Endothelial Cells From Visceral Adipose Tissue Disrupt Adipocyte Functions in a Three-Dimensional Setting: Partial Rescue by Angiopoietin-1

• Published in: Diabetes (New York, N.Y.) Vol. 63; no. 2; pp. 535 - 549
• Main Authors: Pellegrinelli, Vanessa, Rouault, Christine, Veyrie, Nicolas, Clément, Karine, Lacasa, Danièle
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2014
• Subjects: Adipocytes - physiology; Adipose Tissue - cytology; Angiopoietin-1 - pharmacology; Animals; Biological and medical sciences; Cell Culture Techniques; Cells; Diabetes. Impaired glucose tolerance; Effects; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial Cells - physiology; Endothelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Experiments; Genotype & phenotype; Growth factors; Humans; Identification and classification; Inflammation; Insulin; Lipolysis - physiology; Medical research; Medical sciences; Medicine, Experimental; Molecules; Obesity; Obesity - metabolism; Physiological aspects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tissues; Endocrinopathy; Adipocyte; Endothelial cell; Adipose tissue; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db13-0537

During obesity, chronic inflammation of human white adipose tissue (WAT) is associated with metabolic and vascular alterations. Endothelial cells from visceral WAT (VAT-ECs) exhibit a proinflammatory and senescent phenotype and could alter adipocyte functions. We aimed to determine the contribution of VAT-ECs to adipocyte dysfunction related to inflammation and to rescue these alterations by anti-inflammatory strategies. We developed an original three-dimensional setting allowing maintenance of unilocular adipocyte functions. Coculture experiments demonstrated that VAT-ECs provoked a decrease in the lipolytic activity, adipokine secretion, and insulin sensitivity of adipocytes from obese subjects, as well as an increased production of several inflammatory molecules. Interleukin (IL)-6 and IL-1β were identified as potential actors in these adipocyte alterations. The inflammatory burst was not observed in cocultured cells from lean subjects. Interestingly, pericytes, in functional interactions with ECs, exhibited a proinflammatory phenotype with diminished angiopoietin-1 (Ang-1) secretion in WAT from obese subjects. Using the anti-inflammatory Ang-1, we corrected some deleterious effects of WAT-ECs on adipocytes, improving lipolytic activity and insulin sensitivity and reducing the secretion of proinflammatory molecules. In conclusion, we identified a negative impact of VAT-ECs on adipocyte functions during human obesity. Therapeutic options targeting EC inflammation could prevent adipocyte alterations that contribute to obesity comorbidities.