Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence.

Description

This study was conducted to investigate the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and intra-abdominal (visceral) adipose tissue (IAAT) biopsied in parallel from the same obese subjects. Paired biopsies from abdominal SAT or IAAT were obtained from subjects who had been weight stable for at least 3 months and included 29 women and 1 man (body mass index [BMI]=43.4 kg/m2; age=40.4 years). In vitro studies revealed marked hypertrophy of SAT compared with IAAT adipocytes in obese subjects. Expression of hypoxia-related genes, such as hypoxia-inducible factor (HIF)-1a and certain HIF1-responsive genes (vascular endothelial growth factor A [VEGFA] and GLUT1) was higher in IAAT than SAT adipocytes. Unexpectedly, capillary density was higher in human IAAT than SAT in obese subjects which is in contrast to the increased hypoxia in IAAT. Moreover, many of the genes encoding proinflammatory markers and angiogenic factor receptors were upregulated in IAAT-EC compared with SAT-EC. Finally, IAAT-EC had enhanced expression of cellular senescence markers which is associated with a proinflammatory and angiogenic state. These findings support the strong proinflammatory state associated with IAAT and suggest a possible role of EC in this relationship.