Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence
- Aurélie Villaret1,2,
- Jean Galitzky1,
- Pauline Decaunes1,
- David Estève1,
- Marie-Adeline Marques1,
- Coralie Sengenès1,
- Patrick Chiotasso3,
- Tamara Tchkonia4,
- Max Lafontan1,
- James L. Kirkland4 and
- Anne Bouloumié1
- 1Institut National de la Santé et de la Recherche Médicale (INSERM), U858, Institut de Médecine Moléculaire de Rangueil, Toulouse, France, and Université Paul Sabatier Toulouse-III, Toulouse, France;
- 2Laboratoires Sérobiologiques, Division of Cognis, Pulnoy, France;
- 3Chirurgie Générale et Digestive, CHU Purpan, Toulouse, France;
- 4Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota.
- Corresponding author: Anne Bouloumié, .
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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- Received March 23, 2010.
- Accepted July 28, 2010.
- © 2010 by the American Diabetes Association.
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