The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas.
In hepatocyte cultures maintained in the absence of extracellular fatty acids, at least 70% of the secreted very-low-density lipoprotein (VLDL) triacylglycerol was derived via lipolysis of intracellular triacylglycerol. This proportion was unchanged when the cells were exposed for 24 h to insulin or glucagon, hormones which decreased the overall secretion of intracellular triacylglycerol, or to chloroquine or tolbutamide, agents which inhibit lysosomal lipolysis. The rate of intracellular lipolysis was 2-3-fold greater than that required to maintain the observed rate of triacylglycerol secretion. Most of the fatty acids released were returned to the intracellular pool. Neither insulin nor glucagon had any significant effect on the overall lipolysis and re-esterification of intracellular triacylglycerol. In these cases a greater proportion of the released fatty acids re-entered the cellular pool, rather than being recruited for VLDL assembly. Tolbutamide inhibited intracellular lipolysis, but suppressed VLDL secretion to a greater extent. 3,5-Dimethylpyrazole did not affect lipolysis or VLDL secretion. The increased secretion of VLDL triacylglycerol observed after exposure of cells to insulin for 3 days was not accompanied by an increased rate of intracellular lipolysis. However, a larger proportion of the triacylglycerol secreted under these conditions may not have undergone prior lipolysis.
Wiggins
D
D
Metabolic Research Laboratory, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, U.K.
Gibbons
G F
GF
D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008066:Lipolysis / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D010187:Pancreatic Hormones; D013453:Sulfonylurea Compounds; D014280:Triglycerides