Hepatic triglyceride lipase promotes low density lipoprotein receptor-mediated catabolism of very low density lipoproteins in vitro

We demonstrate here that hepatic triglyceride lipase (HTGL) enhances VLDL d egradation in cultured cells by a LDL receptor-mediated mechanism, VLDL bin ding at 4 degrees C and degradation at 37 degrees C by normal fibroblasts w as stimulated by HTGL in a dose-dependent manner. A maximum increase of up to 7-fold was seen at 10 mu g/ml HTGL, Both VLDL binding and degradation we re significantly increased (4-fold) when LDL receptors were up-regulated by treatment with lovastatin, HTGL also stimulated VLDL degradation by LDL re ceptor-deficient FH fibroblasts but the level of maximal degradation was 40 -fold lower than in lovastatin-treated normal fibroblasts, A prominent role for LDL receptors was confirmed by demonstration of similar HTGL-promoted VLDL degradation by normal and LRP-deficient murine embryonic fibroblasts, HTGL enhanced binding and internalization of apoprotein-free triglyceride e mulsions, however, this was LDL receptor-independent. HTGL-stimulated bindi ng and internalization of apoprotein-free emulsions was totally abolished b y heparinase indicating that it was mediated by HSPG, In a cell-free assay HTGL competitively inhibited the binding of VLDL to immobilized LDL recepto rs at 4 degrees C suggesting that it may directly bind to LDL receptors but may not bind VLDL particles at the same time. We conclude that the ability of HTGL to enhance VLDL degradation is due to its ability to concentrate l ipoprotein particles on HSPG sites on the cell surface leading to LDL recep tor-mediated endocytosis and degradation.