Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue

Summary: White adipose tissue (WAT) mass is determined by adipocyte size and number. While adipocytes are continuously turned over, the mechanisms controlling fat cell number in WAT upon weight changes are unclear. Herein, prospective studies of human subcutaneous WAT demonstrate that weight gain increases both adipocyte size and number, but the latter remains unaltered after weight loss. Transcriptome analyses associate changes in adipocyte number with the expression of 79 genes. This gene set is enriched for growth factors, out of which one, transforming growth factor-β3 (TGFβ3), stimulates adipocyte progenitor proliferation, resulting in a higher number of cells undergoing differentiation in vitro. The relevance of these observations was corroborated in vivo where Tgfb3+/− mice, in comparison with wild-type littermates, display lower subcutaneous adipocyte progenitor proliferation, WAT hypertrophy, and glucose intolerance. TGFβ3 is therefore a regulator of subcutaneous adipocyte number and may link WAT morphology to glucose metabolism. : The mechanisms regulating adipocyte number upon increases in white adipose tissue mass are not known. Here, by combining prospective clinical studies with cell and animal models, Petrus et al. report that transforming growth factor-β3 increases adipocyte precursor proliferation and thereby enables hyperplastic white adipose tissue expandability. Keywords: adipogenesis, growth factor, cellularity, glucose tolerance, obesit