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Biochemical and Molecular Action of Nutrients

Corn Fiber Oil Lowers Plasma Cholesterol by Altering Hepatic Cholesterol Metabolism and Up-Regulating LDL Receptors in Guinea Pigs¹

Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269 and ^* Monsanto Company, St. Louis, MO 63167

²To whom correspondence should be addressed. E-mail: maria-luz.fernandez{at}uconn.edu.

To evaluate some of the mechanisms involved in the hypocholesterolemic effects of corn fiber oil (CFO), male Hartley guinea pigs were fed diets containing increasing doses of CFO [0 (control), 5, 10 or 15 g/100 g]. Total fat was adjusted to 15 g/100 g in all diets with regular corn oil. Diets contained 0.25 g/100 g cholesterol. A positive control group (LC) with low dietary cholesterol (0.04 g/100 g) was also included. Plasma LDL cholesterol concentrations were 32, 55 and 57% (P < 0.0005) lower with increasing doses of CFO. Compared with controls, intake of CFO resulted in 27–32% lower hepatic microsomal cholesterol (P < 0.0001), the regulatory pool of LDL receptor (LDL-R) expression. CFO intake resulted in favorable plasma and hepatic cholesterol concentrations, similar to those in guinea pigs fed the LC diet. Hepatic cholesterol 7-hydroxylase (CYP7) activity was 88% higher in guinea pigs fed the two higher dosages of CFO (P < 0.05). In parallel, CYP7 mRNA abundance was 88% higher in guinea pigs fed all three CFO diets. CFO treatment also induced hepatic LDLR mRNA by 66–150% with significant differences at the highest CFO dose. These results suggest that CFO, as a result of decreased bile acid absorption, increased mRNA abundance and activity of CYP7. Because hepatic cholesterol is the substrate for CYP7, a lowering of cholesterol concentrations in the total and microsomal pools was observed. As a response to the depleted microsomal free cholesterol pool, the LDL receptor was up-regulated, drawing more cholesterol from plasma, thus leading to the observed decrease in plasma LDL cholesterol concentrations.

KEY WORDS: • corn fiber oil • microsomal cholesterol • LDL receptor • cholesterol 7-hydroxylase • guinea pigs

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