1. ¹Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
2. ²Department of Medicine, Center on Genetics of Transport and Epithelial Biology, University of Cincinnati, Cincinnati, Ohio, USA
3. ³Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee, USA
4. ⁴Research Services Department, Veterans Affairs Medical Center, Cincinnati, Ohio, USA

Correspondence: Manoocher Soleimani, Department of Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, MSB G259, Cincinnati, OH, USA. E-mail: Manoocher.Soleimani@uc.edu

⁵These authors contributed equally to this work.

Received 31 October 2007; Revised 13 February 2008; Accepted 19 February 2008; Published online 21 May 2008.

Abstract

Increased dietary fructose in rodents recapitulates many aspects of the Metabolic Syndrome with hypertension, insulin resistance and dyslipidemia. Here we show that fructose increased jejunal NaCl and water absorption which was significantly decreased in mice whose apical chloride/base exchanger Slc26a6 (PAT1, CFEX) was knocked out. Increased dietary fructose intake enhanced expression of this transporter as well as the fructose-absorbing transporter Slc2a5 (Glut5) in the small intestine of wild type mice. Fructose feeding decreased salt excretion by the kidney and resulted in hypertension, a response almost abolished in the knockout mice. In parallel studies, a chloride-free diet blocked fructose-induced hypertension in Sprague Dawley rats. Serum uric acid remained unchanged in animals on increased fructose intake with hypertension. We suggest that fructose-induced hypertension is likely caused by increased salt absorption by the intestine and kidney and the transporters Slc26a6 and Slc2a5 are essential in this process.