Genomes and Genes
Summary: A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues.
- Fabbrini E, Mohammed B, Magkos F, Korenblat K, Patterson B, Klein S. Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology. 2008;134:424-31 pubmed publisher..Fatty acids derived from nonsystemic sources are responsible for the increase in VLDL-TG secretion. However, the increase in hepatic TG export is not adequate to normalize IHTG content. ..
- Barrows B, Parks E. Contributions of different fatty acid sources to very low-density lipoprotein-triacylglycerol in the fasted and fed states. J Clin Endocrinol Metab. 2006;91:1446-52 pubmed
- Chong M, Fielding B, Frayn K. Mechanisms for the acute effect of fructose on postprandial lipemia. Am J Clin Nutr. 2007;85:1511-20 pubmed..The contribution of de novo lipogenesis to fructose-induced hypertriacylglycerolemia is small, but its effect on altering the partitioning of fatty acids toward esterification may be considerable. ..
- Chan D, Nguyen M, Watts G, Barrett P. Plasma apolipoprotein C-III transport in centrally obese men: associations with very low-density lipoprotein apolipoprotein B and high-density lipoprotein apolipoprotein A-I metabolism. J Clin Endocrinol Metab. 2008;93:557-64 pubmed..These defects are associated with disturbances in VLDL-apoB and HDL-apoA-I metabolism. ..
- Nguyen M, Chan D, Dwyer K, Bolitho P, Watts G, Barrett P. Use of Intralipid for kinetic analysis of HDL apoC-III: evidence for a homogeneous kinetic pool of apoC-III in plasma. J Lipid Res. 2006;47:1274-80 pubmed
- Millar J, Stone S, Tietge U, Tow B, Billheimer J, Wong J, et al. Short-term overexpression of DGAT1 or DGAT2 increases hepatic triglyceride but not VLDL triglyceride or apoB production. J Lipid Res. 2006;47:2297-305 pubmed..In the presence of adequate cytoplasmic lipid stores, factors other than triglyceride synthesis are rate-limiting for VLDL production. ..
- Heath R, Karpe F, Milne R, Burdge G, Wootton S, Frayn K. Dietary fatty acids make a rapid and substantial contribution to VLDL-triacylglycerol in the fed state. Am J Physiol Endocrinol Metab. 2007;292:E732-9 pubmed..We conclude that there is rapid flux of fatty acids from the diet into endogenous pools. Further study of these processes may open up new targets for intervention to reduce VLDL-TG concentrations and postprandial lipemia. ..
- Peter A, Cegan A, Wagner S, Lehmann R, Stefan N, Konigsrainer A, et al. Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression can be estimated from plasma VLDL fatty acid ratios. Clin Chem. 2009;55:2113-20 pubmed publisher..We demonstrated for the first time that hepatic SCD1 expression can be estimated noninvasively from routine blood samples by measuring the SCD1 activity index in fasting plasma VLDL. ..
- Vedala A, Wang W, Neese R, Christiansen M, Hellerstein M. Delayed secretory pathway contributions to VLDL-triglycerides from plasma NEFA, diet, and de novo lipogenesis in humans. J Lipid Res. 2006;47:2562-74 pubmed..The turnover time and sources of this pool differ in diabetic HPTG and nondiabetic HPTG, with potential therapeutic implications. ..
- Al Shayji I, Gill J, Cooney J, Siddiqui S, Caslake M. Development of a novel method to determine very low density lipoprotein kinetics. J Lipid Res. 2007;48:2086-95 pubmed..05). The protocol is relatively quick, inexpensive, and transferable to nonspecialist laboratories. ..
- Duval C, Muller M, Kersten S. PPARalpha and dyslipidemia. Biochim Biophys Acta. 2007;1771:961-71 pubmed
- Hodson L, McQuaid S, Karpe F, Frayn K, Fielding B. Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate. Am J Physiol Endocrinol Metab. 2009;296:E64-71 pubmed publisher..The marked rapid incorporation of linoleate from a single meal into blood PL fractions may have functional consequences such as maintenance of membrane fluidity and may explain why linoleate is a useful biomarker of dietary intake. ..
- Mandard S, Zandbergen F, van Straten E, Wahli W, Kuipers F, Muller M, et al. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity. J Biol Chem. 2006;281:934-44 pubmed..Our data indicate that disturbances in FIAF signaling might be involved in dyslipidemia. ..
- Jackson K, Maitin V, Leake D, Yaqoob P, Williams C. Saturated fat-induced changes in Sf 60-400 particle composition reduces uptake of LDL by HepG2 cells. J Lipid Res. 2006;47:393-403 pubmed..008). In conclusion, these findings suggest an alternative or additional mechanism whereby acute fat ingestion can influence LDL clearance via competitive apoE-dependent effects of TRL on the LDL receptor. ..
- Chong M, Hodson L, Bickerton A, Roberts R, Neville M, Karpe F, et al. Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr. 2008;87:817-23 pubmed..02). Expression of lipogenic genes in subcutaneous adipose tissue was not significantly affected by diet. Parallel activation of DNL and SCD was found after a short period of HC feeding. ..
- Gormsen L, Nellemann B, Sørensen L, Jensen M, Christiansen J, Nielsen S. Impact of body composition on very-low-density lipoprotein-triglycerides kinetics. Am J Physiol Endocrinol Metab. 2009;296:E165-73 pubmed publisher..We found that elevated VLDL-TG production without concomitant increased clearance via oxidation and adipose tissue redeposition contributes to hypertriglyceridemia in UBO women. ..
- Palacios L, Ochoa B, Gómez Lechón M, Castell J, Fresnedo O. Overexpression of SND p102, a rat homologue of p100 coactivator, promotes the secretion of lipoprotein phospholipids in primary hepatocytes. Biochim Biophys Acta. 2006;1761:698-708 pubmed..Collectively, the results suggest a specific, positive association of SND p102 and phospholipid release in lipoprotein particles in hepatocytes. ..
- Yao H, Ye J. Long chain acyl-CoA synthetase 3-mediated phosphatidylcholine synthesis is required for assembly of very low density lipoproteins in human hepatoma Huh7 cells. J Biol Chem. 2008;283:849-54 pubmed..Treatment of cells with small interfering RNA targeting ACSL3 also inhibited secretion of HCV from Huh7-derived cells. These results identify ACSL3 as a new enzymatic target to limit VLDL secretion and HCV infection. ..
- Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest. 2008;118:829-38 pubmed publisher..This review discusses recent advances in the field. ..
- Nellemann B, Gormsen L, Christiansen J, Jensen M, Nielsen S. Postabsorptive VLDL-TG fatty acid storage in adipose tissue in lean and obese women. Obesity (Silver Spring). 2010;18:1304-11 pubmed publisher..We suggest that the differences in VLDL-TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL activity. ..
- Wood R, Volek J, Liu Y, Shachter N, Contois J, Fernandez M. Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men. J Nutr. 2006;136:384-9 pubmed..01). We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease. ..
- Adiels M, Olofsson S, Taskinen M, Boren J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28:1225-36 pubmed publisher..Finally, we briefly discuss current treatments for lipid management of dyslipidemia and potential future therapeutic targets. ..
- Hodson L, Bickerton A, McQuaid S, Roberts R, Karpe F, Frayn K, et al. The contribution of splanchnic fat to VLDL triglyceride is greater in insulin-resistant than insulin-sensitive men and women: studies in the postprandial state. Diabetes. 2007;56:2433-41 pubmed..In the postprandial period, the only sources of fatty acids for VLDL TG production to differ in the insulin-resistant compared with the insulin-sensitive men are those derived from splanchnic sources. ..
- Li L, Stillemark Billton P, Beck C, Boström P, Andersson L, Rutberg M, et al. Epigallocatechin gallate increases the formation of cytosolic lipid droplets and decreases the secretion of apoB-100 VLDL. J Lipid Res. 2006;47:67-77 pubmed..Our results also indicate that the accumulation of lipids in the cytosol is not always associated with increased secretion of VLDL. ..
- Han S, Liang C, Westerterp M, Senokuchi T, Welch C, Wang Q, et al. Hepatic insulin signaling regulates VLDL secretion and atherogenesis in mice. J Clin Invest. 2009;119:1029-41 pubmed publisher..These findings suggest a dual action of hepatic IR on lipoprotein levels, in which the ability to increase VLDL apoB and lipid secretion via AKT/GSK is offset by upregulation of Ldlr. ..
- Huang H, Sun F, Owen D, Li W, Chen Y, Gale M, et al. Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc Natl Acad Sci U S A. 2007;104:5848-53 pubmed..These results provide a possible explanation for the restriction of HCV production to the liver and suggest new cellular targets for treatment of HCV infection. ..
- Seshadri P, Iqbal N, Stern L, Williams M, Chicano K, Daily D, et al. A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. Am J Med. 2004;117:398-405 pubmed..Both diets had similar effects on LDL and HDL subfractions. ..
- Merkel M, Loeffler B, Kluger M, Fabig N, Geppert G, Pennacchio L, et al. Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase. J Biol Chem. 2005;280:21553-60 pubmed..A direct interaction between LPL and apoAV was found by ligand blotting. It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycan-bound LPL for lipolysis. ..
- Schaap F, Rensen P, Voshol P, Vrins C, van der Vliet H, Chamuleau R, et al. ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis. J Biol Chem. 2004;279:27941-7 pubmed..From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins. ..
- Asp L, Magnusson B, Rutberg M, Li L, Boren J, Olofsson S. Role of ADP ribosylation factor 1 in the assembly and secretion of ApoB-100-containing lipoproteins. Arterioscler Thromb Vasc Biol. 2005;25:566-70 pubmed..Overexpression of ARF1 increased the assembly of VLDL 2 but not of VLDL 1, whose production was dependent on both anterograde transport and the availability of fatty acids. ..
- Avramoglu R, Adeli K. Hepatic regulation of apolipoprotein B. Rev Endocr Metab Disord. 2004;5:293-301 pubmed
- Stillemark Billton P, Beck C, Boren J, Olofsson S. Relation of the size and intracellular sorting of apoB to the formation of VLDL 1 and VLDL 2. J Lipid Res. 2005;46:104-14 pubmed..We propose that the dense apoB-100 intracellular particle is converted to LDL-VLDL 2 by size-dependent lipidation. LDL-VLDL 2 is secreted or converted to VLDL 1 by the uptake of the major amount of triglycerides. ..
- Larsson S, Skogsberg J, Björkegren J. The low density lipoprotein receptor prevents secretion of dense apoB100-containing lipoproteins from the liver. J Biol Chem. 2004;279:831-6 pubmed..In addition, these results suggest that very low levels of MTP are insufficient to mediate the second step but sufficient for the first step of VLDL assembly. ..
- Okazaki M, Usui S, Ishigami M, Sakai N, Nakamura T, Matsuzawa Y, et al. Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profile in high-performance liquid chromatography. Arterioscler Thromb Vasc Biol. 2005;25:578-84 pubmed..These findings indicate that this simple high-performance liquid chromatography method may be applied for easy detection and evaluation of abnormal distribution of lipoprotein subclasses. ..
- Vegusdal A, Gjøen T, Berge R, Thomassen M, Ruyter B. Effect of 18:1n-9, 20:5n-3, and 22:6n-3 on lipid accumulation and secretion by Atlantic salmon hepatocytes. Lipids. 2005;40:477-86 pubmed..The area occupied by mitochondria was also greater in these cells. The present study shows that dietary FO reduces TAG secretion from salmon hepatocytes and that 20:5n-3 mediates this effect. ..
- Bysted A, Hølmer G, Lund P, Sandstrom B, Tholstrup T. Effect of dietary fatty acids on the postprandial fatty acid composition of triacylglycerol-rich lipoproteins in healthy male subjects. Eur J Clin Nutr. 2005;59:24-34 pubmed..The fatty acid composition in the test fats as well as the positional distributions of these were maintained in the chylomicrons. No specific clearing of chylomicron TAG was observed in relation to time. ..
- Adiels M, Packard C, Caslake M, Stewart P, Soro A, Westerbacka J, et al. A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions. J Lipid Res. 2005;46:58-67 pubmed..These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver. ..
- Sato K, Cho Y, Tachibana S, Chiba T, Schneider W, Akiba Y. Impairment of VLDL secretion by medium-chain fatty acids in chicken primary hepatocytes is affected by the chain length. J Nutr. 2005;135:1636-41 pubmed
- de Fourmestraux V, Neubauer H, Poussin C, Farmer P, Falquet L, Burcelin R, et al. Transcript profiling suggests that differential metabolic adaptation of mice to a high fat diet is associated with changes in liver to muscle lipid fluxes. J Biol Chem. 2004;279:50743-53 pubmed..Finally, gene classifiers could be established that were characteristic of each metabolic phenotype. Together, these data suggest that epigenetic mechanisms influence gene expression patterns and metabolic fates. ..
- Cohn J, Patterson B, Uffelman K, Davignon J, Steiner G. Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensiti. J Clin Endocrinol Metab. 2004;89:3949-55 pubmed
- Gibbons G, Wiggins D, Brown A, Hebbachi A. Synthesis and function of hepatic very-low-density lipoprotein. Biochem Soc Trans. 2004;32:59-64 pubmed
- Ng T, Watts G, Farvid M, Chan D, Barrett P. Adipocytokines and VLDL metabolism: independent regulatory effects of adiponectin, insulin resistance, and fat compartments on VLDL apolipoprotein B-100 kinetics?. Diabetes. 2005;54:795-802 pubmed..Total body fat may also independently determine the rate of VLDL catabolism, but leptin, resistin, IL-6, and TNF-alpha do not have a significant effect in regulating apoB kinetics. ..
- Festa A, Williams K, Hanley A, Otvos J, Goff D, Wagenknecht L, et al. Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the Insulin Resistance Atherosclerosis Study. Circulation. 2005;111:3465-72 pubmed..These findings extend previous work indicating a proatherogenic state in healthy, nondiabetic subjects who subsequently develop diabetes. ..
- Bederman I, Reszko A, Kasumov T, David F, Wasserman D, Kelleher J, et al. Zonation of labeling of lipogenic acetyl-CoA across the liver: implications for studies of lipogenesis by mass isotopomer analysis. J Biol Chem. 2004;279:43207-16 pubmed..R., Kasumov, T., Reszko, A. E., David, F., Brunengraber, H., and Kelleher, J. K. (2004) J. Biol. Chem. 279, 43217-43226). ..
- Pan M, Cederbaum A, Zhang Y, Ginsberg H, Williams K, Fisher E. Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production. J Clin Invest. 2004;113:1277-87 pubmed
- Minehira Castelli K, Leonard S, Walker Q, Traber M, Young S. Absence of VLDL secretion does not affect alpha-tocopherol content in peripheral tissues. J Lipid Res. 2006;47:1733-8 pubmed..We conclude that the absence of VLDL secretion has little effect on the stores of alpha-tocopherol in peripheral tissues, at least in the mouse. ..
- Brouwers M, Van Greevenbroek M, Bilderbeek Beckers M, Robertus Teunissen M, van der Kallen C, Stehouwer C, et al. Fatty liver--based identification of two distinct hypertriglyceridemic subgroups in familial combined hyperlipidemia. Metabolism. 2007;56:1311-7 pubmed
- Olofsson S, Boström P, Andersson L, Rutberg M, Perman J, Boren J. Lipid droplets as dynamic organelles connecting storage and efflux of lipids. Biochim Biophys Acta. 2009;1791:448-58 pubmed publisher..Finally, we briefly review the importance of lipid droplets in the development of insulin resistance and atherosclerosis...
- López Soldado I, Avella M, Botham K. Suppression of VLDL secretion by cultured hepatocytes incubated with chylomicron remnants enriched in n-3 polyunsaturated fatty acids is regulated by hepatic nuclear factor-4alpha. Biochim Biophys Acta. 2009;1791:1181-9 pubmed publisher..These findings suggest that the direct suppression of VLDL secretion by dietary n-3 PUFA delivered to the liver in CMR is mediated via decreased expression of HNF-4alpha. ..
- Ohsaki Y, Cheng J, Fujita A, Tokumoto T, Fujimoto T. Cytoplasmic lipid droplets are sites of convergence of proteasomal and autophagic degradation of apolipoprotein B. Mol Biol Cell. 2006;17:2674-83 pubmed..These observations indicate that both proteasomal and autophagy/lysosomal degradation of ApoB occur around CLDs and that the CLD surface functions as a unique platform for convergence of the two pathways. ..
- Ota T, Gayet C, Ginsberg H. Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. J Clin Invest. 2008;118:316-32 pubmed..These results suggest that excessive ER stress in response to increased hepatic lipids may decrease the ability of the liver to secrete triglycerides by limiting apoB secretion, potentially worsening steatosis. ..
- Chen Z, Newberry E, Norris J, Xie Y, Luo J, Kennedy S, et al. ApoB100 is required for increased VLDL-triglyceride secretion by microsomal triglyceride transfer protein in ob/ob mice. J Lipid Res. 2008;49:2013-22 pubmed publisher..These findings demonstrate that Ad-mMTP increases murine hepatic VLDL-TG secretion only in the apoB100 background, and even then only in situations with either increased hepatic TG accumulation or increased apoB100 expression. ..