OBESE ADIPOSE TISSUE SECRETOME PROMOTES ADIPOGENIC TRANSDIFFERANTIATION ON DEDIFFERENTIATED OSTEOBLASTS IN VITRO THROUGH TGF-β1

INTRODUCTION: Excessive adipose tissue accumulation during obesity is accompanied by pro-inflammatory mediators release, which can affect bone metabolism. We have previously demonstrated that the secretome of human subcutaneous obese adipose tissue (OATS) induces cellular regression of mature osteoblast towards a less committed state. However, the influence of OATS on adipogenic transdifferentiation is still unclear. OBJECTIVE: We evaluated the contribution of the secretome derived from subcutaneous adipose tissue from lean individuals (LATS) or obesity-bearing patients (OATS) in inducing adipocyte-like cells formation from dedifferentiated osteoblasts. METHODS: The HUPE-UERJ ethic committee approved this study (CAAE: 56302121.2.0000.5259). SAOS-2 osteoblasts were incubated with McCoy’s Medium 10% FBS (CTRL), supplemented with OATS or LATS (20%v/v). Cell viability and proliferation (48 h), and cell morphology (72 h) evaluated by MTT assay, DAPI+ cell count, and optical microscopy, respectively. In cells pretreated for 3 days with OATS or LATS adipogenic markers (7 days) and adipogenic differentiation (10 days) were quantified. RESULTS: Pre-treatment with OATS, but not with LATS, induced a spindle-shaped morphology and increased osteoblast proliferation, compared to CTRL. The pre-treatment with OATS increased adipogenic markers (CEBP-α, PPAR-γ) expression and promoted lipid droplets formation, enhancing perilipin expression in osteoblasts cultivated in adipogenic differentiation medium. The blockade of TGF-β1 in OATS inhibited all these effects. CONCLUSION: The adipose tissue from obesity-bearing individuals induces dedifferentiation of osteoblasts, favoring an adipogenic transdifferentiation through TGF-β1-mediated effect. Financial support: CNPq, DECIT-SUS, FAPERJ.