Effect of Acipimox on Plasma Lipids and Glucose/Insulin in Pregnant Rats

Abstract

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (IV) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance. The enhanced lipolytic activity present during late gestation gives rise to an elevation in plasma free fatty acids (FFA) and triglycerides (TG), both in women and rats [1][2][3]. Some tissues use fatty acids as fuel, sparing glucose for the fast-growing fetus and those maternal tissues that can only use glucose as fuel energy [4]. The mechanisms involved in this elevated lipolytic activity are uncertain, but the rising levels of placental lactogen and the insulin resistance during late pregnancy seem to play a relevant role [5][6][7].The enhanced availability of FFA to the liver seems to contribute to the increased production of TG by this organ [8] and therefore to the development of maternal hypertriglyceridemia. Exaggerated increment of TG in maternal circulation may be involved in some of the pregnancy-induced complications, including eclampsia [9] and insulin resistance that would cause the development of gestational diabetes [7], 2 of the most common pregnancy-induced complications. Therefore, decreasing the hypertriglyceridemia of late pregnancy may be of therapeutic use. Nevertheless, this therapeutic approach may not be risk free for the fetus, becaus...

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