Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion

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 triglyceride (TG) and decreased TG catabolism to hypertriglyceridemia in the nephrotic syndrome, and their relationship to urinary protein loss and reduced plasma colloid osmotic pressure (π) remain unclear. We measured 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 syndrome (ADR). Both NA and ADR rats had decreased π (respectively 13.2 ± 0.3 and 10.7 ± 0.4mm Hg vs. control rats 18.3 ± 0.7mm 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 and 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 ADR rats, respectively (P < 0.05). Thus low π was consistently associated with an increase in total ACC and FAS activities in the livers of fed rats. However, low π 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 π was associated with an increase in TG secretion rate. In fasted control rats plasma TG levels were 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 proteinuria (4.6 ±1.5 mmol/liter; P < 0.05 vs. control and NA). Since TG secretion rates and involved liver enzyme activities are equally increased in both NA and ADR rats, whereas plasma TG concentration is consistently higher in ADR than in NA rats, we suggest that the severe hypertriglyceridemia in nephrotic rats is due to a combination of hypoproteinemia-linked increase in TG synthesis and a proteinuria-linked impairment of TG catabolism