EFFECT OF BREFELDIN-A ON LYMPHATIC TRIACYLGLYCEROL TRANSPORT IN THE RAT

Brefeldin A (BFA) has been shown in in vitro studies to either collaps e the Golgi into the endoplasmic reticulum (ER) or the peripheral orga nelles into the trans-Golgi network. Our goal was to determine the eff ect of BFA on intestinal lipid transport, since the Golgi is thought t o play an important role in this process and simultaneously establish the effectiveness of BFA in an in vivo system. We infused rats intradu odenally with glyceryl tri-[H-3]oleate at 135 mu mol/h for 15 h and in cluded BFA, 750 mu g/h, during hours 4-7 of infusion, Mass and lipid d isintegrations per minute output into the lymph fell to 9% of input ra tes at 8 h of infusion and returned to steady-state values at 12 h of infusion. Both chylomicron and very low-density lipoprotein output wer e severely affected by the BFA. Electron microscopy showed that the Go lgi was collapsed into the ER. Mucosal triacylglycerol (TG) mass and d isintegrations per minute were increased at 7 h of infusion in BFA inf used rats vs. controls in the proximal half of the intestine. Lipid ab sorption, lipase activity, and mucosal TG synthesis were normal in the BFA-treated rats. We conclude that BFA works in vivo and in the intes tine collapses the Golgi into the ER. As a consequence, lymphatic TG t ransport was severely affected.