Gene expression of lipoprotein lipase in experimental nephrosis.
Nephrotic syndrome (NS) is commonly associated with marked hypertriglyceridemia, impaired triglyceride-laden lipoprotein clearance, and reduced peripheral tissue uptake of triglycerides from chylomicrons. Lipoprotein lipase (LPL) is the rate-limiting step in triglyceride-rich lipoprotein metabolism. Earlier studies have demonstrated a marked reduction of plasma post-heparin lipolytic activity and LPL protein in NS. However, the effect of NS on gene expression of LPL has not been elucidated. We studied rats with puromycin aminonucleoside-induced NS and the placebo-injected control animals. Heart, soleus muscle, and fat body LPL activity, protein mass, and mRNA were measured and plasma lipid levels were quantitated. The NS group exhibited marked proteinuria, hypoalbuminemia, and hypertriglyceridemia. This was associated with significant reductions of LPL activity and immunodetectable protein in the heart, adipose tissue, and soleus muscle in the NS group. The reduction in LPL protein mass in the tissues tested was accompanied by a parallel reduction in LPL mRNA of the heart but not of either adipose tissue or skeletal muscle, suggesting translational or posttranslational modifications. A negative correlation was found between plasma triglyceride concentration and the LPL, activities of the tissues tested in the study population. Thus this study has revealed a significant down-regulation of tissue LPL protein in experimental NS. This phenomenon can, in part, account for hypertriglyceridemia, impaired catabolism of chylomicrons, and very low-density lipoprotein by peripheral tissues and decreased postheparin lipolytic activity in NS.
Liang
K
K
Department of Medicine, University of California, Irvine, USA.
Vaziri
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ND
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015228:Hypertriglyceridemia / Q000209:etiology; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009404:Nephrotic Syndrome / Q000201:enzymology*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D008074:Lipoproteins; D012333:RNA, Messenger; D014280:Triglycerides; D011692:Puromycin Aminonucleoside; D008071:Lipoprotein Lipase