Cytoplasmic triacylglycerols and cholesteryl esters are degraded in two separate catabolic pools in cultured human fibroblasts.
The sources and the catabolic pathways of cytoplasmic pools of triacylglycerols and cholesteryl esters have been comparatively investigated in cultured fibroblasts from normal subjects and from patients affected with neutral lipid storage disease (NLSD) and Wolman disease (WD). (i) Endogenously biosynthesized triacylglycerols and cholesteryl esters were degraded extra-lysosomally since they were catabolized at similar rates in normal and in WD fibroblasts. In NLSD fibroblasts, the degradation of endogenous triacylglycerols was severely deficient, whereas that of endogenous cholesteryl esters was in the normal range. (ii) Reconstituted high density lipoproteins (HDL) containing radiolabelled [3H]triolein and cholesteryl [14C]oleate were taken up by cultured fibroblasts and rapidly degraded in a non-lysosomal compartment. In NLSD fibroblasts the degradation of HDL-[3H]triolein was blocked whereas that of HDL-[14C]cholesteryl oleate was in the normal range. These data suggest that: (i) the cytoplasmic pools of triacylglycerols and cholesteryl esters originate from HDL uptake and from endogenous biosynthesis as well; (ii) cytoplasmic (non-lysosomal) triacylglycerols and cholesteryl esters are degraded by two separate catabolic pathways.
Hilaire
N
N
Department of Biochemistry, Faculty of Medicine in Rangueil, University Paul Sabatier, Toulouse, France.
Nègre-Salvayre
A
A
Salvayre
R
R
D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000096:biosynthesis / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*; D014304:Triolein / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D014280:Triglycerides; D014316:Tritium; D014304:Triolein