Digestion of triglyceride in the intestine results in the production of 2-monoglyceride and fatty acid. Phosphatidylcholine is hydrolyzed in the lumen to form lysophosphatidylcholine before its absorption. These digestion products are absorbed by the enterocytes through simple diffusion. In contrast, cholesterol absorption seems specific and is energy dependent. After entry into the enterocytes, these lipid digestion products migrate to the endoplasmic reticulum. Both fatty acid-binding protein and sterol carrier protein may be involved in the intracellular transport of fatty acid and cholesterol, respectively. Through predominantly the monoglyceride pathway, monoglycerides and fatty acids are resynthesized to form triglyceride in the endoplasmic reticulum. The lipid droplets, coated with cholesterol, phospholipid, and apolipoproteins, are then further processed in the Golgi apparatus before being released by the enterocytes through exocytosis. As yet, little is known of the factors regulating the formation and release of these chylomicrons by the enterocytes. Although apolipoprotein B is a prerequisite for the formation of chylomicrons, the question of whether its supply is rate limiting for chylomicron formation remains to be demonstrated. Other factors that may play a role in chylomicron formation are luminal phospholipid supply, Ca2+, and microtubules. Chylomicrons and very low-density lipoproteins are probably produced by the enterocytes via different pathways. For example, Pluronic L-81, a hydrophobic surfactant, affects only chylomicron formation and has little effect on very low-density lipoprotein production. The movement of chylomicrons from the intercellular space through the basement membrane to the lamina propria is not fully understood. Once inside the lamina propria, the movement of chylomicrons is probably by diffusion and is greatly facilitated by interstitial hydration; thus the lymphogogic effect of fat absorption may serve an important function for the transfer of chylomicrons from the enterocytes to the lacteal.

Lymph fistula rats were used to determine the acute effects of the hydrophobic surfactant, Pluronic L-81, on lipid transport by the small bowel. Animals were infused intraduodenally with a lipid emulsion containing [3H]triolein and Pluronic L-81, and the rate of intestinal transport of absorbed lipid into lymph was studied using liquid scintillation spectrometry. With this technique, various dose levels of Pluronic L-81 were analyzed for a possible inhibitory effect on lipid transport. Also, the rate at which this agent produced inhibition of intestinal lipid transport was determined. Results were correlated with electron microscopic studies of jejunal enterocytes and lipoprotein particles recovered in intestinal lymph. Infusion of Pluronic L-81 at a rate of 0.25 mg/h had no effect, but infusion at 0.5 and 1 mg/h produced a dramatic reduction in lipid transport by the small bowel. The rate of inhibition of lymphatic lipid output was rapid, with a t1/2 of 69 min for the 0.5 mg/h dose and 35 min for the 1 mg/h dose. This inhibition of lipid transport was associated with marked mucosal accumulation of lipid as demonstrated by radiochemical and morphological data. By electron microscopic analysis, only very low-density lipoprotein-sized particles were transported into lymph by enterocytes exposed to an effective dose of Pluronic L-81. It is concluded that small amounts of Pluronic L-81 produce a striking inhibition in the intracellular transport of chylomicron-sized particles, thereby blocking secretion of chylomicrons by the enterocytes. Furthermore, this action is very rapidly produced by effective doses of this agent.

The effect of chronic feeding (3-4 wk) of the hydrophobic surfactant, Pluronic L-81, on the lymphatic transport of triglyceride and cholesterol was studied in rats with thoracic duct fistula. A lipid emulsion containing [3H]triolein (13.3 mM), [14C]cholesterol (2.6 mM), phosphatidylcholine (2.9 mM), sodium taurocholate (19 mM), with 0.17 mg/ml (experimental) or without Pluronic L-81 (L-81) added (control) was infused at the rate of 3 ml/h. Lymph triglyceride and cholesterol outputs were greatly impaired in the experimental rats compared to the control rats. The phospholipid output compared to the control was also reduced but to a lesser extent in the experimental rats. Comparable recovery of radioactive 3H-labeled lipid and [14C]cholesterol from the intestinal lumen of control and experimental rats showed that digestion and absorption were not impaired in the experimental rats. The distribution of mucosal 3H radioactivity in various lipid fractions showed no impairment in reesterification. The greatly depressed lymphatic lipid transport was associated with marked accumulation of absorbed lipid in enterocytes, suggesting that Pluronic L-81 interferes with lipoprotein assembly and/or exit of lipoproteins from the mucosal cells. The animals fed chronically for 4-6 wk regained their ability to transport lipid 24 h after termination of L-81 feeding. The effect of this agent, therefore, is readily reversible.

This document represents a consensus statement dealing with optimum patient care in a significant clinical area. The statement has been prepared by the Patient Care Committee of the American Gastroenterological Association with the advice of other experts and with peer review. As with all such guidelines, this should be interpreted in a nondogmatic manner, so as not to exclude other therapies or opinions in any particular situation. Based on present knowledge, limited at times, future modifications or other changes in this statement may be necessary.

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