1932

Abstract

Recent advances in human genetics, together with a substantial body of epidemiological, preclinical and clinical trial evidence, strongly support a causal relationship between triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular disease. Consequently, the secretion and metabolism of TRLs have a significant impact on cardiovascular health. This knowledge underscores the importance of understanding the molecular mechanisms and regulation of very-low-density lipoprotein (VLDL) and chylomicron biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL, leading to many ground-breaking molecular insights. Furthermore, the identification of molecular control mechanisms related to triglyceride metabolism has greatly advanced our understanding of the complex metabolism of TRLs. In this review, we explore recent advances in the assembly, secretion, and metabolism of TRLs. We also discuss available treatment strategies for hypertriglyceridemia.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-062222-020716
2024-08-29
2025-02-10
Loading full text...

Full text loading...

/deliver/fulltext/nutr/44/1/annurev-nutr-062222-020716.html?itemId=/content/journals/10.1146/annurev-nutr-062222-020716&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Adiels M, Borén J, Caslake MJ, Stewart P, Soro A, et al. 2005.. Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia. . Arterioscler. Thromb. Vasc. Biol. 25::1697703
    [Crossref] [Google Scholar]
  2. 2.
    Adiels M, Olofsson SO, Taskinen MR, Borén J. 2006.. Diabetic dyslipidaemia. . Curr. Opin. Lipidol. 17::23846
    [Crossref] [Google Scholar]
  3. 3.
    Adiels M, Olofsson SO, Taskinen MR, Borén J. 2008.. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. . Arterioscler. Thromb. Vasc. Biol. 28::122536
    [Crossref] [Google Scholar]
  4. 4.
    Adiels M, Packard C, Caslake MJ, Stewart P, Soro A, et al. 2005.. A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions. . J. Lipid Res. 46::5867
    [Crossref] [Google Scholar]
  5. 5.
    Adiels M, Taskinen MR, Packard C, Caslake MJ, Soro-Paavonen A, et al. 2006.. Overproduction of large VLDL particles is driven by increased liver fat content in man. . Diabetologia 49::75565
    [Crossref] [Google Scholar]
  6. 6.
    Adiels M, Westerbacka J, Soro-Paavonen A, Häkkinen A-M, Vehkavaara S, et al. 2007.. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. . Diabetologia 50::235665
    [Crossref] [Google Scholar]
  7. 7.
    Alexander CA, Hamilton RL, Havel RJ. 1976.. Subcellular localization of B apoprotein of plasma lipoproteins in rat liver. . J. Cell Biol. 69::24163
    [Crossref] [Google Scholar]
  8. 8.
    Allister EM, Borradaile NM, Edwards JY, Huff MW. 2005.. Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein B100 secretion by the citrus flavonoid naringenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes. . Diabetes 54::167683
    [Crossref] [Google Scholar]
  9. 9.
    Asp L, Claesson C, Borén J, Olofsson SO. 2000.. ADP-ribosylation factor 1 and its activation of phospholipase D are important for the assembly of very low density lipoproteins. . J. Biol. Chem. 275::2628592
    [Crossref] [Google Scholar]
  10. 10.
    Asp L, Magnusson B, Rutberg M, Li L, Borén J, Olofsson SO. 2005.. Role of ADP ribosylation factor 1 in the assembly and secretion of ApoB-100-containing lipoproteins. . Arterioscler. Thromb. Vasc. Biol. 25::56670
    [Crossref] [Google Scholar]
  11. 11.
    Balling M, Afzal S, Varbo A, Langsted A, Davey Smith G, Nordestgaard BG. 2020.. VLDL cholesterol accounts for one-half of the risk of myocardial infarction associated with apoB-containing lipoproteins. . J. Am. Coll. Cardiol. 76::272535
    [Crossref] [Google Scholar]
  12. 12.
    Berberich AJ, Hegele RA. 2022.. A modern approach to dyslipidemia. . Endocrine Rev. 43::61153
    [Crossref] [Google Scholar]
  13. 13.
    Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, et al. 2019.. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. . N. Engl. J. Med. 380::1122
    [Crossref] [Google Scholar]
  14. 14.
    Bjornson E, Adiels M, Taskinen MR, Burgess S, Rawshani A, et al. 2023.. Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study. . Eur. Heart J. 44::418695
    [Crossref] [Google Scholar]
  15. 15.
    Bjornson E, Packard CJ, Adiels M, Andersson L, Matikainen N, et al. 2020.. Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects. . J. Intern. Med. 288::42238
    [Crossref] [Google Scholar]
  16. 16.
    Bjornson E, Packard CJ, Adiels M, Andersson L, Matikainen N, et al. 2019.. Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics. . J. Intern. Med. 285::56277
    [Crossref] [Google Scholar]
  17. 17.
    Borén J, Adiels M, Bjornson E, Matikainen N, Soderlund S, et al. 2022.. Effects of PNPLA3 I148M on hepatic lipid and very-low-density lipoprotein metabolism in humans. . J. Intern. Med. 291::21823
    [Crossref] [Google Scholar]
  18. 18.
    Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, et al. 2020.. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. . Eur. Heart J. 41::231330
    [Crossref] [Google Scholar]
  19. 19.
    Borén J, Packard CJ, Taskinen MR. 2020.. The roles of apoC-III on the metabolism of triglyceride-rich lipoproteins in humans. . Front. Endocrinol. 11::474
    [Crossref] [Google Scholar]
  20. 20.
    Borén J, Taskinen MR, Bjornson E, Packard CJ. 2022.. Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia. . Nat. Rev. Cardiol. 19::57792
    [Crossref] [Google Scholar]
  21. 21.
    Borén J, Watts GF, Adiels M, Soderlund S, Chan DC, et al. 2015.. Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: multicenter tracer kinetic study. . Arterioscler. Thromb. Vasc. Biol. 35::221824
    [Crossref] [Google Scholar]
  22. 22.
    Borén J, Wettesten M, Sjoberg A, Thorlin T, Bondjers G, et al. 1990.. The assembly and secretion of apoB 100 containing lipoproteins in Hep G2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly. . J. Biol. Chem. 265::1055664
    [Crossref] [Google Scholar]
  23. 23.
    Boström K, Borén J, Wettesten M, Sjöberg A, Bondjers G, et al. 1988.. Studies on the assembly of apo B-100-containing lipoproteins in HepG2 cells. . J. Biol. Chem. 263::443442
    [Crossref] [Google Scholar]
  24. 24.
    Boström K, Wettesten M, Borén J, Bondjers G, Wiklund O, Olofsson SO. 1986.. Pulse-chase studies of the synthesis and intracellular transport of apolipoprotein B-100 in Hep G2 cells. . J. Biol. Chem. 261::138006
    [Crossref] [Google Scholar]
  25. 25.
    Boström P, Andersson L, Rutberg M, Perman J, Lidberg U, et al. 2007.. SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity. . Nat. Cell Biol. 9::128693
    [Crossref] [Google Scholar]
  26. 26.
    Brodsky JL. 2007.. The protective and destructive roles played by molecular chaperones during ERAD (endoplasmic-reticulum-associated degradation). . Biochem. J. 404::35363
    [Crossref] [Google Scholar]
  27. 27.
    Butkinaree C, Guo L, Ramkhelawon B, Wanschel A, Brodsky JL, et al. 2014.. A regulator of secretory vesicle size, Kelch-like protein 12, facilitates the secretion of apolipoprotein B100 and very-low-density lipoproteins—brief report. . Arterioscler. Thromb. Vasc. Biol. 34::25154
    [Crossref] [Google Scholar]
  28. 28.
    Carr A, Samaras K, Burton S, Law M, Freund J, et al. 1998.. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. . AIDS 12::F5158
    [Crossref] [Google Scholar]
  29. 29.
    Cartwright IJ, Plonne D, Higgins JA. 2000.. Intracellular events in the assembly of chylomicrons in rabbit enterocytes. . J. Lipid Res. 41::172839
    [Crossref] [Google Scholar]
  30. 30.
    Chavez-Jauregui RN, Mattes RD, Parks EJ. 2010.. Dynamics of fat absorption and effect of sham feeding on postprandial lipema. . Gastroenterology 139::153848
    [Crossref] [Google Scholar]
  31. 31.
    Chuck SL, Yao Z, Blackhart BD, McCarthy BJ, Lingappa VR. 1990.. New variation on the translocation of proteins during early biogenesis of apolipoprotein B. . Nature 346::38285
    [Crossref] [Google Scholar]
  32. 32.
    Conlon DM, Schneider CV, Ko YA, Rodrigues A, Guo K, et al. 2022.. Sortilin restricts secretion of apolipoprotein B-100 by hepatocytes under stressed but not basal conditions. . J. Clin. Investig. 132:(6):e14433
    [Crossref] [Google Scholar]
  33. 33.
    Dai W, Zhang H, Lund H, Zhang Z, Castleberry M, et al. 2023.. Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes. . Science 381::eadh5207
    [Crossref] [Google Scholar]
  34. 34.
    Das Pradhan A, Glynn RJ, Fruchart J-C, MacFadyen JG, Zaharris ES, et al. 2022.. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. . N. Engl. J. Med. 387::192334
    [Crossref] [Google Scholar]
  35. 35.
    Dashti N, Gandhi M, Liu X, Lin X, Segrest JP. 2002.. The N-terminal 1000 residues of apolipoprotein B associate with microsomal triglyceride transfer protein to create a lipid transfer pocket required for lipoprotein assembly. . Biochemistry 41::697887
    [Crossref] [Google Scholar]
  36. 36.
    Doi T, Langsted A, Nordestgaard BG. 2022.. Elevated remnant cholesterol reclassifies risk of ischemic heart disease and myocardial infarction. . J. Am. Coll. Cardiol. 79::238397
    [Crossref] [Google Scholar]
  37. 37.
    Donaldson JG, Jackson CL. 2011.. ARF family G proteins and their regulators: roles in membrane transport, development and disease. . Nat. Rev. Mol. Cell Biol. 12::36275
    [Crossref] [Google Scholar]
  38. 38.
    Dongiovanni P, Petta S, Maglio C, Fracanzani AL, Pipitone R, et al. 2015.. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. . Hepatology 61::50614
    [Crossref] [Google Scholar]
  39. 39.
    Du X, Stoops JD, Mertz JR, Stanley CM, Dixon JL. 1998.. Identification of two regions in apolipoprotein B100 that are exposed on the cytosolic side of the endoplasmic reticulum membrane. . J. Cell Biol. 141::58599
    [Crossref] [Google Scholar]
  40. 40.
    Fielding BA, Reid G, Grady M, Humphreys SM, Evans K, Frayn KN. 2000.. Ethanol with a mixed meal increases postprandial triacylglycerol but decreases postprandial non-esterified fatty acid concentrations. . Br. J. Nutr. 83::597604
    [Crossref] [Google Scholar]
  41. 41.
    Fisher EA, Ginsberg HN. 2002.. Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. . J. Biol. Chem. 277::1737780
    [Crossref] [Google Scholar]
  42. 42.
    Fisher EA, Khanna NA, McLeod RS. 2011.. Ubiquitination regulates the assembly of VLDL in HepG2 cells and is the committing step of the apoB-100 ERAD pathway. . J. Lipid Res. 52::117080
    [Crossref] [Google Scholar]
  43. 43.
    Furukawa S, Sakata N, Ginsberg H, Dixon J. 1992.. Studies of the sites of intracellular degradation of apolipoprotein B in Hep G2 cells. . J. Biol. Chem. 267::2263038
    [Crossref] [Google Scholar]
  44. 44.
    Ginsberg HN, Fisher EA. 2009.. The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism. . J. Lipid Res. 50:(Suppl.):S16266
    [Crossref] [Google Scholar]
  45. 45.
    Ginsberg HN, Goldberg IJ. 2023.. Broadening the scope of dyslipidemia therapy by targeting APOC3 (apolipoprotein C3) and ANGPTL3 (angiopoietin-like protein 3). . Arterioscler. Thromb. Vasc. Biol. 43::38898
    [Crossref] [Google Scholar]
  46. 46.
    Ginsberg HN, Packard CJ, Chapman MJ, Borén J, Aguilar-Salinas CA, et al. 2021.. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society. . Eur. Heart J. 42::4791806
    [Crossref] [Google Scholar]
  47. 47.
    Goldberg IJ, Gjini J, Fisher EA. 2022.. Big fish or no fish; eicosapentaenoic acid and cardiovascular disease. . Endocrinol. Metab. Clin. North Am. 51::62533
    [Crossref] [Google Scholar]
  48. 48.
    Gordon DA, Jamil H, Gregg RE, Olofsson SO, Borén J. 1996.. Inhibition of the microsomal triglyceride transfer protein blocks the first step of apolipoprotein B lipoprotein assembly but not the addition of bulk core lipids in the second step. . J. Biol. Chem. 271::3304753
    [Crossref] [Google Scholar]
  49. 49.
    Gordon DA, Jamil H, Sharp D, Mullaney D, Yao Z, et al. 1994.. Secretion of apolipoprotein B-containing lipoproteins from HeLa cells is dependent on expression of the microsomal triglyceride transfer protein and is regulated by lipid availability. . PNAS 91::762832
    [Crossref] [Google Scholar]
  50. 50.
    Gouni-Berthold I, Berthold HK. 2015.. Mipomersen and lomitapide: two new drugs for the treatment of homozygous familial hypercholesterolemia. . Atheroscler. Suppl. 18::2834
    [Crossref] [Google Scholar]
  51. 51.
    Guan M, Qu L, Tan W, Chen L, Wong CW. 2011.. Hepatocyte nuclear factor-4 alpha regulates liver triglyceride metabolism in part through secreted phospholipase A2 GXIIB. . Hepatology 53::45866
    [Crossref] [Google Scholar]
  52. 52.
    Hsu CC, Kanter JE, Kothari V, Bornfeldt KE. 2023.. Quartet of APOCs and the different roles they play in diabetes. . Arterioscler. Thromb. Vasc. Biol. 43::112433
    [Crossref] [Google Scholar]
  53. 53.
    Huang D, Xu B, Liu L, Wu L, Zhu Y, et al. 2021.. TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis. . Cell Metab. 33::165570.e8
    [Crossref] [Google Scholar]
  54. 54.
    Huang Y, Mahley RW. 2014.. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases. . Neurobiol. Dis. 72:(Part A):312
    [Crossref] [Google Scholar]
  55. 55.
    James R, Martin B, Pometta D, Fruchart J, Duriez P, et al. 1989.. Apolipoprotein B metabolism in homozygous familial hypercholesterolemia. . J. Lipid Res. 30::15969
    [Crossref] [Google Scholar]
  56. 56.
    Jiang X, Fulte S, Deng F, Chen S, Xie Y, et al. 2022.. Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis. . J. Hepatol. 77::61931
    [Crossref] [Google Scholar]
  57. 57.
    Johansen , Afzal S, Vedel-Krogh S, Nielsen SF, Smith GD, Nordestgaard BG. 2023.. From plasma triglycerides to triglyceride metabolism: effects on mortality in the Copenhagen General Population Study. . Eur. Heart J. 44::417482
    [Crossref] [Google Scholar]
  58. 58.
    Khan NA, Besnard P. 2009.. Oro-sensory perception of dietary lipids: new insights into the fat taste transduction. . Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1791::14955
    [Crossref] [Google Scholar]
  59. 59.
    Khetarpal SA, Vitali C, Levin MG, Klarin D, Park J, et al. 2021.. Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins. . PLOS Genet. 17::e1009802
    [Crossref] [Google Scholar]
  60. 60.
    Kirchhausen T. 2000.. Three ways to make a vesicle. . Nat. Rev. Mol. Cell Biol. 1::18798
    [Crossref] [Google Scholar]
  61. 61.
    Kiss RS, Nilsson T. 2014.. Rab proteins implicated in lipid storage and mobilization. . J. Biomed. Res. 28::16977
    [Crossref] [Google Scholar]
  62. 62.
    Krahmer N, Guo Y, Wilfling F, Hilger M, Lingrell S, et al. 2011.. Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. . Cell Metab. 14::50415
    [Crossref] [Google Scholar]
  63. 63.
    Lam TK, Gutierrez-Juarez R, Pocai A, Bhanot S, Tso P, et al. 2007.. Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. . Nat. Med. 13::17180
    [Crossref] [Google Scholar]
  64. 64.
    Lambert JE, Parks EJ. 2012.. Postprandial metabolism of meal triglyceride in humans. . Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1821::72126
    [Crossref] [Google Scholar]
  65. 65.
    Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. 2020.. Clinical review on triglycerides. . Eur. Heart J. 41::99109c
    [Crossref] [Google Scholar]
  66. 66.
    Lawler PR, Kotrri G, Koh M, Goodman SG, Farkouh ME, et al. 2020.. Real-world risk of cardiovascular outcomes associated with hypertriglyceridaemia among individuals with atherosclerotic cardiovascular disease and potential eligibility for emerging therapies. . Eur. Heart J. 41::8694
    [Crossref] [Google Scholar]
  67. 67.
    Levy E, Beaulieu JF, Spahis S. 2021.. From congenital disorders of fat malabsorption to understanding intra-enterocyte mechanisms behind chylomicron assembly and secretion. . Front. Physiol. 12::629222
    [Crossref] [Google Scholar]
  68. 68.
    Levy E, Spahis S, Garofalo C, Marcil V, Montoudis A, et al. 2014.. Sar1b transgenic male mice are more susceptible to high-fat diet-induced obesity, insulin insensitivity and intestinal chylomicron overproduction. . J. Nutr. Biochem. 25::54048
    [Crossref] [Google Scholar]
  69. 69.
    Lewis GF, Hegele RA. 2022.. Effective, disease-modifying, clinical approaches to patients with mild-to-moderate hypertriglyceridaemia. . Lancet Diabetes Endocrinol. 10::14248
    [Crossref] [Google Scholar]
  70. 70.
    Lewis GF, Uffelman KD, Szeto LW, Steiner G. 1993.. Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. . Diabetes 42::83342
    [Crossref] [Google Scholar]
  71. 71.
    Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. 1995.. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. . J. Clin. Investig. 95::15866
    [Crossref] [Google Scholar]
  72. 72.
    Li BT, Sun M, Li YF, Wang JQ, Zhou ZM, et al. 2020.. Disruption of the ERLIN-TM6SF2-APOB complex destabilizes APOB and contributes to non-alcoholic fatty liver disease. . PLOS Genet. 16::e1008955
    [Crossref] [Google Scholar]
  73. 73.
    Li YE, Wang Y, Du X, Zhang T, Mak HY, et al. 2021.. TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine. . J. Cell Biol. 220::e202103105
    [Crossref] [Google Scholar]
  74. 74.
    Lin H, Wang L, Liu Z, Long K, Kong M, et al. 2022.. Hepatic MDM2 causes metabolic associated fatty liver disease by blocking triglyceride-VLDL secretion via apoB degradation. . Adv. Sci. 9::e2200742
    [Crossref] [Google Scholar]
  75. 75.
    Luna-Castillo KP, Olivares-Ochoa XC, Hernández-Ruiz RG, Llamas-Covarrubias IM, Rodríguez-Reyes SC, et al. 2022.. The effect of dietary interventions on hypertriglyceridemia: from public health to molecular nutrition evidence. . Nutrients 14::1104
    [Crossref] [Google Scholar]
  76. 76.
    Luukkonen PK, Zhou Y, Haridas PAN, Dwivedi OP, Hyotylainen T, et al. 2017.. Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD. . J. Hepatol. 67::12836
    [Crossref] [Google Scholar]
  77. 77.
    Lv Z, Chu Y, Wang Y. 2015.. HIV protease inhibitors: a review of molecular selectivity and toxicity. . HIV AIDS 7::95104
    [Google Scholar]
  78. 78.
    Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, et al. 2020.. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. . Eur. Heart J. 41::11188
    [Crossref] [Google Scholar]
  79. 79.
    Malmström R, Packard CJ, Caslake M, Bedford D, Stewart P, et al. 1998.. Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in normal subjects. . Diabetes 47::77987
    [Crossref] [Google Scholar]
  80. 80.
    Mansbach CM, Siddiqi SA. 2010.. The biogenesis of chylomicrons. . Annu. Rev. Physiol. 72::31533
    [Crossref] [Google Scholar]
  81. 81.
    Mason RP, Sherratt SC, Eckel RH. 2023.. Omega-3-fatty acids: Do they prevent cardiovascular disease?. Best Pract. Res. Clin. Endocrinol. Metab. 37::101681
    [Crossref] [Google Scholar]
  82. 82.
    Matsuoka K, Orci L, Amherdt M, Bednarek SY, Hamamoto S, et al. 1998.. COPII-coated vesicle formation reconstituted with purified coat proteins and chemically defined liposomes. . Cell 93::26375
    [Crossref] [Google Scholar]
  83. 83.
    McCormick SP, Ng JK, Veniant M, Borén J, Pierotti V, et al. 1996.. Transgenic mice that overexpress mouse apolipoprotein B. Evidence that the DNA sequences controlling intestinal expression of the apolipoprotein B gene are distant from the structural gene. . J. Biol. Chem. 271::1196370
    [Crossref] [Google Scholar]
  84. 84.
    Molk N, Bitenc M, Urlep D, Zerjav Tansek M, Bertok S, et al. 2023.. Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review. . Front. Med. 10::1106441
    [Crossref] [Google Scholar]
  85. 85.
    Montaigne D, Butruille L, Staels B. 2021.. PPAR control of metabolism and cardiovascular functions. . Nat. Rev. Cardiol. 18::80923
    [Crossref] [Google Scholar]
  86. 86.
    Murakami M, Taketomi Y, Sato H, Yamamoto K. 2011.. Secreted phospholipase A2 revisited. . J. Biochem. 150::23355
    [Crossref] [Google Scholar]
  87. 87.
    Neeli I, Siddiqi SA, Siddiqi S, Mahan J, Lagakos WS, et al. 2007.. Liver fatty acid-binding protein initiates budding of pre-chylomicron transport vesicles from intestinal endoplasmic reticulum. . J. Biol. Chem. 282::1797484
    [Crossref] [Google Scholar]
  88. 88.
    Nicholls SJ, Nelson AJ. 2022.. CETP inhibitors: should we continue to pursue this pathway?. Curr. Atheroscler. Rep. 24::91523
    [Crossref] [Google Scholar]
  89. 89.
    Olofsson SO, Borén J. 2005.. Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis. . J. Intern. Med. 258::395410
    [Crossref] [Google Scholar]
  90. 90.
    Olofsson SO, Borén J. 2012.. Apolipoprotein B secretory regulation by degradation. . Arterioscler. Thromb. Vasc. Biol. 32::133438
    [Crossref] [Google Scholar]
  91. 91.
    Olofsson SO, Boström P, Andersson L, Rutberg M, Perman J, Borén J. 2009.. Lipid droplets as dynamic organelles connecting storage and efflux of lipids. . Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1791::44858
    [Crossref] [Google Scholar]
  92. 92.
    Packard CJ. 2017.. Unpacking and understanding the impact of proprotein convertase subtilisin/kexin type 9 inhibitors on apolipoprotein B metabolism. . Circulation 135::36365
    [Crossref] [Google Scholar]
  93. 93.
    Packard CJ, Boren J, Taskinen MR. 2020.. Causes and consequences of hypertriglyceridemia. . Front. Endocrinol. 11::252
    [Crossref] [Google Scholar]
  94. 94.
    Pan X, Hussain MM. 2012.. Gut triglyceride production. . Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1821::72735
    [Crossref] [Google Scholar]
  95. 95.
    Peng H, Chiu TY, Liang YJ, Lee CJ, Liu CS, et al. 2021.. PRAP1 is a novel lipid-binding protein that promotes lipid absorption by facilitating MTTP-mediated lipid transport. . J. Biol. Chem. 296::100052
    [Crossref] [Google Scholar]
  96. 96.
    Peng Y, Zeng Q, Wan L, Ma E, Li H, et al. 2021.. GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity. . Nat. Commun. 12::7004
    [Crossref] [Google Scholar]
  97. 97.
    Phung TL, Roncone A, de Mesy Jensen KL, Sparks CE, Sparks JD. 1997.. Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum. . J. Biol. Chem. 272::30693702
    [Crossref] [Google Scholar]
  98. 98.
    Pocai A, Obici S, Schwartz GJ, Rossetti L. 2005.. A brain-liver circuit regulates glucose homeostasis. . Cell Metab. 1::5361
    [Crossref] [Google Scholar]
  99. 99.
    Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J. 1987.. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. . Cell 50::83140
    [Crossref] [Google Scholar]
  100. 100.
    Prinsen BH, Romijn JA, Bisschop PH, de Barse MM, Barrett PHR, et al. 2003.. Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans. . J. Lipid Res. 44::134148
    [Crossref] [Google Scholar]
  101. 101.
    Quispe R, Sweeney T, Varma B, Agarwala A, Michos ED. 2022.. Recent updates in hypertriglyceridemia management for cardiovascular disease prevention. . Curr. Atheroscler. Rep. 24::76778
    [Crossref] [Google Scholar]
  102. 102.
    Rahim A, Nafi-valencia E, Siddiqi S, Basha R, Runyon CC, Siddiqi SA. 2012.. Proteomic analysis of the very low density lipoprotein (VLDL) transport vesicles. . J. Proteom. 75::222535
    [Crossref] [Google Scholar]
  103. 103.
    Raote I, Saxena S, Malhotra V. 2023.. Sorting and export of proteins at the endoplasmic reticulum. . Cold Spring Harb. Perspect. Biol. 15::a041258
    [Crossref] [Google Scholar]
  104. 104.
    Rustaeus S, Stillemark P, Lindberg K, Gordon D, Olofsson SO. 1998.. The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. . J. Biol. Chem. 273::5196203
    [Crossref] [Google Scholar]
  105. 105.
    Sabesin SM, Clark SB, Holt PR. 1977.. Ultrastructural features of regional differences in chylomicron secretion by rat intestine. . Exp. Mol. Pathol. 26::27789
    [Crossref] [Google Scholar]
  106. 106.
    Sabesin SM, Frase S. 1977.. Electron microscopic studies of the assembly, intracellular transport, and secretion of chylomicrons by rat intestine. . J. Lipid Res. 18::496511
    [Crossref] [Google Scholar]
  107. 107.
    Santos-Baez LS, Ginsberg HN. 2020.. Hypertriglyceridemia—causes, significance, and approaches to therapy. . Front. Endocrinol. 11::616
    [Crossref] [Google Scholar]
  108. 108.
    Santos AJ, Nogueira C, Ortega-Bellido M, Malhotra V. 2016.. TANGO1 and Mia2/cTAGE5 (TALI) cooperate to export bulky pre-chylomicrons/VLDLs from the endoplasmic reticulum. . J. Cell Biol. 213::34354
    [Crossref] [Google Scholar]
  109. 109.
    Segrest JP, Jones MK, De Loof H, Dashti N. 2001.. Structure of apolipoprotein B-100 in low density lipoproteins. . J. Lipid Res. 42::134667
    [Crossref] [Google Scholar]
  110. 110.
    Shen Y, Gu HM, Qin S, Zhang DW. 2023.. Surf4, cargo trafficking, lipid metabolism, and therapeutic implications. . J. Mol. Cell Biol. 14::mjac063
    [Crossref] [Google Scholar]
  111. 111.
    Siddiqi S, Mani AM, Siddiqi SA. 2010.. The identification of the SNARE complex required for the fusion of VLDL-transport vesicle with hepatic cis-Golgi. . Biochem. J. 429::391401
    [Crossref] [Google Scholar]
  112. 112.
    Siddiqi S, Saleem U, Abumrad NA, Davidson NO, Storch J, et al. 2010.. A novel multiprotein complex is required to generate the prechylomicron transport vesicle from intestinal ER. . J. Lipid Res. 51::191828
    [Crossref] [Google Scholar]
  113. 113.
    Siddiqi S, Zhelyabovska O, Siddiqi SA. 2018.. Reticulon 3 regulates very low density lipoprotein secretion by controlling very low density lipoprotein transport vesicle biogenesis. . Can. J. Physiol. Pharmacol. 96::66875
    [Crossref] [Google Scholar]
  114. 114.
    Siddiqi SA. 2008.. VLDL exits from the endoplasmic reticulum in a specialized vesicle, the VLDL transport vesicle, in rat primary hepatocytes. . Biochem. J. 413::33342
    [Crossref] [Google Scholar]
  115. 115.
    Siddiqi SA, Mansbach CM. 2008.. PKCζ-mediated phosphorylation controls budding of the pre-chylomicron transport vesicle. . J. Cell Sci. 121::232738
    [Crossref] [Google Scholar]
  116. 116.
    Stillemark-Billton P, Beck C, Borén J, Olofsson SO. 2005.. Relation of the size and intracellular sorting of apoB to the formation of VLDL 1 and VLDL 2. . J. Lipid Res. 46::10414
    [Crossref] [Google Scholar]
  117. 117.
    Strong A, Ding Q, Edmondson AC, Millar JS, Sachs KV, et al. 2012.. Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. . J. Clin. Investig. 122::280716
    [Crossref] [Google Scholar]
  118. 118.
    Sudhof TC, Rothman JE. 2009.. Membrane fusion: grappling with SNARE and SM proteins. . Science 323::47477
    [Crossref] [Google Scholar]
  119. 119.
    Taskinen MR, Packard CJ, Borén J. 2019.. Dietary fructose and the metabolic syndrome. . Nutrients 11::1987
    [Crossref] [Google Scholar]
  120. 120.
    Taskinen MR, Bjornson E, Kahri J, Soderlund S, Matikainen N, et al. 2021.. Effects of evolocumab on the postprandial kinetics of apo (apolipoprotein) B100- and B48-containing lipoproteins in subjects with type 2 diabetes. . Arterioscler. Thromb. Vasc. Biol. 41::96275
    [Crossref] [Google Scholar]
  121. 121.
    Taskinen MR, Bjornson E, Matikainen N, Soderlund S, Pietilainen KH, et al. 2021.. Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes. . Diabetes Obes. Metab. 23::1191201
    [Crossref] [Google Scholar]
  122. 122.
    Taskinen MR, Bjornson E, Matikainen N, Soderlund S, Ramo J, et al. 2022.. Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations. . JCI Insight 7::e160607
    [Crossref] [Google Scholar]
  123. 123.
    Taskinen MR, Matikainen N, Bjornson E, Soderlund S, Inkeri J, et al. 2023.. Contribution of intestinal triglyceride-rich lipoproteins to residual atherosclerotic cardiovascular disease risk in individuals with type 2 diabetes on statin therapy. . Diabetologia 66::230719
    [Crossref] [Google Scholar]
  124. 124.
    Thierer JH, Foresti O, Yadav PK, Wilson MH, Moll T, et al. 2022.. Pla2g12b is essential for expansion of nascent lipoprotein particles. . bioRxiv 2022.08.02.502564. https://doi.org/10.1101/2022.08.02.502564
  125. 125.
    Tiwari S, Siddiqi S, Siddiqi SA. 2013.. CideB protein is required for the biogenesis of very low density lipoprotein (VLDL) transport vesicle. . J. Biol. Chem. 288::515765
    [Crossref] [Google Scholar]
  126. 126.
    Tiwari S, Siddiqi S, Zhelyabovska O, Siddiqi SA. 2016.. Silencing of small valosin-containing protein-interacting protein (SVIP) reduces very low density lipoprotein (VLDL) secretion from rat hepatocytes by disrupting its endoplasmic reticulum (ER)-to-Golgi trafficking. . J. Biol. Chem. 291::1251426
    [Crossref] [Google Scholar]
  127. 127.
    Tiwari S, Siddiqi SA. 2012.. Intracellular trafficking and secretion of VLDL. . Arterioscler. Thromb. Vasc. Biol. 32::107986
    [Crossref] [Google Scholar]
  128. 128.
    van Zwol W, Rimbert A, Wolters JC, Smit M, Bloks VW, et al. 2022.. Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion. . Hepatology 78::141832
    [Google Scholar]
  129. 129.
    Verges B. 2022.. Intestinal lipid absorption and transport in type 2 diabetes. . Diabetologia 65::1587600
    [Crossref] [Google Scholar]
  130. 130.
    Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, et al. 2021.. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies with the special contribution of the European Association of Preventive Cardiology (EAPC). . Eur. Heart J. 42::3227337. . 2022.. Eur. Heart J. 43::4468
    [Google Scholar]
  131. 131.
    Wang H, Gilham D, Lehner R. 2007.. Proteomic and lipid characterization of apolipoprotein B-free luminal lipid droplets from mouse liver microsomes: implications for very low density lipoprotein assembly. . J. Biol. Chem. 282::3321826
    [Crossref] [Google Scholar]
  132. 132.
    Wang X, Wang H, Xu B, Huang D, Nie C, et al. 2021.. Receptor-mediated ER export of lipoproteins controls lipid homeostasis in mice and humans. . Cell Metab. 33::35066.e7
    [Crossref] [Google Scholar]
  133. 133.
    Wen Y, Chen YQ, Konrad RJ. 2022.. The regulation of triacylglycerol metabolism and lipoprotein lipase activity. . Adv. Biol. 6::e2200093
    [Crossref] [Google Scholar]
  134. 134.
    Wiggins D, Gibbons GF. 1992.. The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas. . Biochem. J. 284:(Part 2):45762
    [Crossref] [Google Scholar]
  135. 135.
    Wilkinson J, Higgins JA, Groot P, Gherardi E, Bowyer D. 1992.. Membrane-bound apolipoprotein B is exposed at the cytosolic surface of liver microsomes. . FEBS Lett. 304::2426
    [Crossref] [Google Scholar]
  136. 136.
    Wolfrum C, Asilmaz E, Luca E, Friedman JM, Stoffel M. 2004.. Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. . Nature 432::102732
    [Crossref] [Google Scholar]
  137. 137.
    Wolfrum C, Besser D, Luca E, Stoffel M. 2003.. Insulin regulates the activity of forkhead transcription factor Hnf-3β/Foxa-2 by Akt-mediated phosphorylation and nuclear/cytosolic localization. . PNAS 100::1162429
    [Crossref] [Google Scholar]
  138. 138.
    Wolska A, Reimund M, Sviridov DO, Amar MJ, Remaley AT. 2021.. Apolipoprotein mimetic peptides: potential new therapies for cardiovascular diseases. . Cells 10::597
    [Crossref] [Google Scholar]
  139. 139.
    Wong DM, Webb JP, Malinowski PM, Macri J, Adeli K. 2009.. Proteomic profiling of the prechylomicron transport vesicle involved in the assembly and secretion of apoB-48-containing chylomicrons in the intestinal enterocytes. . Proteomics 9::3698711
    [Crossref] [Google Scholar]
  140. 140.
    Wu JX, He KY, Zhang ZZ, Qu YL, Su XB, et al. 2021.. LZP is required for hepatic triacylglycerol transportation through maintaining apolipoprotein B stability. . PLOS Genet. 17::e1009357
    [Crossref] [Google Scholar]
  141. 141.
    Xiao C, Stahel P, Carreiro AL, Hung YH, Dash S, et al. 2019.. Oral glucose mobilizes triglyceride stores from the human intestine. . Cell. Mol. Gastroenterol. Hepatol. 7::31337
    [Crossref] [Google Scholar]
  142. 142.
    Xiao C, Stahel P, Lewis GF. 2019.. Regulation of chylomicron secretion: focus on post-assembly mechanisms. . Cell. Mol. Gastroenterol. Hepatol. 7::487501
    [Crossref] [Google Scholar]
  143. 143.
    Yao Z, Zhou H, Figeys D, Wang Y, Sundaram M. 2013.. Microsome-associated lumenal lipid droplets in the regulation of lipoprotein secretion. . Curr. Opin. Lipidol. 24::16070
    [Crossref] [Google Scholar]
  144. 144.
    Yin Y, Garcia MR, Novak AJ, Saunders AM, Ank RS, et al. 2018.. Surf4 (Erv29p) binds amino-terminal tripeptide motifs of soluble cargo proteins with different affinities, enabling prioritization of their exit from the endoplasmic reticulum. . PLOS Biol. 16::e2005140
    [Crossref] [Google Scholar]
  145. 145.
    Ying Q, Chan DC, Watts GF. 2021.. New insights into the regulation of lipoprotein metabolism by PCSK9: lessons from stable isotope tracer studies in human subjects. . Front. Physiol. 12::603910
    [Crossref] [Google Scholar]
  146. 146.
    Zadoorian A, Du X, Yang H. 2023.. Lipid droplet biogenesis and functions in health and disease. . Nat. Rev. Endocrinol. 19::44359
    [Crossref] [Google Scholar]
  147. 147.
    Zhou M, Fisher EA, Ginsberg HN. 1998.. Regulated co-translational ubiquitination of apolipoprotein B100. A new paradigm for proteasomal degradation of a secretory protein. . J. Biol. Chem. 273::2464953
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-nutr-062222-020716
Loading
/content/journals/10.1146/annurev-nutr-062222-020716
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error