Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5.
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.
Singh
Anurag Kumar
AK
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Amlal
Hassane
H
Haas
Patrick J
PJ
Dringenberg
Ulrike
U
Fussell
Stacey
S
Barone
Sharon L
SL
Engelhardt
Regina
R
Zuo
Jian
J
Seidler
Ursula
U
Soleimani
Manoocher
M
D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D004032:Diet; D005260:Female; D005632:Fructose / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D002712:Chlorides; D051246:Glucose Transport Proteins, Facilitative; D051296:Glucose Transporter Type 5; C465351:Slc2a5 protein, mouse; C495727:Slc2a5 protein, rat; C483904:Slc36a1 protein, mouse; C493537:Slc36a1 protein, rat; D027981:Symporters; D005632:Fructose