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)₂D₃. Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets fromd2of gestation to the end of lactation. Compared to virgins, lactating dams fed glucose or starch had higher rates of intestinal transcellular Ca²⁺ transport, elevated intestinal and renal expression of Ca²⁺ channels, Ca²⁺-binding proteins, and CaATPases, as well as increased levels of 25-(OH)D₃ and 1,25-(OH)₂D₃. 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) ₂D₃level 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 Ca²⁺ requirements increase during lactation or similar physiologically challenging conditions, excessive fructose consumption may perturb Ca²⁺ homeostasis because of fructose-induced reductions in synthesis of 1,25-(OH)₂D₃.