Effect of chloroquine on intestinal lipid metabolism.
Most studies that have quantitated recovery of infused lipid in the intestinal mucosa and mesenteric lymph have only been able to recapture 50-75%. One possibility is that the missing lipid enters a triacylglycerol (TG) storage pool in the enterocyte and is hydrolyzed by lysosomal lipase, and the free fatty acid released is transported by the portal vein. This postulate was tested by comparing glyceryl trioleate (TO)-infused rats pretreated with the lysosomotropic drug, chloroquine (6.3 mg.kg-1.h-1) with saline controls. Chloroquine increased mucosal TG from 94 +/- 6 to 128 +/- 8 mumol. Additionally, the specific activity of the mucosal TG relative to the infused [3H]TO was reduced in the treated rats. The mucosal TG increase was not due to impaired TG output, which remained the same as controls. We conclude that the TG in the acid lipase-sensitive pool derives most of its glyceride-glycerol from endogenous sources. Furthermore, the increment in mucosal TG caused by chloroquine is not enough to explain the majority of the acyl groups unaccounted for in the mucosa and lymph after a TG infusion. For these a direct passage of acyl groups through the enterocyte is postulated.
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
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Mansbach
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Arnold
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Garrett
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D002738:Chloroquine / Q000494:pharmacology*; D002914:Chylomicrons / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism; D008196:Lymph / Q000378:metabolism; D008297:Male; D051381:Rats; D014018:Tissue Distribution; D014280:Triglycerides / Q000378:metabolism; D014304:Triolein / Q000378:metabolism / Q000493:pharmacokinetics; D014316:Tritium
D002250:Carbon Radioisotopes; D002914:Chylomicrons; D014280:Triglycerides; D014316:Tritium; D014304:Triolein; D002738:Chloroquine