The hypocholesterolemic effects of guar gum consumption are mediated by increased nuclear form of sterol regulatory element binding protein 2 (SREBP2) in the pig model

Abstract

To investigate the molecular basis for the hypocholesterolemic effects of guar gum (GG) consumption, fourteen grower boars were fed an atherogenic basal (control) diet supplemented with 10% GG for 30 days according to a completely randomized block design. GG consumption lowered (P < 0.05) plasma total cholesterol (78.45 ± 6.31 vs. 110.02 ± 5.56 mg/dl) and LDL cholesterol (41.03 ± 6.22 vs. 64.97 ± 5.83 mg/dl) concentrations in comparison to the control diet. Real time RT-PCR and immunoblot analyses were used to quantify the hepatic mRNA and protein abundance of SREBP2 and its target genes, 3-hydroxy- 3methylglutaryl coenzyme A reductase (HMG-CoAr) and low-density lipoprotein receptor (LDLr). SREBP2 mRNA expression was similar (P = 0.89) between the control and the GG-supplemented groups. GG consumption increased the mRNA expression of HMG-CoAr (8-fold, P = 0.04) and LDLr (1.5 fold, P = 0.20) in comparison to the control groups. GG consumption increased (1.5 fold, P = 0.02) the nuclear form of SREBP2 in comparison to the control group. While no difference (P = 0.88) in HMG-CoAr protein abundance was detected, LDLr protein abundance was increased in the GG group (1.8 fold, P = 0.04) in comparison to the control group. These results suggest that the hypocholesterolemic effects of GG are partially mediated by increased amount of the nuclear, active form of hepatic SREBP2.