Moreover, in HFF and ob/ob mice and livers of T2DM humans, there are diet‐dependent increases in ceramide19, 20, 21 and phosphatidic acid (PA) that directly activate hepatic aPKC, which displaces Akt2 from the WD40/ProF platform,19, 20, 21, 43 thus impairing FoxO1 and PGC‐1α phosphorylation and thereby increasing their nuclear localization, transcriptional activities, and expression of PGC‐1α and gluconeogenic enzymes, PEPCK, and G6Pase. The gene discussed is FOXO1; the disease is type 2 diabetes mellitus.