Figure 6. GPR146 Deficiency Protects Against Hypercholesterolemia and Atherosclerosis in LDLR-deficient Mice.

(A and C) Plasma TC levels of Gpr146 whole-body knockout male (A) and female (C) mice lacking LDLR fed chow or western diet (WD) for 16 weeks (n=6–10 mice per group, by one-way ANOVA).

(B and D) HDL and VLDL/LDL fractions in plasma of Gpr146 whole-body knockout male (B) and female (D) mice lacking LDLR were separated, and cholesterol levels were measured in both fractions (n=6–10 mice per group, by one-way ANOVA).

(E) Representative images of plasma (top layer) isolated from Gpr146^+/+ and Gpr146^−/− male mice lacking LDLR fed WD for 16 weeks.

(F and G) Western blot (F) and relative quantification (G) of SREBP2 precursor (P-SREBP2), mature SREBP2 (M-SREBP2), pERK1/2 and total ERK1/2 in livers of 6-hour refed male Gpr146^+/+ mice and Gpr146^−/− littermates lacking LDLR upon chow feeding (n=6 mice per group, by Student’s t-test).

(H) Quantitative polymerase chain reaction (qPCR) expression analysis of cholesterol biosynthetic genes in liver of 6-hour refed male and female Gpr146^+/+ mice and Gpr146^−/− littermates lacking LDLR upon chow feeding (n=6–7 mice per group, by Student’s t-test).

(I and L) Representative images of aortas before and after Oil Red O staining in Gpr146 wild type and whole-body knockout male (I) and female (L) mice lacking LDLR fed WD for 16 weeks.

(J and M) Quantification of aortic lesion areas (expressed as a percentage of the lumen area in full-length aorta) in male (J) and female (M) mice (n=6–10 mice per group, by Student’s t-test).

(K and N) Scatter plot of plasma total cholesterol levels and aortic lesion areas in male (K) and female mice (N) lacking LDLR.

* p< 0.05, ** p< 0.01; bars in A-D, G, J and M indicate mean± s.d., bars in H indicate mean± s.e.m..