HYPERLIPOPROTEINEMIA OF AMINONUCLEOSIDE-INDUCED NEPHROTIC SYNDROME - MODULATION BY GLUCOCORTICOIDS AND TRIIODOTHYRONINE

Triamcinolone or triiodothyronine (T-3) was administered to rats with nephrosis induced by aminonucleoside of puromycin and to control nontr eated rats. Triamcinolone produced hyperglycemia, hyperinsulinemia and liver glycogen deposition in control rats and to a lesser extent in n ephrotic rats. Triamcinolone treatment did not affect plasma protein a nd 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 hyperlipoprot einemia was attributed both to increased hepatic lipid synthesis and d elayed 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 rat s bur was suppressed by triamcinolone treatment, indicating a reduced capacity of VLDL Ca LDL conversion. T-3 treatment resulted in serum gl ucose and insulin increases similar to triamcinolone, but more moderat e in nephrotic vs. control rats, and in marked reduction in liver glyc ogen content. Plasma protein levels were not affected, but contrary to control rats, T-3 treatment produced an elevation in serum triglyceri des and cholesterol in nephrotic rats. The activity of several hepatic lipogenic enzymes, including acetyl-CoA carboxylase, was markedly ele vated, as was the activity of gluconeogenic enzymes. Thus, the hyperli poproteinemia on T-3 treatment appeared to be mainly due to predominat ion of lipid synthesis over removal, since the activities of enzymes r esponsible for plasma lipid disposal, adipose tissue LPL and hepatic l ipase were enhanced both in control and nephrotic rats. It is remarkab le that both T-3 and triamcinolone induce the lipogenic enzymes and ap olipoproteins in the liver of nephrotic rats, already pronouncedly sti mulated to replace the excreted plasma proteins. Thus, the nephrotic l iver is able to respond to hormonal stimulation with further specific protein and lipid synthesis. It is also pertinent that the recovery fr om immunosuppressive treatment of human nephrosis, developing on an im mune background, may result in more impressive amelioration of protein uria and hypoproteinemia than of hyperlipoproteinemia because of the l ipidemic effect of glucocorticoids.