INS and Insulin resistance: Whereas upon depletion of FGF21 in shChREBP + HFSD mice, a blunted response to insulin signaling (at the level of pAKT(S473) and pAKT (Thr308)) was observed in the liver, iWAT, and eWAT, demonstrating classical insulin resistance similar to HFSD group (Figs. 3, H, J, and K and S8, D–L).