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      Is the Retinol-Binding Protein 4 a Possible Risk Factor for Cardiovascular Diseases in Obesity?

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          Abstract

          Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group. In our review, we summarized the current knowledge about RBP4 and its association with essential aspects of cardiovascular disease—lipid profile, intima-media thickness, atherosclerotic process, and diet. We also discussed the RBP4 gene polymorphisms essential from a cardiovascular perspective.

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          European Society of Cardiology: Cardiovascular Disease Statistics 2019

          The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest.
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            Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.

            Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance. We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes. Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated. RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels. Copyright 2006 Massachusetts Medical Society.
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              Obesity and cardiovascular disease: revisiting an old relationship

              A wealth of clinical and epidemiological evidence has linked obesity to a broad spectrum of cardiovascular diseases (CVD) including coronary heart disease, heart failure, hypertension, stroke, atrial fibrillation and sudden cardiac death. Obesity can increase CVD morbidity and mortality directly and indirectly. Direct effects are mediated by obesity-induced structural and functional adaptations of the cardiovascular system to accommodate excess body weight, as well as by adipokine effects on inflammation and vascular homeostasis. Indirect effects are mediated by co-existing CVD risk factors such as insulin resistance, hyperglycemia, hypertension and dyslipidemia. Adipose tissue (AT) quality and functionality are more relevant aspects for cardiometabolic risk than its total amount. The consequences of maladaptive AT expansion in obesity are local and systemic: the local include inflammation, hypoxia, dysregulated adipokine secretion and impaired mitochondrial function; the systemic comprise insulin resistance, abnormal glucose/lipid metabolism, hypertension, a pro-inflammatory and pro-thrombotic state and endothelial dysfunction, all of which provide linking mechanisms for the association between obesity and CVD. The present narrative review summarizes the major pathophysiological links between obesity and CVD (traditional and novel concepts), analyses the heterogeneity of obesity-related cardiometabolic consequences, and provides an overview of the cardiovascular impact of weight loss interventions.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                23 July 2020
                August 2020
                : 21
                : 15
                : 5229
                Affiliations
                [1 ]Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland; piotr.eder@ 123456op.pl (P.E.); aga.zawada@ 123456gmail.com (A.Z.); alicjaewaratajczak@ 123456gmail.com (A.E.R.); agdob@ 123456ump.edu.pl (A.D.); krela@ 123456op.pl (I.K.-K.)
                [2 ]Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland; mskrzypczakzielinska@ 123456gmail.com (M.S.-Z.); zielinska-aleksandra@ 123456wp.pl (A.Z.)
                [3 ]Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; souto.eliana@ 123456gmail.com
                [4 ]CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
                Author notes
                [* ]Correspondence: a.m.rychter@ 123456gmail.com ; Tel.: +48-8691-343; Fax: +48-8691-686
                Author information
                https://orcid.org/0000-0002-6586-3611
                https://orcid.org/0000-0001-5313-107X
                https://orcid.org/0000-0003-2603-1377
                https://orcid.org/0000-0001-9306-5038
                https://orcid.org/0000-0002-9737-6017
                https://orcid.org/0000-0001-6995-090X
                https://orcid.org/0000-0002-7731-6965
                https://orcid.org/0000-0002-3647-5070
                https://orcid.org/0000-0001-5122-8003
                Article
                ijms-21-05229
                10.3390/ijms21155229
                7432399
                32718041
                14d7ba14-5e4c-44c6-a748-03f892d2c59b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 July 2020
                : 22 July 2020
                Categories
                Review

                Molecular biology
                atherosclerosis,rbp4,cardiovascular disease,obesity,metabolic syndrome,lipoprotein metabolism

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