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 adipose tissue (VAT) biopsied in parallel from obese subjects.


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.
Villaret
Aurélie
A
Institut National de la Santé et de la Recherche Médicale, U858, Institut de Médecine Moléculaire de Rangueil, Toulouse, France.
Galitzky
Jean
J
Decaunes
Pauline
P
Estève
David
D
Marques
Marie-Adeline
MA
Sengenès
Coralie
C
Chiotasso
Patrick
P
Tchkonia
Tamara
T
Lafontan
Max
M
Kirkland
James L
JL
Bouloumié
Anne
A
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D016922:Cellular Senescence / Q000502:physiology*; D054418:Chemokine CCL20 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012016:Reference Values; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology
D054418:Chemokine CCL20