title: Endothelial cells from visceral adipose tissue disrupt adipocyte functions in a three-dimensional setting: partial rescue by angiopoietin-1.
abstract: 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.
authors.affiliation: INSERM, UMRS 872 Nutriomique, Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pellegrinelli
authors.forename: Christine
authors.initials: C
authors.lastname: Rouault
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veyrie
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Danièle
authors.initials: D
authors.lastname: Lacasa
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology*; D042683:Angiopoietin-1 / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007328:Insulin; D008066:Lipolysis / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D007328:Insulin; D012333:RNA, Messenger