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Potency of Polyunsaturated and Saturated Fats as Short-Term Inhibitors of Hepatic Lipogenesis in Rats¹

Graduate Program of Nutrition, University of Minnesota, St. Paul, MN 55108 ^* Unit of Reproduction and Growth Physiology, The Upjohn Company, Kalamazoo, MI 49001

Three dietary studies using male Sprague-Dawley rats conditioned to meal-eat a high glucose, fat-free diet and one in vitro study with isolated rat hepatocytes were designed to examine the hypothesis that polyunsaturated fats (i.e., safflower oil or linoleate) are more potent acute inhibitors of liver fatty acid synthesis than are saturated fats (i.e., beef tallow or palmitate). Fat in the first in vivo study was administered via intubation (1500 mg/rat) whereas in the second and third in vivo studies fat was added to the meal in amounts of 50, 100, 250 or 500 mg/g fat-free diet. When the rats were in a postprandial condition, significant suppression of hepatic lipogenesis required the meal to contain 38% of its energy as fat (i.e., 250 mg/g fat-free diet). At this level of fat, safflower oil was more inhibitory than beef tallow (p < 0.05). The inhibition constant (K_i) for palmitate inhibition of fatty acid synthesis by isolated hepatocytes was fourfold greater than linoleate's K_i (fatty acid/albumin ratio of 1.4/1). When fat constituted 50% of the ingested energy, beef tallow was equivalent to safflower oil as an inhibitor of lipogenesis. Although a single meal containing 50 mg safflower oil/g fat-free diet did not decrease fatty acid synthesis, it effectively delayed the induction of lipogenesis during the first 30 min of ingestion of a second meal. These data indicate that the adaptive decrease in lipogenic enzymes attributed to polyunsaturated fats extends to short-term regulatory mechanisms.

KEY WORDS: • lipogenesis • lipids • liver • rats • hepatocytes

¹ This work was conducted at the University of Minnesota as part of National Institutes of Health grant R01-HL-23159.

Manuscript received 24 May 1989. Revision accepted 19 January 1990.