1. Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence
- Author
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Aurélie Villaret, Tamara Tchkonia, Patrick Chiotasso, Coralie Sengenès, James L. Kirkland, David Estève, Marie Adeline Marques, Max Lafontan, Pauline Decaunes, Jean Galitzky, Anne Bouloumié, Laboratoires Sérobiologiques, Division of Cognis, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chirurgie Générale et Digestive [Rangueil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Robert and Arlene Kogod Center on Aging, Mayo Clinic, and Simon, Marie Francoise
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MESH: Inflammation ,Male ,CD31 ,Endothelial lipase ,Biopsy ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,030204 cardiovascular system & hematology ,MESH: Hypertension ,Body Mass Index ,MESH: Biopsy ,0302 clinical medicine ,Reference Values ,Adipocytes ,MESH: Obesity ,Cellular Senescence ,0303 health sciences ,MESH: Middle Aged ,MESH: Reference Values ,MESH: Hypercholesterolemia ,Middle Aged ,MESH: Gene Expression Regulation ,Immunohistochemistry ,Endothelial stem cell ,Vascular endothelial growth factor A ,MESH: Cell Aging ,Adipose Tissue ,Hypertension ,Female ,medicine.symptom ,tissues ,Cell aging ,MESH: Adipose Tissue ,Adult ,medicine.medical_specialty ,Hypercholesterolemia ,Subcutaneous Fat ,Inflammation ,Intra-Abdominal Fat ,Biology ,MESH: Body Mass Index ,Proinflammatory cytokine ,03 medical and health sciences ,MESH: Subcutaneous Fat ,Internal medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Internal Medicine ,medicine ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Obesity ,MESH: Intra-Abdominal Fat ,MESH: Adipocytes ,030304 developmental biology ,MESH: Humans ,Chemokine CCL20 ,nutritional and metabolic diseases ,MESH: Immunohistochemistry ,MESH: Adult ,MESH: Chemokine CCL20 ,MESH: Male ,Metabolism ,Endocrinology ,Gene Expression Regulation ,MESH: Female - 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.
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- 2010
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