scholarly journals Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

1978 ◽  
Vol 77 (3) ◽  
pp. 735-742 ◽  
Author(s):  
EP Reaven ◽  
GM Reaven
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Isolated Hepatocytes ◽  
Experimental Diet ◽  
Vldl Secretion ◽  
Morphometric Methods ◽  
Rat Livers ◽  
Vldl Triglyceride ◽  
Lard Diet ◽  
Tubulin Content

The fact that colchicines inhibits hepatic secretion of very low density lipoprotein (VLDL) particles has been interpreted to mean that microtubules are involved in hepatic VLDL secretion. To further define this relationship, we have attempted to see if changes in hepatic VLDL secretion are associated with changes in hepatocyte microtubule or tubulin content. Accordingly, hepatic secretion of VLDL was increased in rats, and the hepatocyte content of both microtubules (using quantitative morphometric methods) and tubulin (using a time-decay colchicine binding assay) was determined. In acute experiments, VLDL secretion was increased by perfusion of isolated rat livers for 2 h with varying concentrations of free fatty acids (FFA). Results indicate that hepatic VLDL triglyceride (TG) secretion at perfusate FFA levels of 0.7 μEq/ml is threefold greater (P < 0.01) than when livers are perfused without added FFA. However, no differences are observed in the content of microtubules in these livers: specifically, microtubules occupy 0.029 percent of hepatocyte cytoplasm in livers perfused without FFA and 0.030 percent of cytoplasm in livers perfused with FFA. In chronic experiments, rats were fed for 1 wk with either standard rat chow or a hyperlipidemic (sucrose/lard) diet. With the experimental diet, plasma triglyceride levels increase threefold over controls, and liver VLDL-TG production, as determined by [(3)H]glycerol turnover studies, is 55 percent greater (P < 0.01) than controls. However, microtubules occupy 0.027 percent of the cytoplasm of hepatocyte cytoplasm whether rats are on standard or hyperlipidemic diets. Furthermore, the tubulin content of isolated hepatocytes does change, and represents 1 percent of hepatocyte soluble protein, irrespective of diet. These results suggest that increases in hepatic VLDL secretion can occur without any demonstrable change in hepatocyte assembled microtubule or tubulin content, and raise questions as to the role played by microtubules in hepatic VLDL secretion.

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.

Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia

2020 ◽  
Vol 105 (10) ◽  
pp. 3152-3164
Author(s):  
Véronique Ferchaud-Roucher ◽  
Yassine Zair ◽  
Audrey Aguesse ◽  
Michel Krempf ◽  
Khadija Ouguerram
Keyword(s):  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Omega 3 ◽  
Pufa Supplementation ◽  
Multicompartmental Model ◽  
Neutral And Polar Lipids ◽  
Before And After ◽  
Positive Correlations ◽  
Vldl Triglyceride

Abstract Context Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. Objectives In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Methods Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Results Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Conclusion Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids

Intestinal triglycerides are derived from both endogenous and exogenous sources

1985 ◽  
Vol 248 (2) ◽  
pp. G164-G169 ◽  
Author(s):  
Y. F. Shiau ◽  
D. A. Popper ◽  
M. Reed ◽  
C. Umstetter ◽  
D. Capuzzi ◽  
...  
Keyword(s):  
Small Intestine ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Dietary Lipid ◽  
Acid Load ◽  
Endogenous Substrates ◽  
Quantitative Contribution ◽  
Vldl Triglyceride

Although studies have indicated that the small intestine is capable of utilizing endogenous substrates for triglyceride synthesis in the absence of dietary lipid, the importance of the endogenous contribution to total intestinal triglyceride production during absorption has not yet been defined. In this study we have examined the quantitative contribution of endogenous triglyceride production during different luminal lipid loads. By use of a mesenteric lymph fistula rat model with total parenteral nutritional support, mesenteric lymphatic triglyceride transport was investigated. Our results indicate that, during absorption, a substantial fraction (greater than 50%) of total triglyceride is derived from endogenous sources. Increased luminal fatty acid loads lead to an increase in both endogenous and exogenous triglyceride production. Incorporation of luminally infused oleic acid into triglyceride carried by chylomicrons is dependent on the luminal fatty acid load, while incorporation of oleic acid into very low-density lipoprotein (VLDL) triglyceride is saturable. We conclude that both chylomicron and VLDL are involved in transporting triglyceride derived from both endogenous and exogenous sources. The different patterns in the partition of endogenous and exogenous triglyceride into chylomicrons and VLDL suggest that these two lipid-carrying lipoproteins are probably packaged differently in the small intestine.

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.

scholarly journals ChREBP Rather than SHP Regulates Hepatic VLDL Secretion

2018 ◽  
Author(s):  
Hiroyuki Niwa ◽  
Katsumi Iizuka ◽  
Takehiro Kato ◽  
Wudeluhu Wu ◽  
Hiromi Tsuchida ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Microsomal Triglyceride Transfer Protein ◽  
Wild Type ◽  
Kinase Gene ◽  
Protein Levels ◽  
Vldl Particle ◽  
Vldl Secretion ◽  
Element Binding Protein ◽  
Rat Primary Hepatocytes

The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively. However, Mttp induction by ChREBP was much more potent than suppression by SHP. Promoter assays of Mttp and the liver type pyruvate kinase gene revealed that SHP and ChREBP did not affect the transactivity of each other. Mttp mRNA and protein levels of Shp/– mice were similar to those of wild-type; however, those of Chrebp–/–Shp–/– and Chrebp–/– mice were much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp–/–- mice were similar to wild-type, but were much lower in Chrebp–/– and Chrebp–/–Shp–/–- mice. These findings suggested that ChREBP rather than SHP regulates VLDL secretion and that ChREBP and SHP do not affect the transactivities of each other.

scholarly journals Very-low-density-lipoprotein secretion by isolated hepatocytes of fat-fed rats

1981 ◽  
Vol 198 (2) ◽  
pp. 373-377 ◽  
Author(s):  
A D Kalopissis ◽  
S Griglio ◽  
M I Malewiak ◽  
R Rozen ◽  
X L Liepvre
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Isolated Hepatocytes ◽  
Low Density Lipoproteins ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Lipoprotein Secretion ◽  
Fat Feeding

The very-low-density-lipoprotein secretion rate of isolated hepatocytes obtained from rats fed a high-fat diet was half that of cells from control animals. In fat-fed rats, the initial cellular uptake of [l-14C]oleate in vitro was decreased by 25%, its esterification to triacylglycerols and phospholipids by 50% and its incorporation into very-low-density-lipoprotein triacylglycerols by 70%. Exogenous oleate was not the main precursor of very-low-density lipoproteins in these animals. Lipogenesis, a minor source of very-low-density lipoproteins with the control diet in our experimental conditions, was inhibited by 84% after fat-feeding. A short-term inhibition of lipogenesis in vitro did not result in a decrease in very-low-density-lipoprotein secretion rate. The results suggest that fat-feeding decreased availability of exogenous as well as endogenous fatty acids for synthesis of very-low-density lipoproteins.

Sign in / Sign up

Export Citation Format

Share Document