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

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 11; pp. 2755 - 2763
• Main Authors: Villaret, Aurélie, Galitzky, Jean, Decaunes, Pauline, Estève, David, Marques, Marie-Adeline, Sengenès, Coralie, Chiotasso, Patrick, Tchkonia, Tamara, Lafontan, Max, Kirkland, James L., Bouloumié, Anne
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2010
• Subjects: Abdomen; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipocytes - pathology; Adipose Tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adipose tissues; Adult; Angiogenesis; Antibodies; Biochemistry, Molecular Biology; Biological and medical sciences; Biopsy; Body fat; Body Mass Index; Care and treatment; Cell Aging; Cellular Senescence - physiology; Chemokine CCL20; Chemokine CCL20 - genetics; Diabetes; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Diagnosis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Female; Flow cytometry; Gastrointestinal surgery; Gene expression; Gene Expression Regulation; Genetic aspects; Human subjects; Humans; Hypercholesterolemia; Hypercholesterolemia - genetics; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; Hypertension; Hypertension - genetics; Hypertension - metabolism; Hypertension - pathology; Hypotheses; Hypoxia; Immunohistochemistry; Immunohistochemistry - methods; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Intra-Abdominal Fat; Intra-Abdominal Fat - metabolism; Intra-Abdominal Fat - pathology; Life Sciences; Male; Medical sciences; Metabolic diseases; Metabolism; Middle Aged; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Penicillin; Physiological aspects; Reference Values; Research design; Senescence; Subcutaneous Fat; Subcutaneous Fat - metabolism; Subcutaneous Fat - pathology; Vascular endothelial growth factor; France; Endocrinopathy; Human; Obesity; Endothelial cell; Senescence; Adipose tissue; Diabetes mellitus; Nutrition disorder; Gene expression; Nutritional status
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db10-0398

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.