Adipose tissue endothelial cells from obese human subjects

Differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence

Aurélie Villaret, Jean Galitzky, Pauline Decaunes, David Estève, Marie Adeline Marques, Coralie Sengenès, Patrick Chiotasso, Tamara Tchkonia, Max Lafontan, James L Kirkland, Anne Bouloumié

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

OBJECTIVE - Regional differences among adipose depots in capacities for fatty acid storage, susceptibility to hypoxia, and inflammation likely contribute to complications of obesity. We defined the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) biopsied in parallel from obese subjects. RESEARCH DESIGN AND METHODS - The architecture and properties of the fat tissue capillary network were analyzed using immunohistochemistry and flow cytometry. CD34 +/CD31+ EC were isolated by immunoselection/depletion. Expression of chemokines, adhesion molecules, angiogenic factor receptors, as well as lipogenic and senescence-related genes were assayed by real-time PCR. Fat cell size and expression of hypoxia-dependent genes were determined in adipocytes from both fat depots. RESULTS - Hypoxia-related genes were more highly expressed in VAT than SAT adipocytes. VAT adipocytes were smaller than SAT adipocytes. Vascular density and EC abundance were higher in VAT. VAT-EC exhibited a marked angiogenic and inflammatory state with decreased expression of metabolism-related genes, including endothelial lipase, GPIHBP1, and PPAR gamma. VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and γ-H2AX, and decreased expression of SIRT1. Exposure to VAT adipocytes caused more EC senescence-associated β-galactosidase activity than SAT adipocytes, an effect reduced in the presence of vascular endothelial growth factor A (VEGFA) neutralizing antibodies. CONCLUSIONS - VAT-EC exhibit a more marked angiogenic and proinflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. VAT-EC may contribute to hypoxia and inflammation in VAT.

Original languageEnglish (US)
Pages (from-to)2755-2763
Number of pages9
JournalDiabetes
Volume59
Issue number11
DOIs
StatePublished - Nov 2010

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Intra-Abdominal Fat
Cell Aging
Adipose Tissue
Endothelial Cells
Adipocytes
Gene Expression
Subcutaneous Fat
Genes
Fats
Galactosidases
Inflammation
Angiogenesis Inducing Agents
PPAR gamma
Neutralizing Antibodies
Lipase
Cell Size
Chemokines
Vascular Endothelial Growth Factor A
Real-Time Polymerase Chain Reaction
Flow Cytometry

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Adipose tissue endothelial cells from obese human subjects : Differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. / Villaret, Aurélie; Galitzky, Jean; Decaunes, Pauline; Estève, David; Marques, Marie Adeline; Sengenès, Coralie; Chiotasso, Patrick; Tchkonia, Tamara; Lafontan, Max; Kirkland, James L; Bouloumié, Anne.

In: Diabetes, Vol. 59, No. 11, 11.2010, p. 2755-2763.

Research output: Contribution to journalArticle

Villaret, A, Galitzky, J, Decaunes, P, Estève, D, Marques, MA, Sengenès, C, Chiotasso, P, Tchkonia, T, Lafontan, M, Kirkland, JL & Bouloumié, A 2010, 'Adipose tissue endothelial cells from obese human subjects: Differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence', Diabetes, vol. 59, no. 11, pp. 2755-2763. https://doi.org/10.2337/db10-0398
Villaret, Aurélie ; Galitzky, Jean ; Decaunes, Pauline ; Estève, David ; Marques, Marie Adeline ; Sengenès, Coralie ; Chiotasso, Patrick ; Tchkonia, Tamara ; Lafontan, Max ; Kirkland, James L ; Bouloumié, Anne. / Adipose tissue endothelial cells from obese human subjects : Differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. In: Diabetes. 2010 ; Vol. 59, No. 11. pp. 2755-2763.
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AU - Villaret, Aurélie

AU - Galitzky, Jean

AU - Decaunes, Pauline

AU - Estève, David

AU - Marques, Marie Adeline

AU - Sengenès, Coralie

AU - Chiotasso, Patrick

AU - Tchkonia, Tamara

AU - Lafontan, Max

AU - Kirkland, James L

AU - Bouloumié, Anne

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N2 - OBJECTIVE - Regional differences among adipose depots in capacities for fatty acid storage, susceptibility to hypoxia, and inflammation likely contribute to complications of obesity. We defined the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) biopsied in parallel from obese subjects. RESEARCH DESIGN AND METHODS - The architecture and properties of the fat tissue capillary network were analyzed using immunohistochemistry and flow cytometry. CD34 +/CD31+ EC were isolated by immunoselection/depletion. Expression of chemokines, adhesion molecules, angiogenic factor receptors, as well as lipogenic and senescence-related genes were assayed by real-time PCR. Fat cell size and expression of hypoxia-dependent genes were determined in adipocytes from both fat depots. RESULTS - Hypoxia-related genes were more highly expressed in VAT than SAT adipocytes. VAT adipocytes were smaller than SAT adipocytes. Vascular density and EC abundance were higher in VAT. VAT-EC exhibited a marked angiogenic and inflammatory state with decreased expression of metabolism-related genes, including endothelial lipase, GPIHBP1, and PPAR gamma. VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and γ-H2AX, and decreased expression of SIRT1. Exposure to VAT adipocytes caused more EC senescence-associated β-galactosidase activity than SAT adipocytes, an effect reduced in the presence of vascular endothelial growth factor A (VEGFA) neutralizing antibodies. CONCLUSIONS - VAT-EC exhibit a more marked angiogenic and proinflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. VAT-EC may contribute to hypoxia and inflammation in VAT.

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