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Biochemical, Molecular, and Genetic Mechanisms

Guar Gum Consumption Increases Hepatic Nuclear SREBP2 and LDL Receptor Expression in Pigs Fed an Atherogenic Diet¹

² Centre for Nutrition Modelling, Department of Animal and Poultry Science and Departments of ³ Human Health and Nutritional Science and ⁴ Food Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1; ⁵ Food Research Program, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada N1G 5C9; and ⁶ Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4

^* To whom correspondence should be addressed. E-mail: trideout{at}uoguelph.ca or mfan{at}uoguelph.ca.

To gain insight into the regulation of hepatic sterol-responsive genes that are thought to mediate the hypocholesterolemic effects of guar gum (GG) consumption, the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDLr), and scavenger receptor class B, type 1 (SR-B1) were examined in pigs consuming an atherogenic control diet or the control diet supplemented with 10% GG. Compared with the control group, GG consumption reduced (P < 0.05) plasma total cholesterol and LDL cholesterol concentrations by 27 and 37%, respectively. Furthermore, hepatic free cholesterol concentration was lower (P < 0.05) in the GG-fed pigs in comparison with the control group. GG consumption increased hepatic LDLr mRNA (1.5-fold of the control, P = 0.09) and protein (2-fold of the control, P < 0.05) expression in comparison with the control group. However, GG consumption reduced hepatic SR-B1 mRNA to 36% of the control (P < 0.05) expression but did not affect (P = 0.19) SR-B1 protein abundance in comparison with the control group. Although SREBP2 mRNA expression was similar (P = 0.89) in the 2 groups, GG consumption increased (P < 0.05) the expression of the cytoplasmic precursor (3-fold of the control) and nuclear active forms (1.5-fold of the control) of SREBP2. We conclude that the hypocholesterolemic effects of GG consumption are related to a reduction in hepatic free cholesterol concentration and associated increases in nuclear active SREBP2 expression and hepatic LDLr abundance.

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