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 (pi) 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 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 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 pi was consistently associated with an increase in total ACC and FAS activities in the livers of fed 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Joles
J A
JA
Department of Neprology and Hypertension, Faculty of Medicine, Utrecht University, The Netherlands.
Bijleveld
C
C
van Tol
A
A
Geelen
M J
MJ
Koomans
H A
HA
D000818:Animals; D004317:Doxorubicin; D004798:Enzymes / Q000378:metabolism; D005215:Fasting; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009401:Nephrosis / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000172:deficiency*; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism*
D004798:Enzymes; D008074:Lipoproteins; D012709:Serum Albumin; D014280:Triglycerides; D004317:Doxorubicin