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Dietary Fat Saturation and Chain Length Modulate Guinea Pig Hepatic Cholesterol Metabolism^1,2,

Department of Nutritional Sciences and Interdisciplinary Nutritional Sciences Program, University of Arizona, Tucson, AZ 85721

The effects of dietary fat saturation and saturated fatty acid composition on plasma lipoprotein concentrations and hepatic cholesterol metabolism were investigated in guinea pigs. Animals were fed semipurified diets containing 15 g fat/100 g diet, as palm kernel, palm oil, beef tallow, lard, olive oil or corn oil. Plasma lipoprotein concentrations were significantly altered by the type of dietary fat. The LDL cholesterol concentration was highest in animals fed the diet with palm kernel and lowest in animals fed the diet with corn oil, whereas HDL cholesterol was lowest in beef tallow-fed guinea pigs (P < 0.01). Hepatic cholesteryl ester concentrations were 100% higher in animals fed diets containing polyunsaturated corn oil and monounsaturated olive oil compared with animals fed any of the saturated fat diets (P < 0.01). Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity varied in the different dietary fat groups independent of hepatic cholesterol pools or plasma LDL concentrations. In contrast, hepatic acyl-CoA: cholesterol acyltransferase (ACAT) activity was significantly correlated with plasma LDL cholesterol across all dietary groups (r = 0.63, P < 0.001). These data demonstrate that regulation of hepatic HMG-CoA reductase activity is relatively independent of changes in plasma lipoprotein levels, whereas hepatic ACAT activity exhibits a positive correlation with plasma LDL cholesterol concentrations.

KEY WORDS: • hepatic cholesterol • dietary fat saturation • hepatic HMG-CoA reductase • guinea pigs • acyl-CoA:cholesterol acyltransferase

¹ Supported by a grant-in-aid from the American Heart Association, Arizona Affiliate, a grant-in-aid from the Cattlemen's Beef Promotion and Research Board administered in cooperation with the Beef Industry Council, and funds provided by the University of Arizona Agricultural Experimental Station.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 10 May 1993. Revision accepted 25 October 1993.

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