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Inhibition of Triiodothyronine's Induction of Rat Liver Lipogenic Enzymes by Dietary Fat¹

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

The objective of these studies was to demonstrate that the reduction in lipogenic enzymes caused by ingestion of dietary polyunsaturated fat can in part be attributed to an inhibition of triiodothyronine's induction of hepatic lipogenic enzymes. A 3 x 4 factorial design was employed to examine the effect of diets containing no fat, beef tallow or safflower oil on the triiodothyronine-mediated (0, 2, 4 or 8 µg/100 g injected daily intraperitoneally) induction of rat liver lipogenic enzymes. Triiodothyronine (T₃) administration induced (p < 0.05) the activity of malic enzyme, fatty acid synthase and glucose-6-phosphate dehydrogenase in a dose-dependent manner. Malic enzyme activity was increased five- to sevenfold by 8 µg T₃/100 g daily. Fatty acid synthase activity at the 8 µg dose had increased two- to threefold whereas glucose-6-phosphate dehydrogenase activity was elevated only 15–35%. Beef tallow and safflower oil supplementation of the high glucose, fat-free diet significantly reduced the T₃ induction of all the enzymes. Safflower oil was more effective than tallow as a repressor of T₃ action. The effect of dietary fat, particularly safflower oil, was to increase the amount of T₃ required to induce the activity of lipogenic enzymes. In a second study, with a 2 x 2 factorial design, daily injection of 15 µg T₃/100 g was found to overcome the safflower oil inhibition of lipogenic enzymes. These data support the hypothesis that polyunsaturated fats uniquely suppress the gene expression of lipogenic enzymes by functioning as competitive inhibitors of T₃ action, possibly at the nuclear receptor level.

KEY WORDS: • lipogenesis • polyunsaturated fat • thyroxine • rats

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.