ヒト肝性トリグリセリドリパーゼ(HTGL)の生理作用の解明

Abstract

The purpose of this study is to evaluate changes in hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL) as a cause of dyslipoproteinemia in hypothyroidism. Hypothyroidism is associated with pronounced hypercholesterolemia and moderate hypertriglyceridemia. Recent studies suggest that such changes in serum lipids result from the decrease in LDL-receptors and also HTGL and/or LPL activities. In order to accurately evaluate the correlation between both lipases and lipoprotein abnormalities in patients with hypothyroidism, we measured LPL and HTGL mass concentrations in postheparin plasma by means of a sandwich-enzyme immunoassay (EIA) using two distinct monoclonal antibodies before and after treatment with thyroid hormone.Seven patients with untreated hypothyroidism and euthyroid normal controls (n=76) were studied. Hypothyroidism group (H) consisted of 3 males and 4 females (age 60±5 years) and the control group (N) of 46 males and 30 females (age 42±13 years). The plasma cholesterol (C) and triglyceride (TG) levels were significantly increased in the H group compared to the N group: 327±27 vs. 192±27ma/dl and 145±24 vs 88±33mg/dl, respectively. There was no difference in HDL-C (61.2±5.7 vs. 63.1±6.6mg/dl). HTGL was markedly reduced (79%) in the H group (264±57 vs. 1, 252±55ng/ml), while LPL was only slightly reduced (16%) (153±17 vs. 182±5ng/ml). The H group showed a hyperlipidemia of IIa (n=5) or IIb (n=2) as a WHO phenotype. After the patients were treated with thyroid hormone, HTGL level was drastically increased from 264±57ng/ml to 858±115ng/ml, and the LPL level also increased from 153±17ng/ml to 201±29ng/ml. Plasma C level decreased from 327±27 to 234±3mg/dl, and TG from 145±24 to 78±13mg/dl. By plotting all the patient data before and after the treatment, HTGL showed a positive correlation with FT3 (r=0.86) and negative correlation with TSH (r=-0.66). HTGL showed significant inverse correlations with LDL-TG/apoB (r=-0.74) and HDL-TG/apoA (r=-0.74). Our data indicates that HTGL mass concentration is regulated by thyroid hormone level leading us to conclude that HTGL is closely related to the metabolism of triglyceride-rich LDL and HDL particles.