Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)₂D₃ synthesis and calcium transport.
We recently showed that excessive fructose consumption, already associated with numerous metabolic abnormalities, reduces rates of intestinal Ca(2+) transport. Using a rat lactation model with increased Ca(2+) requirements, we tested the hypothesis that mechanisms underlying these inhibitory effects of fructose involve reductions in renal synthesis of 1,25-(OH)(2)D(3). Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Compared to virgins, lactating dams fed glucose or starch had higher rates of intestinal transcellular Ca(2+) transport, elevated intestinal and renal expression of Ca(2+) channels, Ca(2+)-binding proteins, and CaATPases, as well as increased levels of 25-(OH)D(3) and 1,25-(OH)(2)D(3). Fructose consumption prevented almost all of these lactation-induced increases, and reduced vitamin D receptor binding to promoter regions of Ca(2+) channels and binding proteins. Changes in 1,25-(OH)(2)D(3) level were tightly correlated with alterations in expression of 1α-hydroxylase but not with levels of parathyroid hormone and of 24-hydroxylase. Bone mineral density, content, and mechanical strength each decreased with lactation, but then fructose exacerbated these effects. When Ca(2+) requirements increase during lactation or similar physiologically challenging conditions, excessive fructose consumption may perturb Ca(2+) homeostasis because of fructose-induced reductions in synthesis of 1,25-(OH)(2)D(3).
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07101-1709, USA.
Veronique
V
Douard
Takuji
T
Suzuki
Yves
Y
Sabbagh
Jacklyn
J
Lee
Sue
S
Shapses
Sheldon
S
Lin
Ronaldo P
RP
Ferraris
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000209:etiology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000096:biosynthesis*; D020013:Calcium Signaling / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D006657:Histones / Q000378:metabolism; D006984:Hypertrophy; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007774:Lactation / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism; D013549:Sweetening Agents / Q000008:administration & dosage / Q000009:adverse effects; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
D002135:Calcium-Binding Proteins; D004040:Dietary Carbohydrates; D006657:Histones; D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D013549:Sweetening Agents; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D005632:Fructose; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol