scholarly journals The intracellular triacylglycerol/fatty acid cycle: a comparison of its activity in hepatocytes which secrete exclusively apolipoprotein (apo) B100 very-low-density lipoprotein (VLDL) and in those which secrete predominantly apoB48 VLDL

1998 ◽  
Vol 332 (3) ◽  
pp. 667-672 ◽  
Author(s):  
Andrew M. SALTER ◽  
David WIGGINS ◽  
Victoria A. SESSIONS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Human Hepatocytes ◽  
Cell Protein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Acid Cycle ◽  
Vldl Secretion ◽  
Vldl Assembly

Hamster hepatocytes, like human hepatocytes, secrete triacylglycerol (TAG) as very-low-density lipoprotein (VLDL) in association with apolipoprotein (apo) B100, whereas in the rat, TAG is secreted predominantly in association with apoB48. Nevertheless, in hepatocytes from both species, a minimum of between 60% and 70% [69.1±1.4% (hamster), 60.6±2.5% (rat)] of the VLDL TAG was secreted following lipolysis and re-esterification of intracellular TAG. The fractional rates of hepatocellular TAG turnover (lipolysis and re-esterification) were similar in both species [1.83±0.28 pools/24 h (hamster), 1.39±0.23 pools/24 h (rat)]. Comparison of the relative changes in the 3H and 14C specific radioactivities of the VLDL and cellular TAG, pre-labelled with [3H]glycerol and [4C]oleate, suggested that fatty acids released by lipolysis either were recruited directly into a VLDL assembly pool or were recycled to the cellular pool following re-esterification. Recycling in the hamster was somewhat greater than in the rat (66.1±5.7% versus 53.7±4.8% of TAG lipolysed respectively). Similarly, a larger proportion of newly synthesized TAG was retained within the cell, rather than secreted as VLDL, in the hamster compared with the rat (37.9±2.8% versus 20±3.8%, P< 0.01). These factors may have contributed to the somewhat lower rate of VLDL TAG secretion in the hamster hepatocytes compared with those from the rat (43.3±4.2 versus 96.4±3.4 µg/24 h per mg of cell protein). Rat hepatocytes were more sensitive to inhibition of VLDL secretion by insulin than were those from hamster. In neither case did insulin affect total or fractional TAG turnover. The results suggest that assembly of both apoB100 VLDL and apoB48 VLDL is associated with efficient intracellular TAG lipolysis.

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 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.

Acetoacetic acid induces oxidative stress to inhibit the assembly of very low density lipoprotein in bovine hepatocytes

2016 ◽  
Vol 83 (4) ◽  
pp. 442-446 ◽  
Author(s):  
Xiaoxia Shi ◽  
Dangdang Li ◽  
Qinghua Deng ◽  
Zhicheng Peng ◽  
Chenxu Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Acetoacetic Acid ◽  
Density Lipoprotein Receptor ◽  
Potential Link ◽  
Vldl Assembly

Dairy cows with fatty liver or ketosis exhibit hyperketonemia, oxidative stress, and a low rate of very low density lipoprotein (VLDL) assembly, and there may be a potential link among these characteristics. Therefore, the objective of this study was to determine the effect of acetoacetic acid (AcAc) on the assembly of VLDL in cow hepatocytes. Cultured cow hepatocytes were treated with different concentrations of AcAc with or without N-acetylcysteine (NAC, an antioxidant). AcAc treatment decreased the mRNA expression and activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and significantly increased malondialdehyde (MDA) content, indicative of oxidative stress. Furthermore, AcAc treatment significantly down-regulated the mRNA expression of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE), and low density lipoprotein receptor (LDLR), which thus decreased VLDL assembly and increased triglyceride (TG) accumulation in these bovine hepatocytes. Importantly, NAC relieved AcAc-induced oxidative stress and increased VLDL assembly. In summary, these results suggest that AcAc-induced oxidative stress affects the assembly of VLDL, which increases TG accumulation in bovine hepatocytes.

scholarly journals Shedding of syndecan-1 from human hepatocytes alters very low density lipoprotein clearance

Hepatology ◽  
2011 ◽  
Vol 55 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Yiping Deng ◽  
Erin M. Foley ◽  
Jon C. Gonzales ◽  
Philip L. Gordts ◽  
Yulin Li ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Hepatocytes ◽  
Very Low Density Lipoprotein ◽  
Low Density

scholarly journals Long-term maintenance of high rates of very-low-density-lipoprotein secretion in hepatocyte cultures. A model for studying the direct effects of insulin and insulin deficiency in vitro

1989 ◽  
Vol 263 (3) ◽  
pp. 937-943 ◽  
Author(s):  
J M Duerden ◽  
S M Bartlett ◽  
G F Gibbons
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Secretory Process ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Triacylglycerol Synthesis ◽  
Vldl Secretion ◽  
Pre Treatment

High rates of hepatic cellular triacylglycerol synthesis and very-low-density-lipoprotein (VLDL) triacylglycerol output were maintained in vitro for at least 3 days when hepatocytes were cultured in a medium lacking insulin but supplemented with 1 microM-dexamethasone, 10 mM-lactate, 1 mM-pyruvate and 0.75 mM-oleate (supplemented medium). Under these conditions VLDL output remained constant, whereas cell triacyglycerol content increased 10-fold over 3 days, suggesting that the secretory process was saturated. Insulin, present during the first 24 h period, enhanced the storage of cellular triacylglycerol by inhibiting the secretion of VLDL. This stored triacyglycerol was subsequently released into the medium as VLDL if insulin was removed. With the supplemented medium the increased rate of VLDL secretion after insulin removal exceeded that observed under ‘saturating’ conditions, suggesting that pre-treatment with insulin enhanced the capacity for VLDL secretion. In contrast with the short-term (24 h) effects of insulin, longer-term exposure (greater than 48 h) to insulin enhanced the secretion of VLDL compared with insulin-untreated cultures. Under these conditions, insulin increased the net rates of triacylglycerol synthesis. The results suggest that insulin affects the secretion of VLDL triacylglycerol by two distinct and opposing mechanisms: first, by direct inhibition of secretion; second by increasing triacylglycerol synthesis, which stimulates secretion. The net effect at any time depends upon the relative importance of each of these processes.

Apolipoprotein (apo) E modulates hepatic very low density lipoprotein (VLDL) assembly and secretion

2000 ◽  
Vol 151 (1) ◽  
pp. 158 ◽  
Author(s):  
Y. Huang ◽  
W.J. Brecht ◽  
X.Q. Liu ◽  
Y. Wang ◽  
J.M. Taylor ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apo E ◽  
Vldl Assembly
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