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 ∼75% in the jejunum and decreased
the concentration of serum fructose by ∼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.