Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence
| Autor: | Aurélie Villaret, Tamara Tchkonia, Patrick Chiotasso, Coralie Sengenès, James L. Kirkland, David Estève, Marie Adeline Marques, Max Lafontan, Pauline Decaunes, Jean Galitzky, Anne Bouloumié |
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| Přispěvatelé: | 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, Simon, Marie Francoise |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
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 |
| Zdroj: | Diabetes; Vol 59 Diabetes Diabetes, 2010, 59 (11), pp.2755-63. ⟨10.2337/db10-0398⟩ |
| ISSN: | 0012-1797 1939-327X |
| DOI: | 10.2337/db10-0398 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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