And, in liver, elevated activities of hepatic Akt and aPKC in HFF mice are important for activation of SREBP‐1c and lipogenesis,17, 20, 25, 41, 42, 43 and aPKC activation therein reflects both diet‐dependent increases in ceramide and hyperinsulinemia‐induced activation of IRS‐2/PI3K and production of PIP3, which directly displaces the inhibitory pseudosubstrate, and simultaneously promotes threonine‐555/560‐phosphorylation, of aPKC‐λ/ι/ζ.4, 6, 20. Here, IRS2 is linked to Hyperinsulinemia.