TGFB1 and obesity due to melanocortin 4 receptor deficiency: TGF-β1 which is enhanced in human obesity and primarily released by WAT macrophages,26 which also secrete matrix metalloproteinase-9 responsible for the proteolytic activation of its latent form,27 is implicated in ECM homeostasis28 and fibrosis.29, 30, 31 Also, the upregulation of HIF-1α observed in hypoxic conditions could represent a driving phenomenon for WAT fibrosis development.