DOCSLIB.ORG

Apolipoproteins and Their Association with Cardiometabolic Risk

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Apolipoproteins and Their Association with Cardiometabolic Risk Nutr Hosp. 2015;32(6):2674-2683 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Original / Síndrome metabólico Apolipoproteins and their association with cardiometabolic risk biomarkers in adolescents Mellina Neyla de Lima Albuquerque1, Alcides da Silva Diniz1 and Ilma Kruze Grande de Arruda1 1Department of Nutrition. Federal University of Pernambuco, Recife, Brazil. Abstract APOLIPOPROTEÍNAS Y SU ASOCIACIÓN CON BIOMARCADORES DE RIESGO Introduction: the apoB/apo A-I ratio has been reported CARDIOMETABÓLICO EN ADOLESCENTES as an important predictor of cardiovascular risk, being superior to lipids, lipoproteins and conventional lipid ra- tios. Resumen Objective: to investigate the association between apo- Introducción: la razón apo B/apo A-I sigue siendo lipoproteins A-I and B, and the apolipoprotein B/apoli- reportada como un predictor importante de riesgo car- poprotein A-I ratio and cardiometabolic risk variables in diovascular, superior a lípidos, lipoproteínas y razones adolescents. lipídicas convencionales. Objetivo: investigar la asocia- Methods: this was a cross-sectional study including ción entre las apolipoproteínas A-I y B y la razón apoli- 104 adolescents of public schools in Recife during the poproteína B/apolipoproteína A-I con variables de riesgo months of March/April, 2013. Sociodemographic, an- cardiometabólico en adolescentes. thropometric, clinical and biochemical variables were Métodos: estudio de corte transversal que incluye a analysed. The apolipoproteins were analysed via Immu- 104 adolescentes de escuelas públicas de Recife, entre noturbidimetry. marzo/abril de 2013. Se evaluaron variables clínicas, Results: body mass index, waist circumference, waist bioquímicas, antropométricas y sociodemográficas. Se circumference/height, triglycerides, cholesterol/HDL, analizaron las apolipoproteínas por imunoturbidimetría. and apolipoprotein B/apolipoprotein A-I declined with Resultados: índice de masa corporal, circunferencia de the progress of the percentile distribution of apolipo- la cintura, circunferencia de la cintura/altura, triglicéri- protein A-I concentrations, while the HDL and apoli- dos, colesterol/HDL y apolipoproteína B/apolipoproteí- poprotein B increased between the first and last quartiles na A-I mostraron una reducción con la progresión de la of the apolipoprotein A-I concentrations. Systolic blood distribución en percentil de las concentraciones de apo- pressure, body mass index, waist circumference, waist lipoproteína A-I, mientras que HDL y apolipoproteína B circumference/height, cholesterol, LDL, triglycerides, aumentaron entre el primero y el último cuartil de las cholesterol/HDL, and LDL/HDL increased progressively concentraciones de apolipoproteína A-I. Tensión arterial in the quartile distribution of the concentrations of apo- sistólica, índice de masa corporal, circunferencia de la lipoprotein B and apolipoprotein B/apolipoprotein A-I. cintura, circunferencia de la cintura/altura, colesterol, Alfa-1-acid glycoprotein serum levels increased hand-in- LDL, triglicéridos, colesterol/HDL y LDL/HDL presenta- hand with the percentile progression of apolipoprotein B. ron un aumento progresivo en la distribución en cuartiles Conclusions: the findings underline an important de las concentraciones de apolipoproteína B y de la apoli- asso ciation of apolipoproteins A-I and B, and the apoli- poproteína B/apolipoproteína A-I. Los niveles séricos de poprotein B/apolipoprotein A-I ratio and their clinical, alfa-1-glicoproteína ácida aumentaron paralelamente a biochemical and anthropometric cardiometabolic risk. la progresión en percentil de apolipoproteína B. However, prospective studies are important to evaluate Conclusiones: los hallazgos evidencian una asociación the pertinence of implementing these markers in the cli- importante de las apolipoproteínas A-I y B y de la razón nical practice. apolipoproteína B/apolipoproteína A-I con biomarcado- (Nutr Hosp. 2015;32:2674-2683) res clínicos, bioquímicos y antropométricos de riesgo car- diometabólico. Sin embargo, son recomendables estudios DOI:10.3305/nh.2015.32.6.9779 prospectivos para evaluar la pertenencia de la implemen- Key words: Apolipoprotein A-I. Apolipoprotein B. Dysli- tación de esos marcadores en la práctica clínica. pidemias. Adolescent. (Nutr Hosp. 2015;32:2674-2683) DOI:10.3305/nh.2015.32.6.9779 Correspondence: Mellina Neyla de Lima Albuquerque. Palabras clave: Apolipoproteína A-I. Apolipoproteína B. o Av. Liberdade, 110, Ed. Bouganville, apt . 104, Dislipidemias. Adolescente. Sancho, 50920-310, Recife, PE, Brasil. E-mail: [email protected] Recibido: 17-VIII-2015. Aceptado: 9-IX-2015. 2674 042_9779 - Apolipoproteinas y su asociacion.indd 2674 9/12/15 4:13 Abbreviations cholesterol deposition, endothelial dysfunction and, as a result, higher risk of atherogenesis6,8. This is why the AGP: Alfa-1-acid glycoprotein. apoB/apo A-I ratio has been reported as an important APO A-I: Apolipoprotein A-I. predictor of cardiovascular risk, being superior to li- APO B: Apolipoprotein B. pids, lipoproteins and conventional lipid ratios, such BMI: Body mass index. as total cholesterol/HDL9. DBP: Diastolic blood pressure. Considering the magnitude of the coronary arterial HDL: High-density lipoprotein. disease at earlier ages, all over the world, this study LDL: Low-density lipoprotein. aimed at investigating the association of both apoli- SBP: Systolic blood pressure. poproteins A-I and B and the apoB/apoA-I ratio with TAG: Triglycerides. cardiometabolic risk variables in adolescents of public TC: Total cholesterol. schools in Recife, Northeast Brazil. WC: Waist circumference. Materials and methods Introduction Study Design and Population Although the atherosclerotic disease in general prevails in the adult age, cardiovascular risk markers The investigation derived from a larger project titled have been identified in children1 and adolescents2, “Dyslipidemia and its association with excessive wei- indicating their need to be investigated in these age ght, sedentary lifestyle and oxidative stress in a cohort ranges3. Regarding the lipid profile, it has been obser- of school students in Recife, PE”. An evaluation was ved that the risk of atherosclerotic disease seems to made of the anthropometric, lipid profile, food con- be more closely related to the number of circulating sumption and lifestyle parameters, in addition to so- atherogenic particles that contact and go through the cioeconomic and demographic aspects, in the baseline arterial wall, than with the isolated concentrations of of this project. cholesterol contained in those lipoprotein fractions4. The outline of the research comprised a cross-sec- Consequently, measuring blood concentrations of apo- tional study, nested in this cohort, the eligible popula- lipoproteins B and A-I has been considered for expres- tion of which consisted of adolescents of both genders sing more appropriately the balance of atherogenic and from 12 to 19 years of age, recruited in public schools antiatherogenic particles5. of Recife, in the period from March to April 2013. Apolipoproteins are structural and functional pro- In order to size the sample, a pilot study was under- teins of the lipoprotein particles6, which perform im- taken, and a prevalence was found showing a 50.0% portant functions for the lipoprotein metabolism as increase in triglycerides (TAG) serum concentrations carriers of these hydrophobic molecules in the plasma between the first and the last quartile of the apoB/ aqueous medium, binding to the specific receptors on apoA-I index distribution. In defining the sample size, the cell surface to conduct the lipids correctly to the an equation was used to calculate the sample with infi- target organs and tissues of the organism. They also nite population10 [n = z2 x pq/d2], where z = confidence activate or inhibit the enzymes involved in the lipid interval (1.96), p = estimated prevalence (50.0%), and metabolism4,7. d = margin of error (14.0%). As this is a “finite” popu- Apolipoprotein A-I (apo A-I) is largest structural lation, the sample “n” was adjusted according to the protein component of the high-density lipoprotein equation [n = n/1 + (n/N)]11, where n = sample “n” (49), (HDL). It is responsible for stimulating the reverse and N = population size (409). Then, a correction was cholesterol transport, removing the exceeding choles- made due to the effect of the sample design (factor 2.1) terol from the tissues and redirecting it to the liver8, per cluster, resulting in a minimum number of sample and it may also be responsible for the anti-inflam- units of 92 individuals. In order to repair any losses, a matory and anti-oxidant properties of the HDL4. choice was made to correct the sample size by 10.0% Apolipoprotein B (apo B) accounts for approxima- [100/(100-10)], resulting in a final sample of 103 ado- tely 90% of the protein in the low-density lipoprotein lescents. (LDL), and it is the principal functional protein for ca- rrying cholesterol to the peripheral cells. It is present in kilomicrons (apo B-48), in the very low density and Evaluation Techniques and Methods intermediary lipoproteins, and in the LDL such as apo B-1007, correlating with the non-HDL cholesterol le- The researchers conducted the fieldwork supervi- vel1. sion, and a previously trained technical team collected The apoB/apoA-I ratio, therefore, reflects the cho- the data. The technical team is experienced in chec- lesterol balance of the potentially atherogenic and an- king clinical and anthropometrical measures,
Load more

Recommended publications
  • The Crucial Roles of Apolipoproteins E and C-III in Apob Lipoprotein Metabolism in Normolipidemia and Hypertriglyceridemia
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Harvard University - DASH The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Sacks, Frank M. 2015. “The Crucial Roles of Apolipoproteins E and C-III in apoB Lipoprotein Metabolism in Normolipidemia and Hypertriglyceridemia.” Current Opinion in Lipidology 26 (1) (February): 56–63. doi:10.1097/mol.0000000000000146. Published Version doi:10.1097/MOL.0000000000000146 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:30203554 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#OAP HHS Public Access Author manuscript Author Manuscript Author ManuscriptCurr Opin Author Manuscript Lipidol. Author Author Manuscript manuscript; available in PMC 2016 February 01. Published in final edited form as: Curr Opin Lipidol. 2015 February ; 26(1): 56–63. doi:10.1097/MOL.0000000000000146. The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia Frank M. Sacks Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Abstract Purpose of review—To describe the roles of apolipoprotein C-III (apoC-III) and apoE in VLDL and LDL metabolism Recent findings—ApoC-III can block clearance from the circulation of apolipoprotein B (apoB) lipoproteins, whereas apoE mediates their clearance.
    [Show full text]
  • Apolipoprotein B
    Laboratory Procedure Manual Analyte: Apolipoprotein B Matrix: Serum Method: Turbidimetric Assay on Roche Cobas® 6000 Method No.: Revised: As performed by: University of Minnesota – Advanced Research Diagnostics Laboratory (ARDL) Contact: Dr. Anthony Killeen, MD, PhD University of Minnesota Medical Center Fairview-University Medical Center University Campus Minneapolis, Minnesota Important Information for Users University of Minnesota – Advanced Research Diagnostics Laboratory (ARDL) periodically refines these laboratory methods. It is the responsibility of the user to contact the person listed on the title page of each write-up before using the analytical method to find out whether any changes have been made and what revisions, if any, have been incorporated. Apolipoprotein B NHANES 2015-2016 Public Release Data Set Information This document details the Lab Protocol for testing the items listed in the following table: Data File Name Variable Name SAS Label LBXAPB Apolipoprotein B (mg/dL) APOB_I LBDAPBSI Apolipoprotein B (g/L) 2 of 20 Apolipoprotein B NHANES 2015-2016 1. SUMMARY OF TEST PRINCIPLE AND CLINICAL RELEVANCE A. Clinical Relevance Apolipoproteins are the protein constituents of the lipoproteins. Apolipoprotein B (Apo B) is the major protein component of low-density lipoprotein (LDL). About one-third of the LDL particles provide cholesterol to peripheral cells. The other two-thirds are metabolized by the liver. LDL-uptake in all of these cells occurs via LDL receptors. Apo B levels increase in hypercholesterolemia, pregnancy, LDL receptor defects, bile obstruction and nephrotic syndrome. Apo B levels decrease in liver disease, sepsis and estrogen administration. The combined measurement of apolipoprotein A-1 (Apo A1, present in HDL) and Apo B and the calculation of the Apo B:Apo A1 ratio can reflect a lipid metabolism disorder and the risk of developing atherosclerosis or coronary heart disease.
    [Show full text]
  • Common Genetic Variations Involved in the Inter-Individual Variability Of
    nutrients Review Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence Mohammad M. H. Abdullah 1 , Itzel Vazquez-Vidal 2, David J. Baer 3, James D. House 4 , Peter J. H. Jones 5 and Charles Desmarchelier 6,* 1 Department of Food Science and Nutrition, Kuwait University, Kuwait City 10002, Kuwait; [email protected] 2 Richardson Centre for Functional Foods & Nutraceuticals, University of Manitoba, Winnipeg, MB R3T 6C5, Canada; [email protected] 3 United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA; [email protected] 4 Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; [email protected] 5 Nutritional Fundamentals for Health, Vaudreuil-Dorion, QC J7V 5V5, Canada; [email protected] 6 Aix Marseille University, INRAE, INSERM, C2VN, 13005 Marseille, France * Correspondence: [email protected] Abstract: The number of nutrigenetic studies dedicated to the identification of single nucleotide Citation: Abdullah, M.M.H.; polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has Vazquez-Vidal, I.; Baer, D.J.; House, increased considerably over the last decade. However, the robustness of the evidence-based sci- J.D.; Jones, P.J.H.; Desmarchelier, C. ence supporting the area remains to be evaluated. The objective of this review was to present Common Genetic Variations Involved recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol in the Inter-Individual Variability of metabolism and transport, and dietary intakes or interventions on circulating cholesterol concen- Circulating Cholesterol trations, which are causally involved in cardiovascular diseases and established biomarkers of Concentrations in Response to Diets: cardiovascular health.
    [Show full text]
  • Cholesterol and Saturated Fat Intake Determine the Effect Of
    article September 2006 ⅐ Vol. 8 ⅐ No. 9 Cholesterol and saturated fat intake determine the effect of polymorphisms at ABCG5/ABCG8 genes on lipid levels in children Enrique Viturro, PhD1, Manuel de Oya, PhD, MD1, Miguel A. Lasuncio´n, PhD2, Lydia Gorgojo, PhD, MD3, Jose´ M. Martı´n Moreno, PhD, MD3, Mercedes Benavente, PhD1, Beatriz Cano, PhD1, and Carmen Garces, PhD1 Purpose: Analysis of mutations in genes of the cholesterol metabolic pathway has not completely explained the interindividual variability of blood cholesterol concentrations attributed to gene–nutrient interactions. Thus, we analyzed polymorphisms in the ABCG5 and ABCG8 genes, involved in the regulation of intestinal cholesterol absorption, with special interest in a potential interaction with diet to determine lipid levels. Methods: The polymorphisms ABCG5 C1950G (Gln604Glu) and ABCG8 C1895T (Ala640Val) were determined by polymerase chain reaction and restriction analysis in 1227 healthy school children, aged 6 to 8 years. Results: No significant differences were found in blood lipid levels between subjects with different genotypes of the two analyzed polymorphisms. However, important differences appeared when separating subjects by their different lipid intake. The presence of the ABCG8 C1895T and ABCG5 C1950G polymorphisms was associated with different plasma total cholesterol, low-density lipoprotein cholesterol complex, and apolipoprotein B levels only in low-cholesterol consumers (significantly for the C1895T polymorphism), and among children within the lower tertile of saturated fat intake (significantly for the C1950G polymorphism). Conclusion: Polymorphisms at the half-transporter ABCG5 and ABCG8 genes affect blood cholesterol concentrations in prepubertal children by influencing dietary respon- siveness. This highly significant gene–nutrient interaction could explain the great individual differences in the plasma lipid response to cholesterol and fat intake.
    [Show full text]
  • Apolipoprotein B: a Risk-Enhancing Factor in the Primary Prevention of Cardiovascular Disease
    Apolipoprotein B: a Risk-enhancing Factor in the Primary Prevention of Cardiovascular Disease The American College of Cardiologists and the American Heart • elevated high-sensitivity C-reactive Protein (≥ 2.0 mg/L); Association recently issued an updated guideline to help address • elevated Lipoprotein(a) – ≥ 50 mg/dL constitutes risk-enhancing the primary prevention of cardiovascular disease at population and factor; relative indication for measurement is family history of individual patient levels. This 2019 guideline combines existing premature ASCVD; scientific statements, expert consensus, and clinical practice guidelines • elevated Apolipoprotein B (≥ 130 mg/dL constitutes risk- and adds new recommendations for physical activity, aspirin use, enhancing factor; relative indication for measurement is and tobacco use. Suggestions for team-based care, shared decision triglyceride ≥ 200 mg/dL (≥ 130 mg/dL corresponds to LDL-C > making, and assessment of social determinants of health round out a 160 mg/dL). comprehensive but focused approach to primary prevention.1 The role of low-density lipoprotein (LDL) particles has been To enhance clinician-patient discussions and help inform prevention documented to elevate patient risk for ASCVD and is well known in strategies, the guideline advocates, among other things, estimating the development and progression of ASCVD.3 As stated in the Journal an individual’s 10-year risk for atherosclerotic cardiovascular disease of Family Medicine, LDL particles move into the arterial wall via a (ASCVD) to1: gradient-driven process. Once inside the intima, LDL particles that bind to the arterial wall are oxidized and subsequently taken up by • match the intensity of interventions with patient’s risk, macrophages to form foam cells.3 The greater the circulating levels • maximize the expected benefit, and of LDL over time, the greater the acceleration of this process and the • minimize possible harm from overtreatment.
    [Show full text]
  • Apolipoprotein and LRP1-Based Peptides As New Therapeutic Tools in Atherosclerosis
    Journal of Clinical Medicine Review Apolipoprotein and LRP1-Based Peptides as New Therapeutic Tools in Atherosclerosis Aleyda Benitez Amaro 1,2, Angels Solanelles Curco 2, Eduardo Garcia 1,2, Josep Julve 3,4 , Jose Rives 5,6, Sonia Benitez 7,* and Vicenta Llorente Cortes 1,2,8,* 1 Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain; [email protected] (A.B.A.); [email protected] (E.G.) 2 Biomedical Research Institute Sant Pau (IIB-Sant Pau), 08041 Barcelona, Spain; [email protected] 3 Metabolic Basis of Cardiovascular Risk Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain; [email protected] 4 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain 5 Biochemistry Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain; [email protected] 6 Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, 08016 Barcelona, Spain 7 Cardiovascular Biochemistry Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain 8 CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain * Correspondence: [email protected] (S.B.); [email protected] or [email protected] (V.L.C.) Abstract: Apolipoprotein (Apo)-based mimetic peptides have been shown to reduce atherosclerosis. Most of the ApoC-II and ApoE mimetics exert anti-atherosclerotic effects by improving lipid profile. ApoC-II mimetics reverse hypertriglyceridemia and ApoE-based peptides such as Ac-hE18A-NH2 Citation: Benitez Amaro, A.; reduce cholesterol and triglyceride (TG) levels in humans.
    [Show full text]
  • Apolipoprotein A-IV: a Multifunctional Protein Involved in Protection Against Atherosclerosis and Diabetes
    cells Review Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes Jie Qu 1, Chih-Wei Ko 1, Patrick Tso 1 and Aditi Bhargava 2,* 1 Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237-0507, USA; [email protected] (J.Q.); [email protected] (C.-W.K.); [email protected] (P.T.) 2 Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0556, USA * Correspondence: [email protected]; Tel.: +1-415-502-8453 Received: 9 March 2019; Accepted: 2 April 2019; Published: 5 April 2019 Abstract: Apolipoprotein A-IV (apoA-IV) is a lipid-binding protein, which is primarily synthesized in the small intestine, packaged into chylomicrons, and secreted into intestinal lymph during fat absorption. In the circulation, apoA-IV is present on chylomicron remnants, high-density lipoproteins, and also in lipid-free form. ApoA-IV is involved in a myriad of physiological processes such as lipid absorption and metabolism, anti-atherosclerosis, platelet aggregation and thrombosis, glucose homeostasis, and food intake. ApoA-IV deficiency is associated with atherosclerosis and diabetes, which renders it as a potential therapeutic target for treatment of these diseases. While much has been learned about the physiological functions of apoA-IV using rodent models, the action of apoA-IV at the cellular and molecular levels is less understood, let alone apoA-IV-interacting partners. In this review, we will summarize the findings on the molecular function of apoA-IV and apoA-IV-interacting proteins.
    [Show full text]
  • Effects of Dietary Saturated Fat on LDL Subclasses and Apolipoprotein CIII in Men
    European Journal of Clinical Nutrition (2012) 66, 1229–1233 & 2012 Macmillan Publishers Limited All rights reserved 0954-3007/12 www.nature.com/ejcn ORIGINAL ARTICLE Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men N Faghihnia1, LM Mangravite1,2, S Chiu1, N Bergeron1,3 and RM Krauss1 BACKGROUND/OBJECTIVES: Small dense low-density lipoprotein (LDL) particles and apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that can be modulated by diet, but there is little information regarding the effects of dietary saturated fat on their plasma levels. We tested the effects of high vs low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL. SUBJECTS/METHODS: Following consumption of a baseline diet (50% carbohydrate (CHO), 13% protein, 38% total fat, 15% saturated fat) for 3 weeks, 14 healthy men were randomly assigned to two reduced CHO high beef protein diets (31% CHO, 31% protein, 38% fat) that differed in saturated fat content (15% vs 8%) for 3 weeks each in a crossover design. RESULTS: The high saturated fat (HSF) diet resulted in higher mass concentrations of buoyant LDL I, medium density LDL II and dense LDL III, but not the very dense LDL IV; and significant increases in plasma and LDL apoCIII concentration of 9.4% and 33.5%, respectively. The saturated fat-induced changes in LDL apoCIII were specifically correlated with changes in apoCIII content of LDL IV. CONCLUSIONS: Taken together with previous observations, these findings suggest that, at least in the context of a lower CHO high beef protein diet, HSF intake may increase CVD risk by metabolic processes that involve apoCIII.
    [Show full text]
  • The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation
    International Journal of Molecular Sciences Review The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation Virginia Actis Dato 1,2 and Gustavo Alberto Chiabrando 1,2,* 1 Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina; [email protected] 2 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba X5000HUA, Argentina * Correspondence: [email protected]; Tel.: +54-351-4334264 (ext. 3431) Received: 6 May 2018; Accepted: 13 June 2018; Published: 15 June 2018 Abstract: Metabolic syndrome (MetS) is a highly prevalent disorder which can be used to identify individuals with a higher risk for cardiovascular disease and type 2 diabetes. This metabolic syndrome is characterized by a combination of physiological, metabolic, and molecular alterations such as insulin resistance, dyslipidemia, and central obesity. The low-density lipoprotein receptor-related protein 1 (LRP1—A member of the LDL receptor family) is an endocytic and signaling receptor that is expressed in several tissues. It is involved in the clearance of chylomicron remnants from circulation, and has been demonstrated to play a key role in the lipid metabolism at the hepatic level. Recent studies have shown that LRP1 is involved in insulin receptor (IR) trafficking and intracellular signaling activity, which have an impact on the regulation of glucose homeostasis in adipocytes, muscle cells, and brain. In addition, LRP1 has the potential to inhibit or sustain inflammation in macrophages, depending on its cellular expression, as well as the presence of particular types of ligands in the extracellular microenvironment.
    [Show full text]
  • ABCA1) in Human Disease
    International Journal of Molecular Sciences Review The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease Leonor Jacobo-Albavera 1,† , Mayra Domínguez-Pérez 1,† , Diana Jhoseline Medina-Leyte 1,2 , Antonia González-Garrido 1 and Teresa Villarreal-Molina 1,* 1 Laboratorio de Genómica de Enfermedades Cardiovasculares, Dirección de Investigación, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City CP14610, Mexico; [email protected] (L.J.-A.); [email protected] (M.D.-P.); [email protected] (D.J.M.-L.); [email protected] (A.G.-G.) 2 Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM), Coyoacán, Mexico City CP04510, Mexico * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein- cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the Citation: Jacobo-Albavera, L.; pathophysiology of a broad array of diseases. This review describes evidence obtained from animal Domínguez-Pérez, M.; Medina-Leyte, models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, D.J.; González-Garrido, A.; Villarreal- coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related Molina, T.
    [Show full text]
  • The Regulation of Apob Metabolism by Insulin
    TEM-879; No. of Pages 7 Review The regulation of ApoB metabolism by insulin 1 2 1 Mary E. Haas , Alan D. Attie , and Sudha B. Biddinger 1 Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA 2 Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA The leading cause of death in diabetic patients is cardio- are not capable of catabolizing cholesterol. They must vascular disease. Apolipoprotein B (ApoB)-containing therefore return excess cholesterol to the liver, which lipoprotein particles, which are secreted and cleared can secrete cholesterol into the bile, either directly or after by the liver, are essential for the development of athero- conversion to bile acids [5]. sclerosis. Insulin plays a key role in the regulation of Lipoproteins can be divided into classes that vary in ApoB. Insulin decreases ApoB secretion by promoting their apolipoproteins, lipid composition and, therefore, ApoB degradation in the hepatocyte. In parallel, insulin function. Apolipoprotein B is a structural protein that is promotes clearance of circulating ApoB particles by the an integral component of chylomicrons, as well as very low- liver via the low-density lipoprotein receptor (LDLR), density lipoprotein (VLDL), intermediate-density lipopro- LDLR-related protein 1 (LRP1), and heparan sulfate pro- tein (IDL), and low-density lipoprotein (LDL) particles. teoglycans (HSPGs). Consequently, the insulin-resistant Chylomicrons are secreted by the intestine and enable state of type 2 diabetes (T2D) is associated with in- the transport of dietary triglycerides to other tissues after creased secretion and decreased clearance of ApoB. feeding. They contain a truncated form of ApoB, referred to Here, we review the mechanisms by which insulin con- as ApoB48 because it is 48% of the full-length protein [6].
    [Show full text]
  • Remnants of the Triglyceride-Rich Lipoproteins, Diabetes, and Cardiovascular Disease
    508 Diabetes Volume 69, April 2020 Remnants of the Triglyceride-Rich Lipoproteins, Diabetes, and Cardiovascular Disease Alan Chait,1 Henry N. Ginsberg,2 Tomas Vaisar,1 Jay W. Heinecke,1 Ira J. Goldberg,3 and Karin E. Bornfeldt1,4 Diabetes 2020;69:508–516 | https://doi.org/10.2337/dbi19-0007 Diabetes is now a pandemic disease. Moreover, a large LDL-C levels by increasing LDL receptor activity are widely number of people with prediabetes are at risk for de- used to prevent CVD. However, despite the benefitof veloping frank diabetes worldwide. Both type 1 and type statins and marked reduction of circulating LDL-C levels, 2 diabetes increase the risk of atherosclerotic cardio- patients with diabetes continue to have more CVD events vascular disease (CVD). Even with statin treatment to than patients without diabetes, indicating significant re- lower LDL cholesterol, patients with diabetes have a high sidual CVD risk. A recent new classification system of residual CVD risk. Factors mediating the residual risk are T2DM, based on different patient characteristics and risk of incompletely characterized. An attractive hypothesis is diabetes complications, divides adults into five different that remnant lipoprotein particles (RLPs), derived by clusters of diabetes (3). Such a substratification of T2DM, lipolysis from VLDL and chylomicrons, contribute to this which takes insulin resistance and several other factors into residual risk. RLPs constitute a heterogeneous popula- account, could perhaps help tailor treatment to those who tion of lipoprotein particles, varying markedly in size and would benefit the most. composition. Although a universally accepted definition fi There are likely to be a number of reasons why cho- is lacking, for the purpose of this review we de ne RLPs fi as postlipolytic partially triglyceride-depleted particles lesterol reduction in patients with diabetes is not suf cient derived from chylomicrons and VLDL that are relatively to reduce CVD events to the levels found in patients enriched in cholesteryl esters and apolipoprotein (apo)E.
    [Show full text]