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. Author manuscript; available in PMC: 2020 Nov 27.
Published in final edited form as: Cell. 2019 Nov 27;179(6):1276–1288.e14. doi: 10.1016/j.cell.2019.10.034

Figure 4. GPR146 Regulates SREBP2 Signaling Pathway and Plasma TC levels through ERK1/2 upon Feeding.

Figure 4.

(A-C) Fold induction of SREBP2 (A), HMGCR (B) and LDLR (C) mRNA levels in human hepatoma HepG2 cells upon serum stimulation in the presence or absence of MEK inhibitor PD0325901 (PD) (n=3 replicates per time point per experiment, representative of 3 independent experiments, by Student’s t-test).

(D) Western blot of mature SREBP2 in HepG2 cells upon serum stimulation in the presence or absence of PD0325901.

(E) Western blot showing CRISPR-induced depletion of ERK1, ERK2 or ERK1/2 in HepG2 cells in the presence or absence of serum stimulation.

(F-H) Fold induction of SREBP2 (F), HMGCR (G) and LDLR (H) mRNA levels in HepG2 cells lacking ERK1, ERK2 or ERK1/2 (n=3 replicates per genotype per experiment, representative of 3 independent experiments, by one-way ANOVA).

(I) Fold induction of HMGCR and LDLR mRNA level in HepG2 cells with recombinant expression of GPR146 or GFP (n=3 replicates per genotype per experiment, representative of 3 independent experiments, by Student’s t-test).

(J) Schedule of MEK inhibitor PD0325901 treatment in vivo.

(K and L) Plasma TC levels (K) and relative mRNA levels of hepatic Hmgcr, Ldlr and Srebp2 (L) in chow-fed female Gpr146+/+ mice and Gpr146−/− littermates upon 6-hour refeeding after a 16-hour fast, treated with vehicle or PD0325901 (5mg/kg Body Weight) for the period of time indicated (n=5 mice per group, by one-way ANOVA).

* p< 0.05, ** p< 0.01; bars in this figure indicate mean± s.d..