ATF4 and colitis: However, intervention with melatonin caused a reduction in colitis-associated oxidative stress, as observed by a significant decrease in Grp78, Xbp1, and Atf4 and an increase in Nrf2, Nqo-1, and Ho-1 levels in the colon of mice (Figure 4D–H), substantiating the antioxidant effect of melatonin on DSS-mediated colitis in obese mice.