While depletion of ER calcium levels triggers the dissociation of MANF from the MANF‐GRP78 complex during ER stress, thereby facilitating its subsequent secretion.[37] In the present study, the primary hepatocytes of obese female offspring had decreased ER Ca2+ content levels in F1 and F2 mice than in CD mice, while the serum MANF levels in HFD‐F0 mice and the F1‐F2 female mice of paternal obesity were lower than in CD mice. This evidence concerns the gene MANF and obesity due to melanocortin 4 receptor deficiency.