Hyperlipoproteinemia of aminonucleoside-induced nephrotic syndrome--modulation by glucocorticoids and triiodothyronine.
Triamcinolone or triiodothyronine (T3) was administered to rats with nephrosis induced by aminonucleoside of puromycin and to control nontreated rats. Triamcinolone produced hyperglycemia, hyperinsulinemia and liver glycogen deposition in control rats and to a lesser extent in nephrotic rats. Triamcinolone treatment did not affect plasma protein and albumin levels but increased the level of plasma triglycerides and cholesterol in the very low density lipoprotein (VLDL) and LDL but not high density lipoprotein fractions. The exacerbation of hyperlipoproteinemia was attributed both to increase hepatic lipid synthesis and delayed removal, since it was associated with the induction of hepatic acetyl-CoA carboxylase, the regulatory enzyme of lipogenesis, as well as with marked suppression of adipose tissue lipoprotein lipase (LPL). The hepatic lipase activity was found to be elevated in nephrotic rats but was suppressed by triamcinolone treatment, indicating a reduced capacity of VLDL to LDL conversion. T3 treatment resulted in serum glucose and insulin increases similar to triamcinolone, but more moderate in nephrotic vs. control rats, and in marked reduction in liver glycogen content. Plasma protein levels were not affected, but contrary to control rats, T3 treatment produced an elevation in serum triglycerides and cholesterol in nephrotic rats. The activity of several hepatic lipogenic enzymes, including acetyl-CoA carboxylase, was markedly elevated, as was the activity of gluconeogenic enzymes. Thus, the hyperlipoproteinemia on T3 treatment appeared to be mainly due to predomination of lipid synthesis over removal, since the activities of enzymes responsible for plasma lipid disposal, adipose tissue LPL and hepatic lipase were enhanced both in control and nephrotic rats. It is remarkable that both T3 and triamcinolone induce the lipogenic enzymes and apolipoproteins in the liver of nephrotic rats, already pronouncedly stimulated to replace the excreted plasma proteins. Thus, the nephrotic liver is able to respond to hormonal stimulation with further specific protein and lipid synthesis. It is also pertinent that the recovery from immunosuppressive treatment of human nephrosis, developing on an immune background, may result in more impressive amelioration of proteinuria and hypoproteinemia than of hyperlipoproteinemia because of the lipidemic effect of glucocorticoids.
Shafrir
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Department of Biochemistry, Hadassah University Hospital, Jerusalem, Israel.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005938:Glucocorticoids / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D006951:Hyperlipoproteinemias / Q000209:etiology / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D011692:Puromycin Aminonucleoside; D051381:Rats; D011919:Rats, Inbred Strains; D014221:Triamcinolone / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D001798:Blood Proteins; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D008074:Lipoproteins; D014284:Triiodothyronine; D014221:Triamcinolone; D011692:Puromycin Aminonucleoside; D008049:Lipase