INS and obesity due to melanocortin 4 receptor deficiency: The data herein demonstrate that Aloxe3 ameliorated the diet-induced obesity and db/db diabetic phenotypes, at least in part, via a PPARγ-dependent mechanism — most prominently with regard to the insulin-sensitizing effects of Aloxe3. Aloxe3 overexpression and trehalose treatment in hepatocytes induced the PPARγ ligand 12-KETE at cellular concentrations that appear to be physiologically relevant (19).