Endoplasmic reticulum (ER) stress signal transduction (Modification of []). Genes considered in the liver of periparturient dairy cows in this study are shown in bold. ER stress in early lactating cows might be induced either by inflammation and/or high concentrations of NEFA deriving from plasma due to strong lipolysis in adipose tissue. In response to ER stress, the three ER stress sensors PKR-like ER kinase (PERK), inositol requiring 1 (IRE1), and activating transcription factor 6 (ATF6) are activated by dissociation from BiP. In turn, genes of the UPR including those considered in this study (ATF4, DDIT3, PDIA4, WARS, EDEM1, DNAJC3, HSPA5, CASP3, CASP8, CASP9, HERPUD1, BAK1, BAX) are up-regulated. Increased mRNA concentrations of FGF21 and target genes of NF-κB and Nrf2, which are also induced by ER stress in the liver of periparturient cows, have been recently reported [34, 35, 39, 40].