Cargando…

Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity

OBJECTIVE: Defective caveolin-1 expression is now recognized as a cause of lipoatrophic diabetes in patients, due to primary caveolin gene mutations or secondary caveolin deficiency caused by PTRF/cavin gene defects. The goal of this study was to establish the relative contribution of endothelial ce...

Descripción completa

Detalles Bibliográficos
Autores principales: Briand, Nolwenn, Le Lay, Soazig, Sessa, William C., Ferré, Pascal, Dugail, Isabelle
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028344/
https://www.ncbi.nlm.nih.gov/pubmed/21270257
http://dx.doi.org/10.2337/db10-0856
_version_ 1782197167584182272
author Briand, Nolwenn
Le Lay, Soazig
Sessa, William C.
Ferré, Pascal
Dugail, Isabelle
author_facet Briand, Nolwenn
Le Lay, Soazig
Sessa, William C.
Ferré, Pascal
Dugail, Isabelle
author_sort Briand, Nolwenn
collection PubMed
description OBJECTIVE: Defective caveolin-1 expression is now recognized as a cause of lipoatrophic diabetes in patients, due to primary caveolin gene mutations or secondary caveolin deficiency caused by PTRF/cavin gene defects. The goal of this study was to establish the relative contribution of endothelial cells and adipocytes, both highly expressing caveolin-1 to the lipoatrophic phenotype of mice with global caveolin-1 gene invalidation (Cav1-KO). RESEARCH DESIGN AND METHODS: We compared adipose tissue development and metabolic phenotype of wild-type (WT), lipoatrophic Cav1-KO, and a murine model with specific rescue of caveolin-1 expression in endothelial cells (caveolin-1-reconstituted [Cav1-RC]). RESULTS: Defective adipose tissue development, reduced adipocyte size, and global alteration in adipose tissue gene expression that characterize lipoatrophic caveolin-1 null mice were still observed in Cav1-RC, indicating a prominent role of adipocyte-derived caveolin in lipoatrophy. We also observed that Cav1-KO adipose tissue contained an increased proportion of infiltrated macrophages compared with control mice, mostly with an alternate activation M2 phenotype. In contrast with defective lipid storage and lipoatrophy, macrophage infiltration was normalized in Cav1-RC mice, pointing to caveolin-1-dependent endothelium permeability as the causing factor for adipose tissue macrophage infiltration in this model. CONCLUSIONS: This is the first report of a specific role for adipocyte caveolin expression in lipid storage. Our study also shows that endothelium caveolin critically participates in the control of macrophage extravasation from the blood into adipose tissue, therefore establishing distinct roles depending on topology of caveolin expression in different cell types of adipose tissue.
format Text
id pubmed-3028344
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-30283442012-02-01 Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity Briand, Nolwenn Le Lay, Soazig Sessa, William C. Ferré, Pascal Dugail, Isabelle Diabetes Metabolism OBJECTIVE: Defective caveolin-1 expression is now recognized as a cause of lipoatrophic diabetes in patients, due to primary caveolin gene mutations or secondary caveolin deficiency caused by PTRF/cavin gene defects. The goal of this study was to establish the relative contribution of endothelial cells and adipocytes, both highly expressing caveolin-1 to the lipoatrophic phenotype of mice with global caveolin-1 gene invalidation (Cav1-KO). RESEARCH DESIGN AND METHODS: We compared adipose tissue development and metabolic phenotype of wild-type (WT), lipoatrophic Cav1-KO, and a murine model with specific rescue of caveolin-1 expression in endothelial cells (caveolin-1-reconstituted [Cav1-RC]). RESULTS: Defective adipose tissue development, reduced adipocyte size, and global alteration in adipose tissue gene expression that characterize lipoatrophic caveolin-1 null mice were still observed in Cav1-RC, indicating a prominent role of adipocyte-derived caveolin in lipoatrophy. We also observed that Cav1-KO adipose tissue contained an increased proportion of infiltrated macrophages compared with control mice, mostly with an alternate activation M2 phenotype. In contrast with defective lipid storage and lipoatrophy, macrophage infiltration was normalized in Cav1-RC mice, pointing to caveolin-1-dependent endothelium permeability as the causing factor for adipose tissue macrophage infiltration in this model. CONCLUSIONS: This is the first report of a specific role for adipocyte caveolin expression in lipid storage. Our study also shows that endothelium caveolin critically participates in the control of macrophage extravasation from the blood into adipose tissue, therefore establishing distinct roles depending on topology of caveolin expression in different cell types of adipose tissue. American Diabetes Association 2011-02 2011-01-21 /pmc/articles/PMC3028344/ /pubmed/21270257 http://dx.doi.org/10.2337/db10-0856 Text en © 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
Briand, Nolwenn
Le Lay, Soazig
Sessa, William C.
Ferré, Pascal
Dugail, Isabelle
Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
title Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
title_full Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
title_fullStr Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
title_full_unstemmed Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
title_short Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
title_sort distinct roles of endothelial and adipocyte caveolin-1 in macrophage infiltration and adipose tissue metabolic activity
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028344/
https://www.ncbi.nlm.nih.gov/pubmed/21270257
http://dx.doi.org/10.2337/db10-0856
work_keys_str_mv AT briandnolwenn distinctrolesofendothelialandadipocytecaveolin1inmacrophageinfiltrationandadiposetissuemetabolicactivity
AT lelaysoazig distinctrolesofendothelialandadipocytecaveolin1inmacrophageinfiltrationandadiposetissuemetabolicactivity
AT sessawilliamc distinctrolesofendothelialandadipocytecaveolin1inmacrophageinfiltrationandadiposetissuemetabolicactivity
AT ferrepascal distinctrolesofendothelialandadipocytecaveolin1inmacrophageinfiltrationandadiposetissuemetabolicactivity
AT dugailisabelle distinctrolesofendothelialandadipocytecaveolin1inmacrophageinfiltrationandadiposetissuemetabolicactivity