The observation that glucose tolerance and insulin sensitivity in HFD-fed DKO-BMT mice is only partially improved in contrast to the almost complete protection from HFD-induced glucose intolerance, insulin insensitivity, obesity, and macrophage infiltration observed in the organs of PDK2/4 DKO mice is suggestive that the beneficial effects of PDK deficiency are not totally due to inhibition of macrophage polarization. The gene discussed is PDK2; the disease is obesity due to melanocortin 4 receptor deficiency.