Intestinal lipoprotein formation: effect of cholchicine

The possibility that microtubules might be involved in intestinal lipoprotein formation or secretion was studied by determining the effect of colchicine, a known microtubule inhibitor, on intestinal lipid absorption. The effect of colchicine (0.5 mg per 100 g) in the lymphatic absorption of [14C]oleic acid was studied in rats with indwelling mesenteric lymph cannulas. Colchicine-treated animals showed a marked delay as well as a decrease in the lympatic absorption of [14C]oleic acid. Chylomicrons from colchicine-treated animals showed no difference in apoprotein content when examined on sodium dodecyl sulfate polyacrylamide gels. Micellar lipid absorption was next studied from in situ jejunal loops in animals pretreated with colchicine. Colchicine administration was associated with a 3-fold increase in residual mucosal lipid when compared with controls. Thin layer chromatography of residual lipid demonstrated that residual lipid was largely present as triglyceride, suggesting that the impairment in lipid transport induced by colchicine was at a site distal to triglyceride resynthesis. Electron microscopic examination of intestine from colchicine-treated animals revealed that most residual lipid was present within the endoplasmic reticulum and Golgi in numerous particles the size of chylomicrons (0.2 to 0.4 mu). These results suggest that the impairment in lipid transport induced by colchicine is distal and, in part, may represent an "exit block". These results suggest a possible role for microtubules in intestinal lipid transport. However, further studies are required to demonstrate directly the participation of microtubules in chylomicron secretion.