Irradiation-induced free cholesterol accumulation in very-low-density lipoproteins. Role of lipoprotein lipase deficiency.

Irradiation of rabbits induced an accumulation of free cholesterol in VLDL fraction. In the present study, an attempt was made to explain the abnormal free cholesterol enhancement. The study demonstrated that lecithin:cholesterol acyltransferase activity was normal in irradiated rabbits. In addition, electron microscopy examination of HDL revealed no changes after irradiation: spherical particles were present. On the other hand, ACAT activity was increased while neutral and acidic cholesteryl esterases were strongly decreased. Moreover, HMG-CoA reductase was 3-fold reduced after irradiation. These results show that neither cholesterol esterification nor cholesterol ester hydrolysis nor cholesterol biosynthesis are responsible for this increase of free cholesterol in VLDL. In contrast, we have shown that extra-hepatic lipoprotein lipase was deficient in irradiated rabbit plasma although synthesis in the adipocytes is normal. To investigate a hypothetical deficiency of VLDL catabolism, we performed experiments with injection of heparin and with labeled VLDL. These experiments show that, in irradiated rabbits, VLDL were not catabolized, since the radioactivity was recovered only in the VLDL fraction. This impaired VLDL removal was compatible with the deficiency of extra-hepatic lipoprotein lipase activity.