Figure 5.

Elevated TGF-β/Smad3 signaling causes adipocyte hypertrophy, hyperplasia and elevated pro-inflammatory cytokines production. These cytokines interfere with insulin signaling and promote the recruitment of M1 pro-inflammatory macrophages to the WAT. Smad3 deficiency ameliorates the chronic low-grade inflammation and insulin resistance by recruiting M2 protective macrophages and reducing pro-inflammatory cytokines expression from the adipocytes. Smad3 deficiency also upregulates the mRNA level of insulin-mimetic visfatin while decreasing resistin (insulin-desentizer).