Surprisingly, livers from HF-fed Nrf2−/− mice did not exhibit an overt UPR, as evidenced by failure to increase mRNA and/or protein levels of Atf6 p90, Ire1, Atf4, Atf6 p50, Grp78, and Xbp1s compared with HF-fed Nrf2+/+ and/or RC-fed Nrf2−/− livers, and we suppose this failure occurs either because the UPR cannot be maintained as a consequence of extensive liver damage or because triggering of the UPR is fundamentally altered in Nrf2−/− livers. The gene discussed is ATF4; the disease is hydrops fetalis.