title: Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension.
abstract: The identity of the transporter responsible for fructose absorption in the intestine in vivo and its potential role in fructose-induced hypertension remain speculative. Here we demonstrate that Glut5 (Slc2a5) deletion reduced fructose absorption by approximately 75% in the jejunum and decreased the concentration of serum fructose by approximately 90% relative to wild-type mice on increased dietary fructose. When fed a control (60% starch) diet, Glut5(-/-) mice had normal blood pressure and displayed normal weight gain. However, whereas Glut5(+/+) mice showed enhanced salt absorption in their jejuna in response to luminal fructose and developed systemic hypertension when fed a high fructose (60% fructose) diet for 14 weeks, Glut5(-/-) mice did not display fructose-stimulated salt absorption in their jejuna, and they experienced a significant impairment of nutrient absorption in their intestine with accompanying hypotension as early as 3-5 days after the start of a high fructose diet. Examination of the intestinal tract of Glut5(-/-) mice fed a high fructose diet revealed massive dilatation of the caecum and colon, consistent with severe malabsorption, along with a unique adaptive up-regulation of ion transporters. In contrast to the malabsorption of fructose, Glut5(-/-) mice did not exhibit an absorption defect when fed a high glucose (60% glucose) diet. We conclude that Glut5 is essential for the absorption of fructose in the intestine and plays a fundamental role in the generation of fructose-induced hypertension. Deletion of Glut5 results in a serious nutrient-absorptive defect and volume depletion only when the animals are fed a high fructose diet and is associated with compensatory adaptive up-regulation of ion-absorbing transporters in the colon.
authors.affiliation: Center on Genetics of Transport and Epithelial Biology and the Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Barone
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Fussell
authors.forename: Anurag Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Fred
authors.initials: F
authors.lastname: Lucas
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Charles
authors.initials: C
authors.lastname: Kim
authors.forename: Xudong
authors.initials: X
authors.lastname: Wu
authors.forename: Yiling
authors.initials: Y
authors.lastname: Yu
authors.forename: Hassane
authors.initials: H
authors.lastname: Amlal
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Manoocher
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D004032:Diet / Q000009:adverse effects; D005632:Fructose / Q000009:adverse effects* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects* / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D013213:Starch / Q000494:pharmacology; D013549:Sweetening Agents / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051296:Glucose Transporter Type 5; C495726:SLC2A5 protein, human; C465351:Slc2a5 protein, mouse; D013549:Sweetening Agents; D005632:Fructose; D013213:Starch; D005947:Glucose