Effect of hydrophobic surfactant (Pluronic L-81) on lymphatic lipid transport in the rat

Abstract

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.

Intestinal alkaline phosphatase release is not associated with chylomicron formation

“…2) indicates that the amount of Pluronic L-81 used in our experiment was clearly sufficient to block the formation of chylomicrons and thus prevent the increase in lymphatic triacylglycerol output during fat absorption. These data support numerous other reports of the effects of Pluronic L-81 on chylomicron formation (21,(24)(25)(26)(27).…”

“…Chylomicron formation was inhibited by the compound Pluronic L-81 (21,(24)(25)(26)(27), and yet, it is evident from Figs. 3 and 4 that Pluronic L-81 did not inhibit increase in lymphatic alkaline phosphatase secretion induced by active lipid absorption.…”

“…Once inside the intestinal cells, triacylglycerols are synthesized from the fatty acids and 2-monoacylglycerols and transported to the lymph via chylomicrons. Because Pluronic L-81 blocks chylomicron formation and secretion, but does not interfere with the uptake and the reesterification of monoacylglycerols and fatty acids to form triacylglycerols (21,(24)(25)(26)(27), we determined whether the stimulation of lymphatic alkaline phosphatase secretion by lipid absorption is mediated by the presence of intracellular lipid or by the formation and secretion of chylomicrons. As shown in Fig.…”

“…Olestra, a fat substitute comprising sucrose esterified with 6-8 fatty acids (16)(17)(18), is currently commercialized in food products. In addition, we used the hydrophobic surfactant Pluronic L-81, because it blocks the formation of chylomicrons by blocking trafficking of prechylomicrons from endoplasmic reticulum to Golgi apparatus without altering reesterification of the digestion products (21,(24)(25)(26)(27).…”

Pluronic L81 ameliorates diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein

“…Chronic feeding of rats with L-81 greatly reduced the lymphatic lipid transport from their intestine, without affecting the digestion and absorption of lipid into enterocytes. The absorbed lipid was however accumulated in the enterocytes, suggesting that L-81 interferes with lipoprotein assembly and/or exit of lipoproteins from the mucosal cells [4] . L-81 inhibits chylomicron formation but not very low density lipoprotein (VLDL) assembly in the intestine [5] .…”