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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. INTRODUCTIONTreatment of hepatocytes in culture with insulin for periods less than 24 h results in a decreased net rate of mobilization of cytosolic triacylglycerol [1] and a decrease in the rate of very-lowdensity lipoprotein (VLDL) lipid [1][2][3][4][5] and apoprotein B (apoB) secretion [6][7][8][9][10]. It has previously been suggested that at least some of the VLDL triacylglycerol is derived from the cytosolic storage pool via lipolysis, followed by re-esterification in the endoplasmic reticulum [11][12][13][14]. There has been no attempt to quantify this in mammalian liver. Glucagon and cyclic AMP

1. Substrate movements in forearm muscle and subcutaneous adipose tissue were studied, by measurement of arteriovenous differences and blood flow, in seven normal subjects after an overnight fast and then for 6 h after ingestion of a mixed meal. Overall substrate balances were examined in terms of the flux of gram-atoms of carbon. 2. As found previously, the forearm was approximately in carbon balance (import equal to export) after the overnight fast, whereas adipose tissue was a net exporter of carbon, mainly in the form of non-esterified fatty acids. 3. After the meal, arterialized plasma concentrations of glucose and lactate rose sharply (peak at 60 min), whereas those of non-esterified fatty acids and glycerol fell (nadir at 60-120 min). Plasma triacylglycerol concentrations rose slowly to peak at 240 min;much of this rise was accounted for by a rise in the chylomicron fraction. 4. Both tissues took up glucose at an increased rate after the meal. Release of non-esterified fatty acids and glycerol from adipose tissue was suppressed. Clearance of triacylglycerol by both tissues increased after the meal, but was more marked in adipose tissue, where the fractional extraction of chylomicron-triacylglycerol reached 44% at 240 min. 5. The forearm rapidly became a considerable net importer of carbon, and remained so until 6 h after the meal when it was again in approximate carbon balance. Glucose uptake dominated the forearm carbon balance. Adipose tissue was a net importer of carbon from 30 min until 5 h after the meal and then reverted to net export. Clearance of triacylglycerol carbon made the largest contribution to this positive balance, but towards the end of the study this was increasingly counterbalanced by simultaneous non-esterified fatty acid release.

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