Adipose Tissue Endothelial Cells from Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence
- Aurélie Villaret, M.Sc.1,4,
- Jean Galitzky, Ph.D.1,
- Pauline Decaunes1,
- David Estève1,
- Marie-Adeline Marques1,
- Coralie Sengenès, Ph.D.1,
- Patrick Chiotasso, M.D.2,
- Tamara Tchkonia, Ph.D.3,
- Max Lafontan, Ph.D.1,
- James L. Kirkland, M.D., Ph.D.3 and
- Anne Bouloumié, Ph.D. ()1
- 1. Institut 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, Equipe n°1 AVENIR
- 2. Chirurgie générale et digestive, CHU Purpan, Toulouse, France
- 3. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Guggenheim 701A, Rochester, MN 55905, USA
- 4. Laboratoires Serobiologiques, Division of Cognis, Pulnoy, France
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 and visceral adipose tissue (SAT and 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 VEGFA neutralizing antibodies.
Conclusions: VAT-EC exhibit a more marked angiogenic and pro-inflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. Potentially, VAT-EC contribute to hypoxia and inflammation in VAT.
- Received March 23, 2010.
- Accepted July 28, 2010.
- Copyright © American Diabetes Association