The serine phosphorylation of IRS-1 (Ser-307 and Ser-636 sites), which counteracted IRS-1 tyrosine phosphorylation and contributed to insulin resistance 53, was enhanced by HFD but suppressed by NR in WT mice but not in Fndc5-/- mice (Figure 3F). The gene discussed is FNDC5; the disease is Insulin resistance.