CTBP-1 has been demonstrated to regulate the transcription of approximately 200 genes [21]. Chen et al [21] reported that ctpb-1(ok498) mutants have an extended lifespan, and that the loss of regulation of the lips-7 triacylglycerol (TAG) lipase in the ctbp-1 mutant could explain this aspect of the ctbp-1 mutant phenotype. In ctbp-1(ok498) mutant animals, lips-7 message is increased, and the resulting lipase overexpression caused animals to accumulate 16.8% less TAGs, and animals in which lips-7 had been inactivated by RNA interference had dramatically increased levels of TAGs [21]. We hypothesized that if the effect of loss of function of ctbp-1 on ethanol response, like its effect on lifespan, is due to its failure to down-regulate lips-7, then loss of lips-7 should have the opposite phenotype to loss of ctbp-1; that is, lips-7 mutants should display ethanol resistance and/or fast development of AFT. We found that lips-7(ok3110) mutant animals are both resistant to ethanol and fast developers of AFT, indicating that regulation of TAG levels is important for the development of AFT (Figure 2a). These results support the notion that the effect on lipase regulation via lips-7 is a mechanism of ctbp-1′s effect on AFT (Figure 2b).
