Catabolism of chylomicron triacylglycerol and cholesteryl ester in genetically obese rats

Abstract

The catabolism of chylomicrons was investigated in genetically obese rats and their nonobese littermates, and was compared with catabolism in older Sprague–Dawley rats with body weights similar to the obese rats and their younger controls. Labeled thoracic-duct lymph was collected from donor rats and the catabolism of the labeled chylomicrons was studied after a single intravenous injection or during steady intravenous infusion in unanesthetized, nonfasting, recipient rats. In the genetically obese rats clearances from the plasma of chylomicron triacylglycerol and cholesteryl ester were less than in their nonobese littermates. Fractional clearance rates were reduced for both triacylglycerol and cholesteryl ester but triacylglycerol turnover rate (mg min−1) was greater than controls. Chylomicron triacylglycerol clearance was more efficient than cholesteryl ester clearance so that radioactivity remaining in the plasma was relatively depleted in triacylglycerol. The large-bodied old Sprague–Dawley rats showed no reduction in clearance of chylomicron radioactivity in comparison with younger controls.These results suggest that hyperlipidemia in genetically obese rats may be due in part to an accumulation of chylomicron remnants in the plasma. Flotation characteristics of plasma lipoproteins in the obese rats were consistent with this interpretation. However, separate experiments showed that genetically obese, fasting rats also accumulated more triacylglycerol in the plasma after injection of Triton WR 1339. The enlarged plasma triacylglycerol pool appears to derive from a mixture of hepatic and intestinal triacylglycerol-rich lipoproteins which, together, overload their common removal mechanism. Addition of cholesterol to the diets of the obese rats exacerbated their hyperlipemia and hepatic steatosis whereas their nonobese littermates and the large-bodied Sprague–Dawley rats were unaffected.

Keywords

• Zucker rats
• fractional catabolic rate
• turnover