Epidermal Growth Factor (EGF) signaling through the LET-23 receptor controls vulval and secretory development, healthspan, ovulation and many other processes. We have shown that it also controls lipid synthesis as
let-23(
sa62)gf animals have significantly lower qORO lipid staining than wild-type animals and the same level as
sbp-1(
ep79) lipid synthesis mutants. The
let-60(
n1046)gf mutation phenocopies that of
let-23(
sa62)gf suggesting that the LET-60/Ras pathway acts downstream of
let-23 in the control of lipid synthesis. A potential effector of EGF signaling is the lipid synthesis transcription factor SBP-1, an orthologue of human SREBP1. Active SBP-1 localises to the nucleus to promote expression of lipid synthesis genes and is inactivated by retention in the cytoplasm. We found that SBP-1::GFP localization in the intestine is biased towards inactive cytoplasmic form in a
let-60(
n1046)gf background and towards the active nuclear form in an
itr-1(
sy290)gf background. A double
let-60gf itr-1gf mutant shows a smaller but still significant cytoplasmic bias. Strangely,
let-23(
sa62)gf does not affect the cellular localization of SBP-1, possibly due to an interaction between the
let-23(
sa62)gf allele and the
sbp-1::gfp transgene. If LET-23 controls lipid synthesis via SBP-1, how is that mediated through changes in gene expression? We carried out an RNAseq analysis of
let-23(
sa62)gf,
sbp-1(
ep79)lf and wild-type strains. We predicted that if LET-23 acts via SBP-1 then a subset of the differentially expressed genes in
let-23(
sa62)gf animals would be similarly differentially expressed in
sbp-1(
ep79)lf animals. We found 154 and 1053 differentially expressed genes in
let-23(
sa62)gf and
sbp-1(
ep79)lf samples, respectively, compared with wildtype. Of these 65 were differentially expressed in the same direction in both
let-23(
sa62)gf and
sbp-1(
ep79)lf. The differentially expressed genes can be broadly categorized as insulin signaling responsive, expressed in intestine or neurons, or involved in innate immunity and bacterial defense. Two of the three most up (C27B7.6 and C27B7.7) and down (
pud-3 and
pud-4) regulated genes are also bidirectional, suggesting that they share LET-23 responsive regulatory elements. These RNAseq data show that the effect of overactive EGF signaling is in part the same as a loss of SBP-1 function, further supporting our model of SBP-1 acting downstream of LET-23 in its role in the control of lipid synthesis.