ABNORMALITIES IN HEPATIC LIPASE IN CHRONIC-RENAL-FAILURE - ROLE OF EXCESS PARATHYROID-HORMONE

Post-heparin hepatic lipase activity is reduced in chronic renal failu re (CRF), This could be due to reduced synthesis, decreased activity, and/or impaired secretion of the enzyme. Further, the factor(s) respon sible for such derangements are not elucidated. We examined hepatic li pase metabolism in normal, B-wk-old CRF rats, CRF-PTX (parathyroidecto mized) rats, and CRF and normal rats treated with verapamil (CRF-V, no rmal-V) using liver homogenate, hepatic cell culture for 8 h, and in v itro liver perfusion, The V-max, of hepatic lipase in liver homogenate was significantly (P < 0.01) reduced and the K-m was significantly (P < 0.01) increased in CRF rats, but the values were normal in CRF-PTX, CRF-V, and normal-V rats. Culture of hepatic cells for 8 h was associ ated with an increase in hepatic lipase activity but the increment in CRF rats was significantly (P < 0.01) lower than that of normal, CRF-P TX, CRF-V, and normal-V rats, Both parathyroid hormone (PTH)-(1-84) an d 1-34 inhibited the production of hepatic lipase in cultured cells fr om normal, CRF-PTX, CRF-V, and normal-V rats, The expression of the mR NA of the hepatic lipase was significantly reduced in CRF animals with the ratio between it and that of house keeping gene G3DPH being 15+/- 3% compared to 40+/-1.3% in normal, 44+/-2.9% CRF-PTX, 44+/-5.4% in CR F-V, and 39+/-3.9% in normal-V rats, Infusion of heparin to the in vit ro hepatic perfusion system increased the activity of hepatic lipase i n the effluent in all groups of rat except in CRF animals. Infusion of PTH-(1-34) in dose of 10(-6) M into the liver perfusion system inhibi ted the increase in post-heparin hepatic lipase activity, The data sho w that in CRF (a) the mRNA of hepatic lipase is downregulated, and hep atic lipase production, activity and release are impaired, (b) that th is is due to the state of secondary hyperparathyroidism of CRF since b oth acute and chronic excess of PTH were associated with these abnorma lities, (c) and that prevention of excess PTH by PTX of CRF rats or bl ocking the effect of PTH by treatment with verapamil corrected the der angement in hepatic lipase metabolism.