidrug resistance transporter 1 (Mdr-1) is a relevant component of the intestinal transcellular barrier that decreases absorption of oral drugs, thus modulating their bioavailability. Obese patients with metabolic disorders take medications that are subjected to intestinal metabolism and the Mdr-1–dependent barrier. This study evaluated the effect of a high-fat diet (HFD; 40% fat for 16 wk) on Mdr-1 expression and transport activity in C57BL/6 (C57) male mice. Comparable studies were performed in tumor necrosis factor α (TNF-α) receptor 1 knockout mice (R1KO) to delineate a possible role of TNF-α signaling. Methods: mRNA expression was evaluated by real-time polymerase chain reaction and protein levels by western blotting and immunohistochemistry. Mdr-1 activity was assessed using the everted intestinal sac model, with rhodamine 123 as the substrate. Statistical comparisons were made using the Student t test or one-way analysis of variance followed by the post hoc Tukey test. Results: Mdr-1 protein, as well as its corresponding Mdr1a and Mdr1b mRNA, was decreased in C57-HFD mice compared with controls. Immunohistochemical studies confirmed downregulation of Mdr-1 in situ. These results correlated with a 48% decrease in the basolateral to apical transport of rhodamine 123. In contrast, R1KO-HFD modified neither intestinal Mdr-1 mRNA nor its protein expression or activity. In addition, C57-HFD showed elevated intestinal TNF-α mRNA and protein (enzyme-linked immunosorbent assay) levels, whereas R1KO-HFD was undetectable or had a lower increase, respectively. Conclusions: This study demonstrated an impairment of the Mdr-1 intestinal barrier function induced by HFD as a consequence of downregulation of both Mdr-1 gene homologues, resulting in impaired Mdr-1 protein expression. Inflammatory response mediated by TNF-α receptor 1 signaling was likely involved.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
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/11336/223114
Barranco, Maria Manuela; Perdomo, Virginia; Zecchinati, Felipe; Manarin, Romina; Massuh, Greta; et al.; Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling; Elsevier Science Inc.; Nutrition; 111; 3-2023; 1-26
0899-9007
CONICET Digital
CONICET
url http://hdl.handle.net/11336/223114
identifier_str_mv Barranco, Maria Manuela; Perdomo, Virginia; Zecchinati, Felipe; Manarin, Romina; Massuh, Greta; et al.; Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling; Elsevier Science Inc.; Nutrition; 111; 3-2023; 1-26
0899-9007
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://linkinghub.elsevier.com/retrieve/pii/S0899900723000801
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nut.2023.112050
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc.
publisher.none.fl_str_mv Elsevier Science Inc.
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_ 1874774466413723648
score 13.265058

Publicaciones similares