Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence
Open Access
- 16 August 2010
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 59 (11), 2755-2763
- https://doi.org/10.2337/db10-0398
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.Keywords
This publication has 37 references indexed in Scilit:
- Mechanisms of obesity and related pathologies: The macro‐ and microcirculation of adipose tissueThe FEBS Journal, 2009
- GPIHBP1, a GPI-anchored protein required for the lipolytic processing of triglyceride-rich lipoproteinsJournal of Lipid Research, 2009
- PPARγ in the endothelium regulates metabolic responses to high-fat diet in miceJCI Insight, 2008
- Role of Body Fat Distribution and the Metabolic Complications of ObesityJournal of Clinical Endocrinology & Metabolism, 2008
- Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of ChylomicronsCell Metabolism, 2007
- Increased Infiltration of Macrophages in Omental Adipose Tissue Is Associated With Marked Hepatic Lesions in Morbid Human ObesityDiabetes, 2006
- Angiogenesis Inhibitor, TNP-470, Prevents Diet-Induced and Genetic Obesity in MiceCirculation Research, 2004
- From Blood Monocytes to Adipose Tissue-Resident MacrophagesDiabetes, 2004
- Angiogenesis in an in vivo model of adipose tissue developmentThe FASEB Journal, 2004
- Adipose tissue mass can be regulated through the vasculatureProceedings of the National Academy of Sciences of the United States of America, 2002