Effects of interleukin-6 and tumor necrosis factor- on the expression of angiogenic and collagenolytic factors in premature and mature adipocytes

Objective: The remodeling of the vascular network and collagen in the extracellular matrix is closely associated with the expansion and dysfunction of adipose tissue. In the present study, we investigated the effects of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha on the expression of angiogenic factors, collagen, and collagenase and its endogenous inhibitor in premature and mature adipocytes. Methods: Premature and mature adipocytes were differentiated from 3T3-L1 cells and stimulated with IL-6 or TNF-alpha to mimic the early and late phases of obesity development. The levels of expression of angiogenic factors, including vascular endothelial cell growth factor a (Vegfa), hepatocyte growth factor (Hgf), angiopoietin (Angpt)1, and Angpt2, as well as type I collagen, matrix metallopeptidase (Mmp) 13, and tissue inhibitor of Mmp (Timp) 1, were determined using real-time reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. Human umbilical vein endothelial cells were grown with the culture supernatant of adipocytes stimulated with/without IL-6 or TNF-alpha, and the formation of tube structures was evaluated. Results: IL-6 and TNF-alpha induced the expression of Vegfa, Hgf, and Angpt2 and decreased the expression of Angpt1 in premature adipocytes, whereas, they decreased the expression of Vegfa and Hgf in mature adipocytes. The culture supernatant of IL-6- or TNF-alpha-stimulated premature adipocytes induced the formation of tube structures. IL-6 and TNF-alpha had no effects on type I collagen expression in both premature and mature adipocytes but suppressed the expression of Mmp13 and Timp1 in mature and premature adipocytes, respectively. Conclusion: The effects of IL-6 and TNF-alpha on the expression of angiogenic and collagenolytic factors differed between premature and mature adipocytes. This finding suggests that these inflammatory cytokines induce expansion and dysfunction of adipose tissue via angiogenesis and collagen turnover in premature and mature adipocytes. (C) 2020 Elsevier Inc. All rights reserved.