The Studies on the Mechanism of Hypertriglyceridemia:With Special References to the Production of Triglyceride

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The concentration of plasma triglyceride (TG) will tend to rise or fall as its flux in or out of plasma is varied. Therefore, to determine if a rise in plasma TG concentration is caused primarily by increased secretion or by decreased removal, it is necessary to measure the removal rate and TG secretion rate. Clinical Study First, we demonstrated the relationship between plasma TG concentration and the fractional removal rate of exogenous TG by using the intravenous fat tolerance tests. Secondly, we reported here the new method for measuring TG secretion rates in humans. Intravenous fat tolerance tests according to the Carlson's method were performed in 3 control subjects and 10 hypertriglyceridemic patients. The fractional removal rates (K2 value) of Intralipid negatively correlated with fasting plasma TG concentraion. Furthermore, after the injection of heparin, the clearance of Intralipid was enhanced and K2 value increased. It is likely that we can use these fractional removal rates as a index of the removal rates of endogenous TG. These results suggest that intravenous fat tolerance test is suitable for assessing the removal rate and this method is possible to serve as a clinical routine test. We demonstrated the new method for measuring TG secretion rates in control subjects and hyertriglyceridemic patients by using protamine sulfate which is known to inhibit TG removal from plasma. Since the administration of protamine sulfate may not completely inhibit the clearance of VLDL-TG, the fractional removal rates of Intralipid before and after the treatment with protamine sulfate were calculated by intravenous fat tolerance tests. The elimination of exogenous TG from blood was delayed till 30 minutes after the administration of protamine sulfate. The inhibition of TG clearance was not complete and the inhibition rates showed the variability on individual subjects. Their rates varied from 34% to 83%. Then, estimating the TG secretion rates by using protamine sulfate, we should consider the inhibition rates of clearance by protamine sulfate and correct those values. Then, on another day, heparin (20u/kg) was injected followed 5 minutes later by protamine sulfate (1mg/kg). Thereafter blood samples were taken every 10 minutes over a period by one hour. VLDL was separated by ultracentrifugation and both LDL and HDL were separated by the precipitation's method. TG concentration were estimated with Fletcher's method. Both whole plasma TG and VLDL-TG concentration increased almost linearily till 30 minutes after the administration of protamine sulfate. The increments in whole plasma TG and in VLDL-TG for the hypertriglyceridemic patients were more pronounced than those of control subjects. The increments in whole plasma TG and VLDL-TG actually obained from experiments correlated with fasting TG concentration. However, considering the inhibition rates of clearance by protamine sulfate, only the corrected increments in VLDL-TG showed the correlation with fasting plasma TG concentration. TG secretion rates were calculated from those increments in whole plasma TG and VLDL-TG with and without considering the inhibition rates by protamine sulfate. There was positive correlation between fasting plasma TG and these TG secretion rates except one obtained from the corrected increments in whole plasma TG. These studies suggest that the administration of protamine sulfate may provide a valuable tool for estimating TG secretion rates. However, TG secretion rates obtained from our experiments are higher than those which have been previously calculated by the isotopical technique. The explanation for these results might be that TG secretion rates were enhanced under heparin injection. It is concluded that the cause of hypertriglyceridemia is due to metabolic alterations both in splanchnic production and clearance from the blood. Animal Experiment
Japan Society of Clinical Chemistryの論文

The Studies on the Mechanism of Hypertriglyceridemia:With Special References to the Production of Triglyceride

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