Serum Metabolite Profiles and Target Tissue Gene Expression Define the Effect of Cholecalciferol Intake on Calcium Metabolism in Rats and Mice

Abstract

We studied the effect of cholecalciferol (VD3) intake on VD3 status and markers of calcium (Ca) homeostasis in mice and rats. Serum 25 hydroxycholecalciferol (25OH-VD3) concentrations were increased in animals fed diets containing 400-20,000 international units (IU) VD3/kg (37 nmol.L(-1).1000 IU VD3(-1)), but body weight, serum Ca, and duodenal gene expression were not altered. High-VD3 intake decreased serum 1, 25-dihydroxycholecalciferol [1,25(OH)2-VD3] and renal 25 hydroxycholecalciferol-1alphahydroxylase (CYP27B1) mRNA, suggesting that rodents tolerate high-VD3 intake by suppressing the activity of the VD3 endocrine system. Serum 25OH-VD3 declined when animals were fed diets containing 1000 to 25 IU VD3/kg (9-11 wk, inflection at 200 IU/kg, 4-fold steeper slope below this). Neither body weight nor serum Ca were influenced by low-VD3 intake. However, mice fed the 25-IU/kg diet had lower serum 1,25(OH)2-VD3, duodenal calbindin D9k mRNA, bone mineral density, and renal 25 hydroxycholecalciferol-24 hydroxylase mRNA, whereas renal CYP27B1 mRNA was elevated when rodents were fed < 200 IU VD3/kg. These data reveal a stress on VD3 and Ca metabolism at low dietary VD3 intake. Dietary Ca restriction (0.25 vs. 0.5%, 9 wk) increased serum 1,25(OH)2-VD3 and was 30% greater in rats fed a 10,000-IU VD3/kg diet. High-VD3 intake did not prevent Ca restriction-induced bone loss. Our data show that modeling human VD3 status requires lower intake than the current NRC rodent requirement (1000-IU/kg diet). Also, although rodents are very tolerant of high-VD3 intake, it cannot compensate for moderate Ca restriction.

Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation

“…This concentration has been reported as being non toxic to rodents, without major risk of hypercalcemia [27]. Consecutively to the supplementation in mice, we observed an increase of 25(OH)D plasma level, as previously reported [27]. Interestingly, we…”

“…The present results were obtained with 15000 IU of VD3/kg of food, which corresponds to about 10 times the usual VD supply for laboratory rodents (1500 IU of VD3/ kg of food in diet used as control). This concentration has been reported as being non toxic to rodents, without major risk of hypercalcemia [27]. Consecutively to the supplementation in mice, we observed an increase of 25(OH)D plasma level, as previously reported [27].…”

Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

“…Second, the behavioral task used here, assessing hippocampal-dependent spatial memory, also has relevance for human memory because patients with hippocampal lesions perform poorly in a virtual maze test (47,48). Finally, the vitamin D levels achieved here model clinically relevant levels found in humans, ranging from deficient to sufficient (70,83,84), and animals with the highest 25OHD levels, considered "optimal" by some recommendations (5,(85)(86)(87)(88), outperformed animals with lower levels on a challenging cognitive task.…”

Consequências sistêmicas da cirurgia bariátrica e suas repercussões na saúde bucal

“…Vitamin D is essential to maintain normal calcium metabolism 52 . In case of vitamin D deficiency, calcium absorption is insufficient failing to maintain the body's needs, may lead to secondary hyperparathyroidism 18,39,42,46,52 which is an increase of production of parathyroid hormone, besides the removal of calcium from bone and reabsorption in the kidneys to maintain their normal levels. Osteoporosis was found in 26.3% of 180 patients with vitamin D deficiency assessed by Silva et al 50 .…”

“…A disease caused by a deficiency in adults promotes hypocalcemia and secondary hyperparathyroidism with subsequent loss of trabecular bone and thinning of cortical bone, which leads to increased risk of fractures 41 . The diagnosis of bone loss has been reported in some cases 18,39,42,46 . Bone loss associated with bariatric surgery was proven by Fleischer et al 39 who evaluated 23 obese men and women, 20 to 64 years.…”