Finally, in the attempt to define the mechanism underlying the decreased PDH activity in tumors from MMTV-PyMT+/−; Sirt6+/− mice, we investigated whether this would reflect an increased expression of piruvate dehydrogenase kinase 1 (PDK1) or piruvate dehydrogenase kinase 4 (PDK4) (which both catalyze inhibitory phosphorylation of PDH), as previously reported as a consequence of reduced Sirt6 in intestinal cancer and in the heart, respectively [11, 37]. The gene discussed is PDK1; the disease is intestinal cancer.