Acquired VLDL receptor deficiency in experimental nephrosis.
Nephrotic syndrome (NS) is commonly associated with elevation of plasma very low density lipoprotein (VLDL) and triglyceride concentrations. VLDL receptor (VLDL-R) is a novel protein that specifically binds and internalizes VLDL particles and is primarily distributed in heart, skeletal muscle, brain and adipose tissue. Based on these properties, VLDL-R is thought to play a role in VLDL and triglyceride metabolism. The present study was undertaken to test the hypothesis that elevation of plasma VLDL in NS may be, in part, related to VLDL-R deficiency. To this end, heart and skeletal muscle VLDL-R protein (Western blot) and mRNA (Northern blot) were measured at various points in the course of puromycin-induced NS in rats. The results were compared with those obtained in the placebo-treated normal control animals. The NS group showed a significant decline in VLDL-R protein (relative to total plasma membrane protein mass) in the heart and skeletal muscle paralleling the rise in plasma VLDL and triglyceride concentrations. The fall in VLDL-R protein was accompanied by a parallel decline in VLDL-R mRNA in the heart but not skeletal muscle. VLDL-R protein was directly related to proteinuria and inversely related to plasma VLDL and triglyceride concentrations. In conclusion, puromycin-induced NS in rats is associated with profound reduction in heart and skeletal muscle VLDL receptor protein. Acquired VLDL-R deficiency, shown for the first time here, may contribute to elevation of plasma concentration of triglyceride-rich VLDL in the nephrotic rat. Recognition of this abnormality reveals another dimension of the complex dysregulation of lipid metabolism in NS. The precise mechanism responsible for NS-induced VLDL-R deficiency in this model is not clear and awaits further investigation.
Liang
K
K
Department of Medicine, University of California, Irvine, USA.
Vaziri
N D
ND
D000818:Animals; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism*; D011691:Puromycin; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D011691:Puromycin