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P Nevin

Publications and source records attributed to P Nevin.

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Intracellular movement of triacylglycerols in the intestine.

The intestine can vary its triacylglycerol output rate depending on differing physiological conditions. The rate-limiting step in the complex process from fatty acid and monoacylglycerol entry to triacylglycerol export is unknown but suggested to be the transport of triacylglycerol from the endoplasmic reticulum to the Golgi. The present studies were carried out to test this hypothesis. The conversion rate of absorbed fatty acid to mucosal triacylglycerol was studied in rats infused intraduodenally with trioleoylglycerol, 135 micromol/h, for 6 h followed by [3H]oleate. In 30 sec, 79% of the mucosal 3H-labeled fatty acid was esterified to [3H]triacylglycerol. The increase in the 3H specific activity of triacylglycerol in the endoplasmic reticulum and Golgi was studied in similarly prepared rats except that the radio-label was [3H]trioleoylglycerol. The endoplasmic reticulum triacylglycerol specific activity was always less than that of the Golgi with a steady state not reached until 60 min of [3H]trioleoylglycerol infusion. The steady state of [3H]triacylglycerol in the lymph was not reached until 70 min of infusion. We conclude that the data are consistent with the rate-limiting step in intestinal triacylglycerol export being the movement of triacylglycerol from the endoplasmic reticulum to the Golgi as the conversion of absorbed fatty acid to triacylglycerol is rapid and the movement of triacylglycerol from the Golgi to the lymph is rapid as well.

Animals↗

Intestinal triacylglycerol storage pool size changes under differing physiological conditions.

The intestinal mucosal triacylglycerol storage pool consists of triacylglycerol that is predominantly transported from the intestine via the portal vein rather than in chylomicrons (Am. J. Physiol. 1991. 261: G530-G538). Here we examined the size of the storage pool under varying physiological conditions. Four groups of rats were infused intraduodenally for 4 h. Group A was fasted; group B was infused with trioleoylglycerol, 135 mumol/h; group C was infused with trioleoylglycerol, 135 mumol/h plus phosphatidylcholine, 9 mumol/h; and group D was bile-diverted and infused with trioleoylglycerol, 135 mumol/h. The amount of triacylglycerol in the mucosa increased from groups A to D (A > B > C > D) but the storage pool triacylglycerol was least in groups A and C and greatest in groups B and D. The percentage of trioleoylglycerol in mucosal triacylglycerol was greater in groups B and D than in group A and greater in all groups than the percentage of oleate in the total fatty acids. We conclude that the triacylglycerol storage pool size varies inversely with the efficiency of lymphatic lipid output, which is greatest in rats infused with trioleoylglycerol plus phosphatidylcholine (group C) and least in bile-diverted rats infused with trioleoylglycerol (group D).

Analysis of Variance↗

Effect of brefeldin A on lymphatic triacylglycerol transport in the rat.

Brefeldin A (BFA) has been shown in in vitro studies to either collapse the Golgi into the endoplasmic reticulum (ER) or the peripheral organelles into the trans-Golgi network. Our goal was to determine the effect of BFA on intestinal lipid transport, since the Golgi is thought to play an important role in this process and simultaneously establish the effectiveness of BFA in an in vivo system. We infused rats intraduodenally with glyceryl tri-[3H]oleate at 135 mumol/h for 15 h and included BFA, 750 micrograms/h, during hours 4-7 of infusion. Mass and lipid disintegrations per minute output into the lymph fell to 9% of input rates at 8 h of infusion and returned to steady-state values at 12 h of infusion. Both chylomicron and very low-density lipoprotein output were severely affected by the BFA. Electron microscopy showed that the Golgi was collapsed into the ER. Mucosal triacylglycerol (TG) mass and disintegrations per minute were increased at 7 h of infusion in BFA infused rats vs. controls in the proximal half of the intestine. Lipid absorption, lipase activity, and mucosal TG synthesis were normal in the BFA-treated rats. We conclude that BFA works in vivo and in the intestine collapses the Golgi into the ER. As a consequence, lymphatic TG transport was severely affected.

Animals↗