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SECRETORY FACTORS PRODUCED BY STROMAL CULTURES OF HUMAN OMENTAL ADIPOSE TISSUE INHIBIT ADIPOSE DIFFERENTIATION
Author(s) -
Pickering R Taylor,
Lee MiJeong,
Jager Michal,
Layne Matthew,
Fried Susan K
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.126.7
Subject(s) - adipose tissue , adipocyte , stromal cell , adipose tissue macrophages , medicine , endocrinology , stromal vascular fraction , chemistry , biology , white adipose tissue
The size of visceral adipose tissues (VAT) is associated with risk for metabolic disease. As compared to subcutaneous, VATs have a limited capacity to expand by hyperplasia, leading to adipocyte hypertrophy, inflammation and tissue dysfunction. In contrast to adipose stem cells (ASCs) derived from the stromal fraction of human abdominal subcutaneous (Abdsc) adipose tissue, the visceral (omental (Om)) ASCs differentiate very poorly (on average only ~30% vs ~90%). We wanted to test the hypothesis that Om adipose tissue secretes factors that inhibit differentiation of human adipose progenitor cells. We differentiated the ASCs isolated from Abdsc tissue in a standard cocktail with 50% conditioned media (CM) from paired samples (n=8) of Om and Abdsc adipose tissue (7 Females, 1 Male BMI > 35), 25% CM from paired samples of ASCs (n=13) or control media throughout the 14d of differentiation. Differentiation was determined by triglyceride accumulation. IL‐6, Activin A, and TGFB levels were measured by ELISA, Western blot, and PAI‐1 Luciferase reporter assay, respectively. Omental tissue CM reduced differentiation to a greater extent compared to Abdsc [51±6 (Om) vs 111±12 (Absc) vs. control (171 mgTG/mgDNA)]. CM from Om ASCs suppressed differentiation more than CM from Abdsc [46±10 (Om) vs 26±5 (Sc) %suppression, n=13, p<0.05) and the magnitude of the effect correlated with the capacity of donors cells to differentiate (R2=0.4, p<0.01, n=17). As expected IL‐6 concentrations were much higher in CM from Om tissue and ASCs, but addition of IL‐6 did not inhibit differentiation. Members of the TGFB family, such as activin A and TGFB, are known inhibitors of adipogenesis, and we found that they were more highly expressed in Om ASCs. The concentration of activin A (0.9±0.2 AU vs 0.4±0.1 AU, n=9, p<0.05) and TGFB (1138±130 vs 539±65 AU n=13, p<0.001) were enriched in Om ASC conditioned media. Collectively, these data suggest that paracrine and autocrine production of TGFB and activin A, among other factors, produced by Om adipose tissue limit healthy adipose expansion and remodeling of human visceral adipose tissues.