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      The Role of Overweight and Obesity in the Cardiorenal Syndrome

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          Abstract

          The presence of a group of interactive maladaptive factors including hypertension, insulin resistance, metabolic dyslipidemia, obesity, microalbuminuria, and/or reduced renal function constitute the cardiorenal metabolic syndrome (CRS). Overweight, obesity, and chronic kidney disease (CKD) have grown to pandemic proportions in industrialized countries during the past decade. The fact that these interactive factors promote heart and renal disease has been documented in large population-based studies. Obesity seems to be the driving force behind the development of heart disease and CKD and therefore the CRS. The relationship between overweight/obesity and kidney disease begins in early childhood and appears to be related to overconsumption of high-fructose corn syrup and insufficient physical activity. Today, 13 million children are obese, and over 70% of these children are likely to become obese adults. Indeed, approximately 30% of male and 34% of female adults in the United States are obese. This lifestyle-related epidemic will be a major societal medical and economic problem that will accentuate the current epidemic of CKD in the United States and other industrialized and emerging industrialized countries. In this article, we will review the potential mechanisms by which obesity and other metabolic abnormalities interact to promote heart and progressive kidney disease.

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          A causal role for uric acid in fructose-induced metabolic syndrome.

          The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.
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            High body mass index for age among US children and adolescents, 2003-2006.

            The prevalence of overweight among US children and adolescents increased between 1980 and 2004. To estimate the prevalence of 3 measures of high body mass index (BMI) for age (calculated as weight in kilograms divided by height in meters squared) and to examine recent trends for US children and adolescents using national data with measured heights and weights. Height and weight measurements were obtained from 8165 children and adolescents as part of the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey (NHANES), nationally representative surveys of the US civilian, noninstitutionalized population. Prevalence of BMI for age at or above the 97th percentile, at or above the 95th percentile, and at or above the 85th percentile of the 2000 sex-specific Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts among US children by age, sex, and racial/ethnic group. Because no statistically significant differences in the prevalence of high BMI for age were found between estimates for 2003-2004 and 2005-2006, data for the 4 years were combined to provide more stable estimates for the most recent time period. Overall, in 2003-2006, 11.3% (95% confidence interval [CI], 9.7%-12.9%) of children and adolescents aged 2 through 19 years were at or above the 97th percentile of the 2000 BMI-for-age growth charts, 16.3% (95% CI, 14.5%-18.1%) were at or above the 95th percentile, and 31.9% (95% CI, 29.4%-34.4%) were at or above the 85th percentile. Prevalence estimates varied by age and by racial/ethnic group. Analyses of the trends in high BMI for age showed no statistically significant trend over the 4 time periods (1999-2000, 2001-2002, 2003-2004, and 2005-2006) for either boys or girls (P values between .07 and .41). The prevalence of high BMI for age among children and adolescents showed no significant changes between 2003-2004 and 2005-2006 and no significant trends between 1999 and 2006.
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              Role of oxidative stress in cardiac hypertrophy and remodeling.

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                Author and article information

                Journal
                CRM
                Cardiorenal Med
                10.1159/issn.1664-5502
                Cardiorenal Medicine
                S. Karger AG
                1664-3828
                1664-5502
                2011
                January 2011
                17 January 2011
                : 1
                : 1
                : 5-12
                Affiliations
                aDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, bDepartment of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, cDiabetes and Cardiovascular Center, and dHarry S. Truman VA Medical Center, Columbia, Mo., USA
                Author notes
                *James R. Sowers, MD, D109 Diabetes Center, UHC, One Hospital Drive, Columbia, MO 65212 (USA), Tel. +1 573 882 0999, Fax +1 573 884 5530, E-Mail sowersj@health.missouri.edu
                Article
                322822 PMC3101516 Cardiorenal Med 2011;1:5–12
                10.1159/000322822
                PMC3101516
                22258461
                67762c05-d5ae-4b2c-b722-bd21c85d214b
                © 2011 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 1, Tables: 1, Pages: 8
                Categories
                Review

                Cardiovascular Medicine,Nephrology
                Adiposity,Cardiorenal metabolic syndrome,Chronic kidney disease,Heart failure,Metabolic dyslipidemia,Obesity

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