Moreover, and in contrast to its anti-inflammatory effects in other tissues, TGF-β/Smad3 signaling causes adipocyte hypertrophy, hyperplasia, and increased production of inflammatory cytokines, which together with TGF-β contribute to obesity-associated adipose tissue fibrosis [92,93]. This evidence concerns the gene SMAD3 and obesity due to melanocortin 4 receptor deficiency.