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Biochemistry, Very Low Density Lipoprotein
Introduction
Very low-density lipoproteins (VLDL), along with chylomicrons, low-density lipoproteins (LDL), intermediate-density lipoproteins (IDL), and high-density lipoproteins (HDL) are the 5 major types of lipoproteins. These lipoproteins transport hydrophobic lipids such as phospholipids, triglycerides, and cholesterol in the plasma and extracellular fluids. Lipids, proteins, carbohydrates, and nucleic acids are the main components of cellular life. Lipids are vital for synthesizing cell membranes, energy storage, intracellular messaging, and transporting other essential organic substances such as vitamins. Lipoproteins allow for the transport of hydrophobic lipids in the hydrophilic environment of the body’s systemic circulation.[1]
The synthesis and secretion of VLDL into circulation by the liver is a highly complex and regulated process that plays a fundamental role in the overall homeostasis of lipids in the body. Recent evidence has shown that the enhanced production and secretion of VLDL or alterations in its regulatory system directly contribute to developing multiorgan diseases such as atherosclerosis.[2][3][4] There is an ongoing research effort to understand better the basic and complicated mechanisms behind the regulation and signaling of VLDL biogenesis to develop effective targeted therapies in the future.
Fundamentals
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Fundamentals
The composition of VLDL consists of approximately 90% lipids and 10% proteins. This proportion gives VLDL a low density of 0.96 to 1.006 g/ml, hence its name. Of its total lipid component, triglycerides take up to 70% of VLDL’s mass, with cholesterol esters and fatty acids making up the rest.[5] Regarding its lower protein component, VLDL is associated with multiple apolipoproteins: Apo B-100, Apo C-I, Apo C-II, Apo C-III, and Apo E.[6] Apolipoproteins are cofactors for numerous enzymes throughout the body, ligands for surface receptors, and essential structural elements. The biological functions and metabolism of VLDL are strongly related to these apolipoproteins, as well as VLDL’s potential role in disease development.[6]
Molecular Level
The lipid transport pathway starts in the small intestine when the dietary lipids (mainly triglycerides) are packaged into chylomicrons utilizing Apo B-48 as its backbone structure. Chylomicrons are then secreted into the lymphatic system to later travel throughout the systemic circulation. As they travel throughout the body, chylomicrons obtain Apo C-II and Apo-E from circulating HDL. The recently acquired Apo C-II acts as an activating cofactor for lipoprotein lipase (LPL), which hydrolyzes the triglycerides found in the chylomicrons’ core and allows it to release free fatty acids to the peripheral tissues. As chylomicrons lose their triglycerides by the action of peripheral LPL, they transform into chylomicron remnants. These remnants use their Apo-E as high-affinity ligands to bind to hepatic receptors and internalize into the liver.[1]
In the hepatocytes, triglycerides and cholesterol esters are transferred to Apo B-100 by the action of the microsomal triglyceride transfer protein (MTTP). This lipidated Apo B-100 is now called nascent VLDL and is secreted to the circulation.[7][8] Like chylomicrons, Nascent VLDL obtains Apo C-II and Apo-E from circulating HDL and is now termed mature VLDL. Mature VLDL transports endogenous lipids from the liver to the peripheral adipose, cardiac, and muscle tissues (unlike chylomicrons, which carry exogenous dietary lipids from the small intestine).[9]
The Apo C-II in mature VLDL activates LPL in the capillary endothelium of tissues to cleave their stored triglycerides into 1 monoglyceride and 2 free fatty acids, releasing them from the VLDL and allowing them to be delivered to the tissues to be used for storage or energy production.[9][10] Insulin also upregulates Apo C-II's activity and increases triglyceride hydrolysis into free fatty acids for tissue absorption. Simultaneously, the cholesterol ester transfer protein (CETP) promotes the exchange of VLDL’s triglycerides and phospholipids for HDL’s cholesterol esters. After releasing enough triglycerides either into the tissues or to HDL, the core of the VLDL gets reduced, and the VLDL remnant is now called IDL. Approximately half of the circulating IDL is then taken by the liver by binding to the Apo B-100 and Apo-E. The remaining half of the IDL loses its Apo-E and transforms into LDL through the action of the hepatic lipase.
The alteration or deficiency of the enzymes involved in this complex metabolic process may lead to lipid disorders known as hyperlipoproteinemia. These diseases are divided into 5 subtypes depending on the pathophysiology and clinical presentation. Type I hyperlipoproteinemia (familial hyperchylomicronemia) is caused by a deficiency in LPL or Apo C-II, significantly increasing triglyceride concentration. These patients present with eruptive xanthomas, steatosis, recurrent episodes of acute pancreatitis, and no increased risk of atherosclerosis.[11] Defective or deficient LDL receptors or Apo B-100 causes type II hyperlipoproteinemia (familial hypercholesterolemia). This causes an important elevation in LDL (usually >600 mg/dl in homozygotes or >250 mg/dl in heterozygotes) and VLDL cholesterol. These patients present with tuberous xanthomas, xanthelasmas, and premature atherosclerosis, which may lead to acute coronary syndromes in young patients (<20 years of age).[12] Type III hyperlipoproteinemia (familial dysbetalipoproteinemia) is caused by an alteration in Apo-E, which increases VLDL and chylomicrons, leading to premature atherosclerosis.[13] Type IV hyperlipoproteinemia (familial hypertriglyceridemia) is caused by hepatic overproduction of VLDL, leading to a massive increase in triglyceride concentrations (usually >1000 mg/dl), causing premature atherosclerosis and recurrent episodes of acute pancreatitis (similar to type I).[14][15] Finally, type V (mixed hyperlipidemia) is caused by a sporadic defect in Apo A5 and presents with xanthomas, abdominal pain, and clinical features of hyperglycemia.[16][17]
Function
LDL plays a key role in forming atherosclerotic plaques that lead to atherosclerotic cardiovascular disease. Directly measuring LDL and VLDL by ultracentrifugation is extremely expensive and time-consuming. For this reason, multiple time and money-saving equations have been developed to estimate the LDL and VLDL cholesterol levels. Most famously known, the Friedewald equation subtracts HDL and VLDL from the total cholesterol level to estimate LDL concentration. In turn, VLDL levels are estimated by a fixed ratio of triglycerides/5.[18]
Initially intended for research purposes only, this equation has been widely utilized over the last decades to estimate LDL cholesterol levels clinically.[19] This equation, however, is not without its limitations and inaccuracies. This measurement becomes unreliable at high triglyceride (>400 mg/dl) and low LDL concentrations. With the increased prevalence of obesity, metabolic syndrome, and diabetes, higher triglyceride levels are increasingly common, and special consideration needs to be taken when indirectly estimating both LDL and VLDL.[20]
Pathophysiology
Diet, sex, and race are factors that significantly influence VLDL production and secretion. VLDL synthesis is mainly related to lipid intake, with secretion increasing in the postprandial state. High-fat diets have been associated with higher VLDL secretion, usually presenting as increased blood triglyceride levels.[21][22] Studies have inconsistently reported the timing of postprandial VLDL peaks, ranging from 30 minutes up to 5 or 6 hours. Nonetheless, multiple studies have found that insulin resistance, metabolic syndrome, and obesity are strongly associated with longer plateaus and higher peaks of VLDL levels.[23][24] Women have also been shown to have lower VLDL concentrations than men, although the cause of this sex difference is not completely understood.[25] VLDL has been associated with the development of multiple pathological conditions involving the cardiovascular, endocrine, renal, hepatic, and nervous systems, as well as cancer and several autoimmune and dermatological diseases.
Clinical Significance
The impact of VLDL on cardiovascular diseases is mainly correlated to its role in atherosclerosis and coronary disease.[26] The accumulation of triglyceride-predominant lipoproteins such as chylomicrons and VLDL strongly contributes to the rupture of atherosclerotic plaques. Additionally, VLDL has been associated with peripheral artery disease, leading to occlusive limb events, vascular stiffness, and carotid artery thickness.[27] Besides the lipidic components of VLDL, its apolipoprotein composition also directly affects the development of cardiovascular disorders. Studies have shown that higher Apo-B and lower Apo C-III concentrations are associated with higher cardiovascular risk.[28][29] This leads to the hypothesis that Apo-B is one of the major drivers in the development of atherosclerosis.[30]
Beyond its direct relation with atherosclerosis, VLDL also plays an important role in metabolic syndrome and insulin resistance. In a normal physiologic state, insulin suppresses the production and secretion of VLDL. In subjects with insulin resistance, an enhanced synthesis and reduced clearance of VLDL is often detected as increased plasma triglyceride levels.[31][32] In these subjects with insulin resistance, there is also a dysfunction in lipid storage in adipose tissue, making them prone to hyperlipidemia. Further, VLDL in metabolic syndrome can induce macrophage apoptosis by increasing reactive oxygen species production. These cytotoxic properties cause VLDL to be highly pro-inflammatory and atherogenic.[29]
VLDL cholesterol is also associated with hepatic disorders such as non-alcoholic fatty liver disease (NAFLD) and hepatitis. Liver fat content has been previously associated with other features of chronic insulin resistance, such as glucose intolerance, increased insulin levels, and intra-abdominal fat.[2] In subjects with NAFLD, there is increased hydrolysis of intrahepatic triglycerides, leading to increased secretion of VLDL. Patients with NAFLD also have an altered synthesis, oxidation, and reduction of VLDL particles due to the impaired effects of insulin.[31] It has been theorized that the lessened effects of insulin lead to an increase in lipid deposition from adipose tissue to the liver. Elevations in blood glucose can further increase fat accumulation in the liver, resulting in enhanced production of VLDL and leading to the expected hyperlipidemia associated with diabetes.[2]
Various hormones also affect VLDL levels, with their metabolism closely related to several endocrinological mechanisms. In Cushing syndrome, the increased concentration of cortisol increases the plasma levels of both VLDL and LDL cholesterol by reducing the degradation of Apo B and increasing the rate of adipose tissue lipolysis.[33] This results in expected dyslipidemia and increased cardiovascular risk associated with Cushing syndrome. VLDL stimulates aldosterone production and potentially leads to hypertension. This also explains how statins are associated with a decrease in aldosterone concentrations.[34] Growth hormone also has a direct effect on VLDL metabolism.[35] Growth hormone deficiency is associated with increased VLDL synthesis and decreased clearance. This mechanism explains the association between hypopituitarism and a higher cardiovascular and cerebrovascular risk. Moreover, thyroid hormones affect the activity of LPL and strongly relate to cholesterol metabolism. The deficiency of thyroid hormones in hypothyroidism leads to reduced LPL function and increased hepatic VLDL production associated with hyperlipidemia and higher cardiovascular risk.[36] VLDL has also been implicated in developing neurocognitive dysfunction, chronic kidney disease, and cancer.[37][38][39]
In conclusion, VLDL cholesterol is synthesized in the liver to transport endogenous lipids such as triglycerides and cholesterol esters to the peripheral (mainly adipose, skeletal, and cardiac) tissues. It has been strongly associated with developing several multiorgan diseases such as atherosclerosis, coronary artery disease, non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome, neurocognitive impairment, autoimmune disease, dermatological disorders, and cancer. It is crucial to study and understand the mechanisms behind VLDL’s biosynthesis, regulation, signaling, and secretion to comprehend its contribution to human health and to potentially develop targeted therapies that may lead directly to better patient care.
References
Lent-Schochet D, Jialal I. Biochemistry, Lipoprotein Metabolism. StatPearls. 2024 Jan:(): [PubMed PMID: 31985986]
Adiels M, Taskinen MR, Packard C, Caslake MJ, Soro-Paavonen A, Westerbacka J, Vehkavaara S, Häkkinen A, Olofsson SO, Yki-Järvinen H, Borén J. Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia. 2006 Apr:49(4):755-65 [PubMed PMID: 16463046]
Johansen MØ, Nielsen SF, Afzal S, Vedel-Krogh S, Davey Smith G, Nordestgaard BG. Very Low-Density Lipoprotein Cholesterol May Mediate a Substantial Component of the Effect of Obesity on Myocardial Infarction Risk: The Copenhagen General Population Study. Clinical chemistry. 2021 Jan 8:67(1):276-287. doi: 10.1093/clinchem/hvaa290. Epub [PubMed PMID: 33409531]
Balling M,Afzal S,Varbo A,Langsted A,Davey Smith G,Nordestgaard BG, VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins. Journal of the American College of Cardiology. 2020 Dec 8; [PubMed PMID: 33272366]
Dashti M, Kulik W, Hoek F, Veerman EC, Peppelenbosch MP, Rezaee F. A phospholipidomic analysis of all defined human plasma lipoproteins. Scientific reports. 2011:1():139. doi: 10.1038/srep00139. Epub 2011 Nov 7 [PubMed PMID: 22355656]
Dashty M, Motazacker MM, Levels J, de Vries M, Mahmoudi M, Peppelenbosch MP, Rezaee F. Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism. Thrombosis and haemostasis. 2014 Mar 3:111(3):518-30. doi: 10.1160/TH13-02-0178. Epub 2014 Feb 6 [PubMed PMID: 24500811]
Gibbons GF, Wiggins D, Brown AM, Hebbachi AM. Synthesis and function of hepatic very-low-density lipoprotein. Biochemical Society transactions. 2004 Feb:32(Pt 1):59-64 [PubMed PMID: 14748713]
Level 3 (low-level) evidenceTiwari S,Siddiqi SA, Intracellular trafficking and secretion of VLDL. Arteriosclerosis, thrombosis, and vascular biology. 2012 May; [PubMed PMID: 22517366]
Level 3 (low-level) evidenceNimpf J, Schneider WJ. From cholesterol transport to signal transduction: low density lipoprotein receptor, very low density lipoprotein receptor, and apolipoprotein E receptor-2. Biochimica et biophysica acta. 2000 Dec 15:1529(1-3):287-98 [PubMed PMID: 11111096]
Level 3 (low-level) evidenceShelness GS, Sellers JA. Very-low-density lipoprotein assembly and secretion. Current opinion in lipidology. 2001 Apr:12(2):151-7 [PubMed PMID: 11264986]
Level 3 (low-level) evidenceTeramoto R, Tada H, Kawashiri MA, Nohara A, Nakahashi T, Konno T, Inazu A, Mabuchi H, Yamagishi M, Hayashi K. Molecular and functional characterization of familial chylomicronemia syndrome. Atherosclerosis. 2018 Feb:269():272-278. doi: 10.1016/j.atherosclerosis.2017.11.006. Epub 2017 Nov 14 [PubMed PMID: 29153744]
Abifadel M,Boileau C, Genetic and molecular architecture of familial hypercholesterolemia. Journal of internal medicine. 2022 Oct 4; [PubMed PMID: 36196022]
Sampson M, Wolska A, Meeusen JW, Donato LJ, Jaffe AS, Remaley AT. Identification of Dysbetalipoproteinemia by an Enhanced Sampson-NIH Equation for Very Low-Density Lipoprotein-Cholesterol. Frontiers in genetics. 2022:13():935257. doi: 10.3389/fgene.2022.935257. Epub 2022 Jul 14 [PubMed PMID: 35910208]
Rodrigues KF, Yong WTL, Bhuiyan MSA, Siddiquee S, Shah MD, Venmathi Maran BA. Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review. Biology. 2022 Sep 2:11(9):. doi: 10.3390/biology11091308. Epub 2022 Sep 2 [PubMed PMID: 36138787]
Level 3 (low-level) evidenceGrundy SM. Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome. The American journal of cardiology. 1998 Feb 26:81(4A):18B-25B [PubMed PMID: 9526809]
Level 3 (low-level) evidenceWang J,Ban MR,Kennedy BA,Anand S,Yusuf S,Huff MW,Pollex RL,Hegele RA, APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia. Nature clinical practice. Cardiovascular medicine. 2008 Nov; [PubMed PMID: 18779834]
Level 2 (mid-level) evidenceFallat RW, Glueck CJ. Familial and acquired type V hyperlipoproteinemia. Atherosclerosis. 1976 Jan-Feb:23(1):41-62 [PubMed PMID: 1078394]
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 1972 Jun:18(6):499-502 [PubMed PMID: 4337382]
Warnick GR, Knopp RH, Fitzpatrick V, Branson L. Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clinical chemistry. 1990 Jan:36(1):15-9 [PubMed PMID: 2297909]
Martin SS, Blaha MJ, Elshazly MB, Brinton EA, Toth PP, McEvoy JW, Joshi PH, Kulkarni KR, Mize PD, Kwiterovich PO, Defilippis AP, Blumenthal RS, Jones SR. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. Journal of the American College of Cardiology. 2013 Aug 20:62(8):732-9. doi: 10.1016/j.jacc.2013.01.079. Epub 2013 Mar 21 [PubMed PMID: 23524048]
Lambert JE, Parks EJ. Postprandial metabolism of meal triglyceride in humans. Biochimica et biophysica acta. 2012 May:1821(5):721-6. doi: 10.1016/j.bbalip.2012.01.006. Epub 2012 Jan 17 [PubMed PMID: 22281699]
Nakajima K, Nakano T, Tokita Y, Nagamine T, Inazu A, Kobayashi J, Mabuchi H, Stanhope KL, Havel PJ, Okazaki M, Ai M, Tanaka A. Postprandial lipoprotein metabolism: VLDL vs chylomicrons. Clinica chimica acta; international journal of clinical chemistry. 2011 Jul 15:412(15-16):1306-18. doi: 10.1016/j.cca.2011.04.018. Epub 2011 Apr 19 [PubMed PMID: 21531214]
Level 3 (low-level) evidenceSøndergaard E, Johansen RF, Jensen MD, Nielsen S. Postprandial VLDL-TG metabolism in type 2 diabetes. Metabolism: clinical and experimental. 2017 Oct:75():25-35. doi: 10.1016/j.metabol.2017.07.002. Epub 2017 Jul 19 [PubMed PMID: 28964326]
Lee HC, Shin SJ, Huang JK, Lin MY, Lin YH, Ke LY, Jiang HJ, Tsai WC, Chao MF, Lin YH. The role of postprandial very-low-density lipoprotein in the development of atrial remodeling in metabolic syndrome. Lipids in health and disease. 2020 Sep 22:19(1):210. doi: 10.1186/s12944-020-01386-5. Epub 2020 Sep 22 [PubMed PMID: 32962696]
Gormsen LC, Høst C, Hjerrild BE, Gravholt CH, Nielsen S. Acute estrogen exposure does not affect basal very low-density lipoprotein-triglyceride production or oxidation in postmenopausal women. European journal of endocrinology. 2010 Sep:163(3):421-6. doi: 10.1530/EJE-10-0551. Epub 2010 Jun 21 [PubMed PMID: 20566588]
Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ, Pfeffer MA, Braunwald E. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 2000 Oct 17:102(16):1886-92 [PubMed PMID: 11034934]
Level 2 (mid-level) evidenceGentile M,Iannuzzi A,Giallauria F,D'Andrea A,Venturini E,Pacileo M,Covetti G,Panico C,Mattiello A,Vitale G,Sarullo FM,Rubba P,Vigorito C,Panico S,Iannuzzo G, Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels. Journal of clinical medicine. 2020 May 11; [PubMed PMID: 32403373]
Ginsberg HN, Packard CJ, Chapman MJ, Borén J, Aguilar-Salinas CA, Averna M, Ference BA, Gaudet D, Hegele RA, Kersten S, Lewis GF, Lichtenstein AH, Moulin P, Nordestgaard BG, Remaley AT, Staels B, Stroes ESG, Taskinen MR, Tokgözoğlu LS, Tybjaerg-Hansen A, Stock JK, Catapano AL. 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. European heart journal. 2021 Dec 14:42(47):4791-4806. doi: 10.1093/eurheartj/ehab551. Epub [PubMed PMID: 34472586]
Level 3 (low-level) evidenceMendivil CO, Rimm EB, Furtado J, Sacks FM. Apolipoprotein E in VLDL and LDL with apolipoprotein C-III is associated with a lower risk of coronary heart disease. Journal of the American Heart Association. 2013 May 14:2(3):e000130. doi: 10.1161/JAHA.113.000130. Epub 2013 May 14 [PubMed PMID: 23672999]
Marston NA, Giugliano RP, Melloni GEM, Park JG, Morrill V, Blazing MA, Ference B, Stein E, Stroes ES, Braunwald E, Ellinor PT, Lubitz SA, Ruff CT, Sabatine MS. Association of Apolipoprotein B-Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis: Distinguishing Between Particle Concentration, Type, and Content. JAMA cardiology. 2022 Mar 1:7(3):250-256. doi: 10.1001/jamacardio.2021.5083. Epub [PubMed PMID: 34773460]
Poulsen MK, Nellemann B, Stødkilde-Jørgensen H, Pedersen SB, Grønbæk H, Nielsen S. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Nonalcoholic Fatty Liver Disease. The Journal of clinical endocrinology and metabolism. 2016 Apr:101(4):1637-46. doi: 10.1210/jc.2015-3476. Epub 2016 Feb 1 [PubMed PMID: 26829441]
Tricò D, Natali A, Mari A, Ferrannini E, Santoro N, Caprio S. Triglyceride-rich very low-density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents. Diabetes, obesity & metabolism. 2018 Dec:20(12):2905-2910. doi: 10.1111/dom.13467. Epub 2018 Aug 2 [PubMed PMID: 30003666]
Giordano R, Picu A, Marinazzo E, D'Angelo V, Berardelli R, Karamouzis I, Forno D, Zinnà D, Maccario M, Ghigo E, Arvat E. Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission. Clinical endocrinology. 2011 Sep:75(3):354-60. doi: 10.1111/j.1365-2265.2011.04055.x. Epub [PubMed PMID: 21521323]
Baudrand R, Pojoga LH, Vaidya A, Garza AE, Vöhringer PA, Jeunemaitre X, Hopkins PN, Yao TM, Williams J, Adler GK, Williams GH. Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects. Circulation. 2015 Nov 10:132(19):1825-33. doi: 10.1161/CIRCULATIONAHA.115.016759. Epub 2015 Oct 2 [PubMed PMID: 26432671]
Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocrine reviews. 2009 Apr:30(2):152-77. doi: 10.1210/er.2008-0027. Epub 2009 Feb 24 [PubMed PMID: 19240267]
Fabbrini E,Magkos F,Patterson BW,Mittendorfer B,Klein S, Subclinical hypothyroidism and hyperthyroidism have opposite effects on hepatic very-low-density lipoprotein-triglyceride kinetics. The Journal of clinical endocrinology and metabolism. 2012 Mar; [PubMed PMID: 22238397]
Yogi-Morren D, Galioto R, Strandjord SE, Kennedy L, Manroa P, Kirwan JP, Kashyap S, Gunstad J. Duration of type 2 diabetes and very low density lipoprotein levels are associated with cognitive dysfunction in metabolic syndrome. Cardiovascular psychiatry and neurology. 2014:2014():656341. doi: 10.1155/2014/656341. Epub 2014 Jun 25 [PubMed PMID: 25057411]
Miljkovic M, Stefanovic A, Simic-Ogrizovic S, Vekic J, Bogavac-Stanojevic N, Cerne D, Kocbek P, Marc J, Jelic-Ivanovic Z, Spasojevic-Kalimanovska V, Kotur-Stevuljevic J. Association of Dyslipidemia, Oxidative Stress, and Inflammation With Redox Status in VLDL, LDL, and HDL Lipoproteins in Patients With Renal Disease. Angiology. 2018 Nov:69(10):861-870. doi: 10.1177/0003319718780041. Epub 2018 Jun 18 [PubMed PMID: 29909653]
Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Advanced drug delivery reviews. 2020:159():245-293. doi: 10.1016/j.addr.2020.07.013. Epub 2020 Jul 23 [PubMed PMID: 32711004]