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Dietary Fat and Cholesterol Effects on Cholesterol Metabolism in CBA/J and C57BR/cdJ Mice¹

Department of Food and Nutrition, Iowa State University, Ames, IA 50011

The aim of this study was to determine how small differences in dietary fats affect cholesterol metabolism in mice hypo- (CBA/J) and hyperresponsive (C57BR/cdJ) to diet-induced hypercholesterolemia. Six-wk-old male mice were fed either a diet corresponding to the U.S. average gross composition (US74, 40% of total energy as fat, 347 mg cholesterol/1000 Kcal, P/S = 0.24) or a modified-fat diet (30% of total energy as fat, 46 mg cholesterol/1000 Kcal, P/S = 0.91). After 8 wk of feeding, neither strain had developed hypercholesterolemia. CBA/J mice had higher concentrations of serum total and high-density lipoprotein (HDL) cholesterol and a higher esterified-to-free cholesterol ratio than did C57BR/cdJ mice. CBA/J mice maintained a constant serum cholesterol concentration mainly by adjusting the hepatic hydroxymethylglutaryl coenzyme A reductase (HMGR) activity, whereas C57BR/cdJ mice did so by changing the fecal excretion of cholesterol. Compared to the modified-fat diet, the US74 diet caused an increase in the ratio of total to HDL serum cholesterol, liver microsomal free cholesterol, fecal cholesterol and hepatic microsomal cholesterol 7-hydroxylase activity and a decrease in hepatic microsomal HMGR activity. We conclude that the metabolic responses to small differences in dietary fat are different in CBA/J and C57BR/cdJ mice.

KEY WORDS: • fat • saturated fat • linoleate • genetics • hydroxymethylglutaryl coenzyme A reductase • cholesterol 7-hydroxylase

¹ Journal Paper No. J-13005 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa. Project No. 2571, a contributing project to North Central Regional Research Project NC-167.

² Present address: Department of Internal Medicine, Division of Endocrinology, Old Medical School, Box 135, University of Virginia, Charlottesville, VA 22908.

³ To whom reprint requests should be addressed.

Manuscript received 22 March 1988. Revision accepted 4 November 1988.

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