Figure 2.

PAR2 deficiency suppresses hypercholesterolemia and enhances reverse cholesterol transport in liver in HFD-fed mice. Male C57BL/6 wild type (WT-open bars) and PAR2-KO (KO-black bars) mice were fed 60% high fat diet (HFD, n = 10–14) for 16 weeks. (A) At the 16 week endpoint, plasma was obtained from non-fasted mice at Z+4 time point and assayed for total cholesterol. (B) Quantitative PCR (ΔΔCT) of hepatic Par2 mRNA from mice fed normal diet (ND) or HFD for 16 weeks, normalized to β-actin. Plasma cholesterol significantly correlated with hepatic Par2 expression from mice fed both ND and HFD. Linear regression analysis was performed and least-squares lines, R² values and P values for the slope are shown. (C) Livers from mice in A were harvested and weighed at the 16 week endpoint and assayed for mg cholesterol per g of liver tissue and total liver cholesterol content. (D) Hepatic transporters and enzymes controlling cholesterol flux and synthesis pathways affected by PAR2-deficiency in livers of mice fed a HFD diet for 16 weeks. (E) Quantitative PCR (ΔΔCT) of mRNA from mouse liver (normalized to β-actin mRNA) for Hmgcs1 (3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1), Hmgcr (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), Hsl (Hormone Sensitive Lipase), Npc1 (NPC intracellular cholesterol transporter 1), Abcg5 (ATP-binding cassette, sub-family G member 5), Abcg8 (ATP-binding cassette, sub-family G member 8), Abcb11 (ATP-binding cassette, sub-family B, member 11), Abcb4 (ATP-binding cassette, sub-family B, member 4), Ldlr (low-density lipoprotein receptor), Srb1 (scavenger receptor class B, member 1) in WT and PAR2-KO mice fed HFD for 16 weeks. (F) Mean fecal bile acid content from HFD-fed mice in A during a two-week collection period. All data are represented as mean ± SEM; Unpaired 2-tailed T-tests were performed,*P < 0.05, ***P < 0.001, ****P < 0.0001.