(A) The abundance of HIF2α and ATF4 in hepatocytes isolated from lean and NAFLD/NASH humans or WT mice.
(B) Effect of HIF2a repression on the expression of genes associated with lipogenesis in DFO-treated lean mouse hepatocytes.
Lipogenesis in DFO-treated human healthy (C) or NAFLD/NASH (D) hepatocytes after transfection with siRNA-HIF2a.
(E) Effects of HIF2α knockdown on the abundance of phosphorylated AKT and ATF4 in DFO-treated healthy human hepatocytes.
Effect of DFO treatment on lipogenesis in lean ATF4KO mouse hepatocytes (F) and lipogenesis gene abundance in siRNA-Atf4 treated healthy human hepatocytes (G).
Levels of triglyceride (H) and H&E staining (I) in livers, glucose tolerance (J), and insulin sensitivity (K) of 16wks WD ATF4f/f and AlbuminCre+ATF4f/f (Atf4ΔHep) mice. Representative images of n=6 per group (I). n=7–10 per group (J&K). Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, Student’s t-test. See also Figure S3.