Guar gum consumption increases hepatic nuclear SREBP2 and LDLr expression in pigs fed an atherogenic diet

The mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2) and low density lipoprotein receptor (LDLr) were examined in pigs fed an atherogenic control diet or the control diet supplemented with 10% guar gum (GG). Compared to the control group, GG consumption reduced (P<0.05) plasma total cholesterol (27%), LDL cholesterol (37%), and hepatic free cholesterol concentrations. GG consumption increased hepatic LDLr mRNA (1.8 fold, P=0.09) and protein (2 fold, P<0.05) expression in comparison to the control group. Hepatic SREBP2 mRNA expression was not altered (P>0.05) in response to GG consumption. While expression of the cytoplasmic mature form of SREBP2 was similar (P>0.05) between the two groups, GG consumption increased (P<0.05) the expression of the cytoplasmic precursor (3 fold) and nuclear active forms (1.5 fold) of the SREBP2. We conclude that a reduction in hepatic free cholesterol concentration in response to GG consumption enhances nuclear SREBP2 expression by post‐transcriptional events that are independent of the proteolytic release of the mature protein from the golgi apparatus. Furthermore, accumulation of nuclear SREBP2 increases the expression of hepatic LDLr and mediates the hypocholesterolemic effects associated with GG consumption. Supported by OMAFRA of Canada.