Fig. 7.

Feeding inhibited SREBP-2 target sterol biosynthesis genes in a SHP-dependent manner. WT or SHP-KO mice were fasted for 12 h and then fed or fasted for 6 h and livers were collected. a Levels of phosphorylated ERK and total ERK levels are shown. b Fractionation study: Protein levels of SHP and SREBP-2 in nuclear and cytoplasmic fractions of mouse liver extracts were measured. c CoIP assays were done to monitor effect of feeding on interaction with endogenous SHP and SREBP-2. d-f ChIP: Effects of feeding and fasting in WT or SHP-KO mice on (d) gene activation histone marks at Hmgcr gene, (e) the mRNA levels of indicated genes, and (f) hepatic protein levels of HMGCR. Statistical significance was determined by the Student’s t-test, (SEM, n = 3-4, *P <0.05, **P <0.01, and NS, statistically not significant). g Mice were fasted for 12 h and then, treated with GW4064, FGF19, or feeding for 6 h and livers were collected to measure mRNA levels of Hmgcr, Srebp2, and Insig1 genes by q-RTPCR. Statistical significance was determined by the Student’s t-test, (SEM, n = 5 mice, *P <0.05, **P <0.01)