Journal of Lipid Research, Vol. 20, 175-182, February 1979
Copyright © 1979 by Lipid Research, Inc.

Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed swine

B. M. Wolfe and D. M. Grace

University Hospital and Departments of Medicine and Surgery, University of Western Ontario, London, Ontario, Canada

The effects of conventional doses of two synthetic contraceptive steroids on the concentration and rate of secretion of plasma triglycerides from the splanchnic region were investigated. Studies were undertaken in miniature swine under steady state conditions produced by prolonged constant hypercaloric intravenous infusions of glucose. The steroids, alone or in combination, were administered with the high carbohydrate diet for at least 2 weeks prior to study of splanchnic metabolism and were also infused intravenously during the studies. Splanchnic triglyceride secretion was determined from measurements of plasma flow and transsplanchnic radiochemical gradients of plasma triglycerides. Compared with studies in the untreated animal, norethindrone acetate significantly reduced the arterial concentration (1.1 ± 0.1 vs. 0.7 ± 0.1 mM) and rate of splanchnic secretion of plasma triglyceride fatty acids (2.0 ± 0.4 vs. 0.8 ± 0.1 µmol/min·kg body wt^0.75) and decreased the percent of free fatty acids entering the splanchnic region that was converted to plasma triglycerides (22 ± 5 vs. 13 ± 3%, P < 0.05). Ethynylestradiol, in the dose employed, had no significant effect on these variables; however, ethynylestradiol and norethindrone acetate together gave responses similar to norethindrone acetate alone. When the glucose was given intraduodenally vs. intravenously, values for splanchnic metabolism of triglycerides were unchanged. The hypolipemic effect of norethindrone acetate in glucose-fed swine was attributable to inhibition of hepatic triglyceride secretion.—Wolfe, B. M., and D. M. Grace. Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed swine.

Supplementary key words free fatty acids • glycogen • liver • metabolism • miniature swine • very low density lipoprotein

Submitted on September 7, 1977
Revised on April 21, 1978
Accepted on August 2, 1978

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