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      The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index

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          Abstract

          Cardiovascular disease (CVD) events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. The number and severity of CVD events remain inappropriate and difficult to explain by considering only the classic CVD risk factors. Our aim was to clarify the changes and the relationship of lipoprotein subfractions with other CVD risk factors, namely, body mass index (BMI) and adipokines, inflammation and low-density lipoprotein (LDL) oxidation, and the burden of the most prevalent comorbidities, diabetes mellitus (DM) and hypertension (HT). We studied 194 ESRD patients on dialysis and 22 controls; lipid profile, including lipoprotein subpopulations and oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, leptin, and paraoxonase 1 activity were evaluated. Compared to controls, patients presented significantly lower levels of cholesterol, high-density lipoprotein cholesterol (HDLc), LDLc, oxLDL, and intermediate and small HDL and higher triglycerides, CRP, adiponectin, large HDL, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein- (IDL) B. Adiponectin levels correlated positively with large HDL and negatively with intermediate and small HDL, oxLDL/LDLc, and BMI; patients with DM ( n = 17) and with DM+HT ( n = 70), as compared to patients without DM or HT ( n = 69) or only with HT ( n = 38), presented significantly higher oxLDL, oxLDL/LDLc, and leptin and lower adiponectin. Obese patients ( n = 45), as compared to normoponderal patients ( n = 81), showed lower HDLc, adiponectin, and large HDL and significantly higher leptin, VLDL, and intermediate and small HDL. In ESRD, the higher adiponectin seems to favor atheroprotective HDL modifications and protect LDL particles from oxidative atherogenic changes. However, in diabetic and obese patients, adiponectin presents the lowest values, oxLDL/LDLc present the highest ones, and the HDL profile is the more atherogenic. Our data suggest that the coexistence of DM and adiposity in ESRD patients on dialysis contributes to a higher CVD risk, as showed by their lipid and adipokine profiles.

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          A Two-Step Approach for Transforming Continuous Variables to Normal: Implications and Recommendations for IS Research

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            The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults?

            Hypertrophic obesity correlates with metabolic complications of obesity. We evaluated adipocyte volume and its relationship with tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), adiponectin and high sensitivity C-reactive protein (hs-CRP) levels. Patients were divided into 4 groups; lean healthy controls [body mass index (BMI): 24.2+/-1.4 kg/m2], non-diabetic obese patients (30.2+/-2.9), obese (30.1+/-3.2) and non-obese (22.2+/-1.5) Type 2 diabetic patients. TNF-alpha, hs-CRP, adiponectin and IL-6 levels were measured preoperatively and sc fat specimens were obtained during operation. Semi-thin sections were stained with toluidine-blue and evaluated by light microscopy. Fat volumes were calculated by Goldrick's formulation. Mean adipocyte volumes were higher in obese diabetic patients than in other groups (p<0.0001). Mean TNF-alpha, hs-CRP and IL-6 levels were higher in obese diabetic patients than in control subjects, obese non-diabetic and non-obese diabetic patients (p<0.0001, p<0.02 and p<0.01, respectively). Mean TNF-alpha levels of non-diabetic obese patients were higher than the control group (p<0.05). Mean IL-6 levels of diabetic and non-diabetic obese patients were higher than control subjects (p<0.02 and p<0.0001, respectively). Mean adiponectin levels of control subjects were higher than non-diabetic obese, non-obese diabetic and obese-diabetic subjects (p<0.0001). Mean adiponectin levels of obese diabetic patients were lower than non-diabetic obese subjects (p<0.008). Mean hs-CRP levels were higher in diabetic patients whether they were obese or not. There was a positive correlation between adipocyte size and TNF-alpha (p<0.01), IL-6 (p<0.03) and hs-CRP levels (p<0.004), and negative correlation between adipocyte size, adiponectin levels (p<0.0001). TNF-alpha, IL-6 and hs-CRP levels were positively, adiponectin negatively correlated with adipocyte size. Therefore, adiposity may be an inflammatory condition.
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              Uremia alters HDL composition and function.

              Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood. Here, we used mass spectrometry and biochemical analyses to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis. We identified a significant increase in the amount of acute phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A2, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipid and increased triglyceride and lysophospholipid. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages. In summary, the altered composition of HDL in renal disease seems to inhibit its cardioprotective properties. Assessing HDL composition and function in renal disease may help identify patients at increased risk for cardiovascular disease.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2019
                18 February 2019
                : 2019
                : 3021785
                Affiliations
                1UCIBIO/REQUIMTE, Porto, Portugal
                2CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Gandra-Paredes, Portugal
                3Institute of Pharmacology & Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, CNC.IBILI Consortium & CIBB Consortium, University of Coimbra, Coimbra, Portugal
                4Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, Coimbra, Portugal
                5UCIBIO/REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
                6Health Science Research Centre, University of Beira Interior, Covilhã, Portugal
                7Hemodialysis Clinic Hospital Agostinho Ribeiro, Felgueiras, Portugal
                8Hemodialysis Clinic of Porto (CHP), Porto, Portugal
                9Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Porto, Portugal
                10NefroServe, Hemodialysis Clinic of Barcelos, Barcelos, Portugal
                11NefroServe Hemodialysis Clinic of Viana do Castelo, Viana do Castelo, Portugal
                12Hemodialysis Clinic of Gondomar, Gondomar, Portugal
                Author notes

                Academic Editor: Fawzy Elbarbry

                Author information
                http://orcid.org/0000-0001-8411-8038
                http://orcid.org/0000-0003-3401-9554
                http://orcid.org/0000-0002-1316-1319
                http://orcid.org/0000-0001-6162-2426
                http://orcid.org/0000-0002-3571-2513
                http://orcid.org/0000-0002-8061-9289
                http://orcid.org/0000-0002-3941-6850
                http://orcid.org/0000-0002-2565-3169
                Article
                10.1155/2019/3021785
                6397972
                30911344
                c4452006-38a5-41e0-a37f-88aecfaa0f9f
                Copyright © 2019 Susana Coimbra et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 October 2018
                : 10 December 2018
                Funding
                Funded by: Fundação para a Ciência e a Tecnologia
                Funded by: European Regional Development Fund
                Funded by: UCIBIO
                Award ID: UID/MULTI/04378/2013-POCI/01/0145/FEDER/007728
                Funded by: North Portugal Regional Coordination and Development Commission
                Award ID: Norte-01-0145-FEDER-000024
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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