The role of the liver and of extrahepatic tissues in the transport and metabolism of fatty acids and triglycerides in the dog

SUMMARY Labeled free fatty acids (FFA) and chylomicron triglycerides were injected intravenously into intact and hepatectomized dogs. Measurements were then made of the rate of their removal from the circulation, conversion to other circulating lipids, oxidation, and distribution in certain tissues. Hepatectomy reduced the rate of removal of FFA from the circulation moderately, but almost abolished the appearance of radioactivity in circulating triglycerides, indicating that the liver is the chief site of conversion of plasma FFA to plasma triglycerides. Experiments in dogs with thoracic duct fistulae showed that these triglycerides enter the circulation through the hepatic sinusoids. In hepatectomized animals a small quantity of triglycerides continues to enter the blood stream, probably from the intestinal mucosa by way of the thoracic duct, and possibly from other sites as well. Hepatectomy or temporary exclusion of the liver from the circulation reduced the rate of removal of chylomicron triglycerides variably. Hydrolysis to form circulating FFA occurred as in intact dogs. Most of the triglycerides removed from the circulation of hepatectomized dogs appeared to enter adipose tissue. Evidence was obtained that these triglycerides were hydrolyzed prior to entrance of their constituent fatty acids into adipose tissue cells. chylomicron triglycerides and FFA' bound to albumin have been shown to have rapid turnover rates in the blood (l). The liver is known to play an important role in their removal from the circulation. Bragdon and Gordon (2) injected fasting rats intravenously with albumin-bound palmitic a~id-1-C'~ and with chylomicrons obtained from the thoracic duct lymph of rats fed palmitic a~id-1-C'~. Ten minutes after the injection they found that 12% and 21%, respectively, of the radioactivity cleared from the blood was present in liver lipids. Removal of these lipid moieties from the circulation by the liver has also been demonstrated by measurement of portal-hepatic venous differences (3, 4, 5). In the present investigation we studied the metabolism of chylomicron t(rig1ycerides and FFA in intact and hepatectomized dogs. The results obtained provide further information regarding the role of the liver, and emphasize the importance of extrahepatic tissues in the transport and metabolism of these constituents.