Endothelial Cells From Visceral Adipose Tissue Disrupt Adipocyte Functions in a Three-Dimensional Setting: Partial Rescue by Angiopoietin-1
- Vanessa Pellegrinelli1,2⇑,
- Christine Rouault1,2,3,4,
- Nicolas Veyrie5,
- Karine Clément1,2,3,4 and
- Danièle Lacasa1,2,3,4⇑
- 1INSERM, UMRS 872 Nutriomique, Paris, France
- 2Pierre et Marie Curie–Paris 6 University, Cordeliers Research Center, UMRS 872, Paris, France
- 3Paris Descartes University, UMRS 872, Paris, France
- 4Cardiometabolism and Nutrition Institute, Pitié Salpetrière Hospital, Paris, France
- 5General Surgery, Digestive, Metabolic, and Laparoscopic, Public Assistance Hospitals of Paris, Ambroise Paré Hospital, Versailles Saint-Quentin University, Boulogne-Billancourt, France
- Corresponding authors:
Vanessa Pellegrinelli, , and Danièle Lacasa, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0537/-/DC1.
- Received April 5, 2013.
- Accepted October 3, 2013.
- © 2014 by the American Diabetes Association.
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