Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence

Institut National de la Santé et de la Recherche Médicale, U858, Institut de Médecine Moléculaire de Rangueil, Toulouse, France.
Diabetes (Impact Factor: 8.1). 11/2010; 59(11):2755-63. DOI: 10.2337/db10-0398
Source: PubMed


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.
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.
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.
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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Available from: Jean Galitzky, Oct 06, 2015
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    • "Numerous cell types exist in adipose tissue depots, including stem cells, fibroblasts, MSC, ET cells, and immune infiltrating cells (Rink et al., 1996; Harasymiak- Krzyzanowska et al., 2013), although the characteristics of cells populating adipose tissue can vary depending on the site and microenvironment (Villaret et al., 2010). These other cells may contribute to adipokine production . "
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    • "In agreement with such a hypothesis, the present data show that hypoxic culture conditions mimicked the OmATM phenotype in ScATM, i.e. up-regulation of IL-6, VEGFA and LYVE-1. Interestingly, vascular network and endothelial cell number were found to be higher in OmAT versus ScAT [30]. Compared to OmATM, ScATM were characterized by higher expression of matrix remodeling/fibrosis-related genes, including TGFβ1 as well as MMP-2 and -9. "
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    • "It is already shown that insulin resistance is associated with chronic inflammation characterized by abnormal production of proinflammatory cytokines and acute phase reactants62 by several cell types, such as adipocytes and macrophages. Also, an increasing body of evidence reveals accumulation of senescent preadipocytes and ECs in the fat tissue of obese and aging subjects, which generate increased amount of cytokines and chemokines which appear to be capable of activating immune responses.63,64 Several rodent studies demonstrate that an increase in adipose tissue macrophages worsens insulin sensitivity.65,66 "
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