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Effect of Dietary Cholesterol on Hepatic Lipogenesis and Plasma Insulin and Free Fatty Acid Levels in Rats¹

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824

In order to further investigate the metabolic alterations in the liver of cholesterol-fed rats, the following parameters were determined: (a) the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, citrate cleavage enzyme, acetyl CoA carboxylase, and fatty acid synthetase; (b) the rate of hepatic fatty acid synthesis in vivo or in vitro; and (c) the concentration of immunoreactive insulin, free fatty acids, and glucose in the plasma. The experimental diets usually contained 1.5% cholesterol and 0.5% cholic acid. Cholesterol feeding resulted in a three- to fourfold decrease in the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, and citrate cleavage enzyme and up to a two-fold decrease in the activities of acetyl CoA carboxylase and fatty acid synthetase. The rate of fatty acid synthesis was not significantly decreased when rats were fed the cholesterol-supplemented diets for only 2 to 4 weeks, despite marked decreases in the activities of the lipogenic enzymes. But when cholesterol feeding was continued for periods longer than 5 weeks, there was a significant decrease in the rate of fatty acid synthesis in the liver. Cholesterol feeding decreased the levels of circulating insulin and elevated plasma free fatty acid levels. Plasma glucose levels were not significantly changed. Cholesterol feeding can result in a wide range of metabolic alterations. These metabolic alterations may have some impact on the development of hypercholesterolemic-related metabolic disorders.

KEY WORDS: • cholesterol feeding • liver enzymes • lipogenesis • insulin • free fatty acids

¹ Supported in part by Public Health Service Grant no. HL 14677 from the Heart and Lung Institute. Michigan Agriculture Experiment Station Journal Article no. 7135.

² Present address: Human Nutrition Program, M5170, School of Public Health, University of Michigan, Ann Arbor, Mich. 48104.

Manuscript received 10 February 1975.