Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats.
The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, we have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of [14C]linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that (a) colchicine causes significant changes in enterocyte ultrastructure and (b) colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte.
D000818:Animals; D002250:Carbon Radioisotopes; D003078:Colchicine / Q000494:pharmacology*; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D007583:Jejunum / Q000648:ultrastructure; D019787:Linoleic Acid; D008041:Linoleic Acids; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D008041:Linoleic Acids; D008074:Lipoproteins; D014280:Triglycerides; D019787:Linoleic Acid; D003078:Colchicine