title: Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9.
abstract: Excess circulating uric acid, a product of hepatic glycolysis and purine metabolism, often accompanies metabolic syndrome. However, whether hyperuricaemia contributes to the development of metabolic syndrome or is merely a by-product of other processes that cause this disorder has not been resolved. In addition, how uric acid is cleared from the circulation is incompletely understood. Here we present a genetic model of spontaneous, early-onset metabolic syndrome in mice lacking the enterocyte urate transporter Glut9 (encoded by the SLC2A9 gene). Glut9-deficient mice develop impaired enterocyte uric acid transport kinetics, hyperuricaemia, hyperuricosuria, spontaneous hypertension, dyslipidaemia and elevated body fat. Allopurinol, a xanthine oxidase inhibitor, can reverse the hypertension and hypercholesterolaemia. These data provide evidence that hyperuricaemia per se could have deleterious metabolic sequelae. Moreover, these findings suggest that enterocytes may regulate whole-body metabolism, and that enterocyte urate metabolism could potentially be targeted to modulate or prevent metabolic syndrome.
authors.affiliation: BJC Institute of Health, Washington University School of Medicine, 10th Floor 425 S., Euclid Avenue Campus, Box 8064, St Louis, MO 63110, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: DeBosch
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kluth
authors.affiliation: BJC Institute of Health, Washington University School of Medicine, 10th Floor 425 S., Euclid Avenue Campus, Box 8064, St Louis, MO 63110, USA.
authors.forename: Hideji
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
authors.affiliation: BJC Institute of Health, Washington University School of Medicine, 10th Floor 425 S., Euclid Avenue Campus, Box 8064, St Louis, MO 63110, USA.
authors.forename: Kelle
authors.initials: K
authors.lastname: Moley
mesh_terms: D000493:Allopurinol / Q000737:chemistry; D000818:Animals; D001823:Body Composition; D002151:Calorimetry; D004452:Echocardiography; D020895:Enterocytes / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics* / Q000378:metabolism; D033461:Hyperuricemia / Q000378:metabolism / Q000503:physiopathology*; D024821:Metabolic Syndrome / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014527:Uric Acid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C498775:Slc2a9 protein, mouse; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase
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