Document Detail


A causal role for uric acid in fructose-induced metabolic syndrome.
MedLine Citation:
PMID:  16234313     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Takahiko Nakagawa; Hanbo Hu; Sergey Zharikov; Katherine R Tuttle; Robert A Short; Olena Glushakova; Xiaosen Ouyang; Daniel I Feig; Edward R Block; Jaime Herrera-Acosta; Jawaharlal M Patel; Richard J Johnson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-10-18
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  290     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-07     Completed Date:  2006-04-10     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F625-31     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Hypertension, and Transplantation, PO Box 100224, University of Florida, Gainesville, FL 32610, USA. nakagt@medicine.ufl.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Fructose / toxicity*
Male
Metabolic Syndrome X / blood*,  chemically induced
Rats
Rats, Sprague-Dawley
Triglycerides / blood
Uric Acid / blood*
Grant Support
ID/Acronym/Agency:
DK 52121/DK/NIDDK NIH HHS; HL 68607/HL/NHLBI NIH HHS; P50 DK 064233/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Triglycerides; 30237-26-4/Fructose; 69-93-2/Uric Acid

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