Endocrine Abstracts

An adequate intestinal uptake of calcium is critical for the maintenance of calcium homeostasis during pregnancy and lactation. We previously found in rat models of end-stage renal disease that dietary fructose reduces intestinal calcium absorption and perturbs kidney morphology. Despite the dramatic rise in fructose consumption and the evidence of its deleterious effects for adult health, there is no information about fructose effects on maternal health and pregnancy outcomes. We investigated the interactions between pregnancy/lactation and dietary fructose, to evaluate if fructose compromises intestinal calcium absorption and homeostasis and whether calcitriol (active form of vitamin D and one of the main regulators of calcium transport) mediates this effect. Three groups of pregnant rats and virgin controls were fed isocaloric 63% glucose, fructose or starch diets during gestation and lactation. Excessive fructose intake prevents lactation-induced increases in intestinal calcium transport, in intestinal expression of calcium transporting and binding proteins (TRPV6 and CaBP9k), and in calcitriol plasma level. The binding of VDR, the transcription factor mediating the activity of calcitriol_, to the promoters of TRPV6 and CaBP9k genes was also significantly reduced in dams fed fructose. Changes in calcitriol levels were tightly correlated with alterations in expression of the 1α-hydroxylase but not 24-hydroxylase, indicating that excessive fructose intake perturbs specifically the final step in calcitriol synthesis. Bone mineral density and content as well as mechanical strength decrease with lactation, and dietary fructose and glucose significantly exacerbate these effects. Thus, we showed that over-consumption of fructose during pregnancy and lactation impairs renal production of calcitriol which leads to a decrease in active intestinal calcium transport due to lowered expression of calcium transporters in duodenum. These results are all the more important since there is evidence that the current daily recommendations for vitamin D intake may be inadequate to ensure calcitriol sufficiency in humans.