scholarly journals Origin of hepatic very-low-density lipoprotein triacylglycerol: the contribution of cellular phospholipid

1996 ◽  
Vol 320 (2) ◽  
pp. 673-679 ◽  
Author(s):  
David WIGGINS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cell Protein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Exogenous Fatty Acid ◽  
Cellular Phospholipid

When rat hepatocytes were cultured for 24 h in the absence of exogenous fatty acid, the amount of very-low-density lipoprotein (VLDL) triacylglycerol (TAG) secreted (114±14 µg/mg of cell protein) could not be accounted for by the mass of TAG lost from the cells (29±6.1 µg/mg of cell protein) during this period (n = 12). Of the balance (85±14 µg/mg; 94±15 nmol/mg), a maximum of only 37 nmol/mg of cell protein of TAG could be accounted for by fatty acids synthesized de novo. When labelled exogenous oleate (initial concentration, 0.75 mM) was present in the culture medium, the net gain in cellular plus VLDL TAG (253±38 µg/mg of cell protein per 24 h) was greater than that contributed by the exogenous fatty acid (155±18.2 µg/mg of cell protein, n = 5). Again, the balance (98.8±18.2 µg/mg of cell protein per 24 h) was too great to be accounted for by fatty acid synthesis de novo. In experiments in which cellular glycerolipids were prelabelled with [9,10(n)-3H]oleic acid, following removal of the labelled fatty acid, there was a net increase in labelled cellular plus VLDL TAG over the next 24 h. That cellular phospholipids are the source of a substantial part of the excess TAG synthesized is supported by the following evidence. (1) The loss of prelabelled cellular phospholipid during culture was greater than could be accounted for by secretion into the medium. (2) During culture of cells prelabelled with 1,2-di-[1-14C]palmitoyl phosphatidylcholine, a substantial amount of label was secreted as VLDL TAG. (3) In pulse–chase experiments, the kinetics of labelled phospholipid turnover were consistent with conversion into a non-phospholipid pool. The enzymology involved in the transfer of phospholipid fatty acids into TAG is probably complex, but the present results suggest that this pathway may represent an important route by which extracellular fatty acids are channelled into VLDL TAG.

scholarly journals Extracellular fatty acids are not utilized directly for the synthesis of very-low-density lipoprotein in primary cultures of rat hepatocytes

1992 ◽  
Vol 287 (3) ◽  
pp. 749-753 ◽  
Author(s):  
G F Gibbons ◽  
S M Bartlett ◽  
C E Sparks ◽  
J D Sparks
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Acid Concentration ◽  
Low Density Lipoprotein ◽  
Primary Cultures ◽  
Density Lipoprotein ◽  
Fatty Acid Concentration ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Extracellular Fatty Acid

In hepatocytes cultured in the presence of oleate (initial concn. 0.75 mM), the secretion of very-low-density lipoprotein (VLDL) triacylglycerol and, to a lesser extent, apoprotein B (apoB) increased with time, whereas there was a large decline in the extracellular concentration of fatty acid. There was thus no synchronous relationship between the extracellular fatty acid concentration and the secretion of VLDL. Rather, the appearance of VLDL in the medium was dependent on the intracellular triacylglycerol concentration. At a given concentration of extracellular fatty acid, cells depleted of triacylglycerol secreted less VLDL triacylglycerol and apoB than did control cells. A similar pattern was observed for triacylglycerol newly synthesized from extracellular [3H]oleate. By contrast, the synthesis and output of ketone bodies were directly dependent on the fatty acid concentration of the medium. These results suggest that, at least for oleic acid, extracellular fatty acids are not utilized directly for VLDL assembly, but first enter a temporary intracellular storage pool of triacylglycerol, which is the immediate precursor of secreted triacylglycerol. The size of this pool then determines the rate of secretion of VLDL triacylglycerol apoB. Ketogenesis, on the other hand, relies mainly on the direct utilization of extracellular fatty acids.

scholarly journals Contribution of very low-density lipoprotein triglyceride fatty acids to postabsorptive free fatty acid flux in obese humans

Metabolism ◽  
2014 ◽  
Vol 63 (1) ◽  
pp. 137-140 ◽  
Author(s):  
Nikki C. Bush ◽  
Jessica M. Triay ◽  
Nicola W. Gathaiya ◽  
Kazanna C. Hames ◽  
Michael D. Jensen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density

scholarly journals Insulin and non-esterified fatty acids. Acute regulators of lipogenesis in perfused rat liver

1982 ◽  
Vol 204 (2) ◽  
pp. 433-439 ◽  
Author(s):  
D L Topping ◽  
P A Mayes
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Biosynthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Esterified Fatty Acids ◽  
Equilibrium Concentrations ◽  
Glucose Output

Livers from fed rats were perfused with whole rat blood and infused with oleate to maintain constant concentrations of serum non-esterified fatty acids over a wide physiological range. Infusion of insulin opposed the antilipogenic effects of increasing concentrations of serum non-esterified fatty acids. Secretion of very-low-density-lipoprotein triacylglycerols was directly proportional to the concentration of serum non-esterified fatty acids and was increased by insulin. The secretion of newly-synthesized fatty acids in very-low-density-lipoprotein triacylglycerols decreased with increasing concentrations of serum non-esterified fatty acid. Insulin opposed this change. Cholesterol biosynthesis was unaffected by alterations in concentration of serum non-esterified fatty acid but was increased by insulin. Equilibrium concentrations of perfusate lactate and glucose were increased by serum non-esterified fatty acids but steady-state rates of hepatic glucose output and lactate uptake were unchanged. Insulin decreased perfusate glucose concentrations and abolished the increase in its concentration that resulted from increases in non-esterified fatty acid concentrations.

scholarly journals The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas

1992 ◽  
Vol 284 (2) ◽  
pp. 457-462 ◽  
Author(s):  
D Wiggins ◽  
G F Gibbons
Keyword(s):  
Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Intracellular Pool ◽  
Hepatocyte Cultures ◽  
Vldl Secretion ◽  
Vldl Assembly ◽  
Hepatic Triacylglycerol

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.

scholarly journals The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo

1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson
Keyword(s):  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apoprotein B ◽  
Preferential Uptake ◽  
Triacylglycerol Fraction

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

scholarly journals Chronic exogenous hyperinsulinaemia does not modify the acute inhibitory effect of insulin on the secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B in primary cultures of rat hepatocytes

1996 ◽  
Vol 314 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Catherine S. BOURGEOIS ◽  
David WIGGINS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Primary Cultures ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Cell Protein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Plasma Insulin Concentration

Male Wistar rats were fitted with subcutaneous osmotic minipumps that delivered insulin at a constant rate of 0.20 i.u./h for 7 days. This treatment raised the plasma insulin concentration from 31±4 to 201±64 μ-i.u./ml. Hepatocytes prepared from the hyperinsulinaemic animals secreted very-low-density lipoprotein (VLDL) triacylglycerol (TAG) at a higher rate (172±21 μg per 24 h per mg cell protein) than did those from sham-operated controls (109±12 μg per 24 h per mg) (P < 0.05). However, chronic exogenous hyperinsulinaemia had no stimulatory effect on the secretion of VLDL apolipoprotein B (apoB) in derived hepatocytes compared with those from the sham-operated controls (2.32±0.38 compared with 3.09±0.40 μg per 24 h per mg). Hepatocytes from the hyperinsulinaemic rats thus secreted larger VLDL particles as evidenced by the increased TAG:apoB ratio (78.4±13.1 compared with 38.4±7.6; P < 0.05). In hepatocytes from the hyperinsulinaemic rats a larger proportion of the newly synthesized TAG was secreted as VLDL. Hepatocytes from the hyperinsulinaemic and the sham-operated control animals were equally sensitive to the inhibitory effect of insulin added in vitro on the secretion of VLDL TAG. Insulin added in vitro to the culture medium of hepatocytes from hyperinsulinaemic animals significantly decreased the TAG:apoB ratio of the secreted VLDL. This change did not occur in hepatocytes from sham-operated rats. These results suggest that, in vivo, chronic hyperinsulinaemia is not in itself sufficient to desensitize the liver to the acute inhibitory effect of insulin on the secretion of VLDL.

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