Figure 4. Steatosis in response to chronic ER stress does not require Srebp activation.

A. The activation pathways for the nSrebp and nAtf6 transcription factors utilize common components. * indicates components targeted in our studies using either a morpholino (mo) or mutant (mt). B. Srebp1 and Srebp2 target genes were assessed in at least 3 clutches of RNA isolated from whole larvae (left) and dissected livers (right). Expression in foigr mutants was normalized to wild-type siblings (grey bars) and expression in tunicamycin treated larvae was normalized to DMSO treated siblings (black bars). The level of expression in the respective controls was set to 1 (horizontal bar). * indicates p<0.01 by a 1 sampled t-test. C. The effect of scap morpholino injection on steatosis in three models (fasting, chronic tunicamycin and foigr mutation) was assessed. First, scap morphants and uninjected siblings were fasted until 6 dpf (left) or, second, they were treated with tunicamycin or DMSO from 3–5 dpf (center). Third, scap morpholino was injected into foigr mutants and wild-type siblings (right). All larvae were collected on 5 dpf, whole mount stained with oil red O and scored for steatosis. The number larvae scored positive larvae (black) and negative (white) are plotted. The percent of fish with steatosis is indicated below each bar. ** indicates a p <0.001 by Fisher’s exact test, ns: not significant.