Catabolic defect of triglyceride is associated with abnormal very-low-density lipoprotein in experimental nephrosis.

Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in puromycin aminonucleoside-induced nephrotic rats in order to establish the nature of the hypertriglyceridemia associated with this condition. Nephrotic rats had a plasma TG concentration 10-fold higher than the controls. In nephrotic rats TG secretion rate was elevated only 1.2-fold above the controls, suggesting that the catabolism of TG was also impaired. Lipolytic activities were determined in postheparin plasma (PHP) of the control and the nephrotic rats. There were no significant differences in either the activity of lipoprotein lipase (LPL) or hepatic lipase (HL). VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The half life (T12) was then determined by monitoring the clearance of plasma [3H]-VLDL-TG in normal recipient animals. The T12 of VLDL-TG from nephrotic rats was twice that of normal rats. The defect in VLDL-TG clearance could be partially rectified by preincubation with high-density lipoprotein (HDL) from normal rats, but not with HDL from nephrotic rats. VLDL from either nephrotic or normal rats were incubated with PHP of normal rats to assess the effectiveness of VLDL-TG as a substrate for PHP. The lipolytic rate for nephrotic VLDL was significantly lower than that for normal VLDL, suggesting that VLDL from nephrotic rats was somewhat resistant to the action of LPL and HL. When VLDL from nephrotic rats was preincubated with HDL from normal rats, the low lipolytic rate of VLDL-TG improved significantly. This was not observed when HDL from nephrotic rats was used for the preincubation. The results suggested that physical and/or chemical change of VLDL particles due to nephrosis results in a catabolic defect of VLDL-TG.