Cm. Mansbach et P. Nevin, EFFECT OF BREFELDIN-A ON LYMPHATIC TRIACYLGLYCEROL TRANSPORT IN THE RAT, The American journal of physiology, 266(2), 1994, pp. 70000292-70000302
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.