PLASMA TRIGLYCERIDE LEVELS ARE HIGHER IN NEPHROTIC THAN IN ANALBUMINEMIC RATS DESPITE A SIMILAR INCREASE IN HEPATIC TRIGLYCERIDE SECRETION

The relative contributions of increased hepatic secretion of triglycer ide (TG) and decreased TG catabolism to hypertriglyceridemia in the ne phrotic syndrome, and their relationship to urinary protein loss and r educed plasma colloid osmotic pressure (pi) remain unclear. We measure d the activity of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), two key enzymes of fatty acid synthesis in hepatic cytosol, in fed control rats, in rats with congenital analbuminemia (NA) that are free of proteinuria, and in rats with adriamycin-induced nephrotic sy ndrome (ADR). Both NA and ADR rats had decreased pi (respectively 13.2 +/- 0.3 and 10.7 +/- 0.4 mm Hg vs. control rats 18.3 +/- 0.7 mm Hg, P < 0.05), but only ADR rats had increased plasma TG (5.8 +/- 2.6 mmol/ liter vs. 1.5 +/- 0.2 mmol/liter in both control and NA rats, P < 0.05 ), and were proteinuric: 811 +/- 45 mg/day, P < 0.01 versus control an d NA rats. Total cytosolic ACC activity, expressed per g body weight, was increased in both NA and ADR rats by 45% and 39%, respectively (P < 0.05). Total FAS activity was increased by 65% and 115% in NA and AD R rats, respectively (P < 0.05). Thus low pi was consistently associat ed with an increase in total ACC and FAS activities in the livers of f ed rats. However, low pi was consistently associated with an increase in plasma TG only in ADR rats. Hepatic TG secretion rates, measured in vivo after blocking lipolysis with Triton WR-1339 in fasting animals, were increased by 33% in both ADR and NA rats as compared to controls (P < 0.05). Thus in the fasted state low pi was associated with an in crease in TG secretion rate. In fasted control rats plasma TG levels w ere low (0.5 +/- 0.05 mmol/liter). Plasma TG were increased in NA (2.1 +/- 2 mmol/liter; P < 0.05 vs, control), ADR (3.4 +/- 0.5 mmol/liter; P < 0.05 vs. control and NA) and in NA rats with ADR-induced proteinu ria (4.6 +/- 1.5 mmol/liter; P < 0.05 vs. control and NA). Since TG se cretion rates and involved liver enzyme activities are equally increas ed in both NA and ADR rats, whereas plasma TG concentration is consist ently higher in ADR than in NA rats, we suggest that the severe hypert riglyceridemia in nephrotic rats is due to a combination of hypoprotei nemia-linked increase in TG synthesis and a proteinuria-linked impairm ent of TG catabolism.