title: Excessive fructose intake causes 1,25-(OH)(2)D(3)-dependent inhibition of intestinal and renal calcium transport in growing rats.
abstract: We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca(2+) transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca(2+) absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca(2+) transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca(2+) transport rate as well as in expression of intestinal and renal Ca(2+) transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca(2+) transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca(2+) transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca(2+) and vitamin D deficiency.
authors.affiliation: Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark, New Jersey;
authors.forename: Veronique
authors.initials: V
authors.lastname: Douard
authors.forename: Yves
authors.initials: Y
authors.lastname: Sabbagh
authors.forename: Jacklyn
authors.initials: J
authors.lastname: Lee
authors.forename: Chirag
authors.initials: C
authors.lastname: Patel
authors.forename: Francis W
authors.initials: FW
authors.lastname: Kemp
authors.forename: John D
authors.initials: JD
authors.lastname: Bogden
authors.forename: Sheldon
authors.initials: S
authors.lastname: Lin
authors.forename: Ronaldo P
authors.initials: RP
authors.lastname: Ferraris
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000367:Age Factors; D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005632:Fructose / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005937:Glucaric Acid / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics; D014808:Vitamin D Deficiency / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D005632:Fructose; D013250:Steroid Hydroxylases; C585551:Cyp24a1 protein, rat; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D005937:Glucaric Acid; D002118:Calcium
keywords: FGF23; bone; growth; intestine; kidney; parathyroid hormone; vitamin D