Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence.
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 adipo...
| Published in: | Diabetes Vol. 59; no. 11; pp. 2755 - 2764 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
American Diabetes Association
Nov2010
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105013381&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105013381 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00121797 1G6 jtl: Diabetes issn: 00121797 maglogo: N pubinfo: dt: Nov2010 vid: 59 iid: 11 pid: 1367 pub: American Diabetes Association place: Arlington, Virginia artinfo: ui: 105013381 NLM20713685 2010842842 10.2337/db10-0398 NLM20713685 PMC2963533 105013381 ppf: 2755 ppct: 9 formats: tig: atl: Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. aug: au: Villaret A Galitzky J Decaunes P Estève D Marques MA Sengenès C Chiotasso P Tchkonia T Lafontan M Kirkland JL Bouloumié A Villaret, Aurélie Galitzky, Jean Decaunes, Pauline Estève, David Marques, Marie-Adeline Sengenès, Coralie Chiotasso, Patrick Tchkonia, Tamara Lafontan, Max affil: Institut National de la Santé et de la Recherche Médicale, U858, Institut de Médecine Moléculaire de Rangueil, Toulouse, France sug: subj: Adipose Tissue Metabolism Adipose Tissue Pathology Cell Aging Physiology Obesity Metabolism Obesity Pathology Adipocytes Adipocytes Metabolism Adipocytes Pathology Adult Biopsy Body Mass Index Cytokines Female Genes Human Hypercholesterolemia Hypercholesterolemia Metabolism Hypercholesterolemia Pathology Hypertension Hypertension Metabolism Hypertension Pathology Immunohistochemistry Methods Inflammation Inflammation Metabolism Inflammation Pathology Male Middle Age Obesity Reference Values Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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