As shown in Figure 2H,J, the protein levels of p‐PERK/PERK, p‐EIF2α/EIF2α, ATF4, and CHOP were significantly raised in the liver from the HFD‐F0 mice and their F1‐F2 female offspring, suggesting that ER stress and the PERK‐p‐EIF2α‐ATF4‐CHOP pathway may contribute to the glucose metabolic dysfunction upon paternal obesity. Here, ATF4 is linked to obesity due to melanocortin 4 receptor deficiency.