Inhibition of carnitine palmitoyltransferase in the rat small intestine reduces export of triacylglycerol into the lymph.
Following digestion of dietary triacylglycerol (TAG), intestinal epithelial cells absorb fatty acids and monoacylglycerols that are resynthesized into TAG by enzymes located on the endoplasmic reticulum (ER). A study in rat liver (Abo-Hashema, K. A., M. H. Cake, G. W. Power, and D. J. Clarke. 1999. Evidence for TAG synthesis in the lumen of microsomes via a lipolysis-esterification pathway involving carnitine acyltransferases. J. Biol. Chem. 274: 35577-35582) showed that there is a carnitine-dependent ER lumenal synthesis of TAG. We wanted to test the hypothesis that a similar pathway was present in rat intestine by utilizing etomoxir, a specific inhibitor of carnitine palmitoyltransferase (CPT). Intraduodenal infusion of etomoxir inhibited CPT activity in the ER by 69%. Etomoxir did not affect either the uptake of intraduodenally infused [3H]glyceryltrioleate by the intestinal mucosa or the production of mucosal [3H]TAG, excluding the possibility that etomoxir interfered with TAG absorption or synthesis. Etomoxir did not inhibit protein synthesis, glucose, cholesterol or palmitate absorption or metabolism, or ATP concentrations. Etomoxir substantially (74%) diminished lymph TAG output from intralumenally infused glyceryltrioleate. In conclusion, these data strongly support the hypothesis that an ER CPT system exists and is necessary for processing dietary TAG into chylomicrons. The significant reduction in lymphatic output of chylomicron TAG on etomoxir treatment suggests that the major source of chylomicron TAG is a diacylglyceroltransferase on the lumenal surface of the ER.
Washington
LaTonya
L
Department of Pharmacology, Department of Medicine, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38104, USA.
Cook
George A
GA
Mansbach
Charles M
CM
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000201:enzymology*; D008099:Liver / Q000378:metabolism; D008196:Lymph / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D014280:Triglycerides; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir