Chylomicron and palmitate metabolism by perfused hearts from diabetic mice

Hydrolysis of triacylglycerols (TG) in circulating chylomicrons by endothelium-bound lipoprotein lipase (LPL) provides a source of fatty acids (FA) for cardiac metabolism. The effect of diabetes on the metabolism of chylomicrons by perfused mouse hearts was investigated with db/db (type 2) and streptozotocin (STZ)-treated (type 1) diabetic mice. Endothelium-bound heparin-releasable LPL activity was unchanged in both type 1 and type 2 diabetic hearts. The metabolism of LPL-derived FA was examined by perfusing hearts with chylomicrons containing radiolabeled TG and by measuring 3H2O accumulation in the perfusate (oxidation) and incorporation of radioactivity into tissue TG (esterification). Rates of LPL-derived FA oxidation and esterification were increased 2.3-fold and 1.7-fold in db/db hearts. Similarly, LPL-derived FA oxidation and esterification were increased 3.4-fold and 2.5-fold, respectively, in perfused hearts from STZ-treated mice. The oxidation and esterification of [3H]palmitate complexed to albumin were also increased in type 1 and type 2 diabetic hearts. Therefore, diabetes may not influence the supply of LPL-derived FA, but total FA utilization (oxidation and esterification) was enhanced.

Fatty acid metabolism in hepatocytes cultured with hypolipidaemic drugs. Role of carnitine

The direct effects of clofibrate analogues on carnitine acyltransferase activities and fatty acid metabolism were studied in cultured hepatocytes. Rat hepatocytes cultured with bezafibrate or ciprofibrate (0.1-10 micrograms/ml) for 48 h had increased activities of carnitine acetyltransferase (CAT; 4-6-fold) and carnitine palmitoyltransferase (CPT; 12-34%). The increase in CAT was higher in hepatocytes from the periportal zone (440%) of rat liver compared with cells from the perivenous zone (266%). In human hepatocytes, in contrast with rat, the fibrates did not cause a marked increase in CAT activity. The effects of fibrates on palmitate metabolism were dependent on the carnitine status. In the presence of exogenous carnitine (1 mM), rat hepatocytes cultured with bezafibrate had higher rates of total palmitate metabolism (29-34%) without increased partitioning of palmitate towards beta-oxidation, relative to control cultures. At low endogenous carnitine concentrations, cells cultured with bezafibrate had a greater increase in palmitate metabolism, esterification and cellular accumulation of triacylglycerol compared with the corresponding increases in the presence of carnitine. The changes in palmitate metabolism at either high or low carnitine concentrations were small in comparison with the changes in CAT activity. It is concluded that the increase in hepatic carnitine that occurs in vivo after fibrate feeding probably plays the major role in the changes in partitioning of fatty acid between beta-oxidation and esterification.