title: 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.
authors.affiliation: Department of Foods and Nutrition and the Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907-2059, USA. fleet@purdue.edu
authors.forename: James C
authors.initials: JC
authors.lastname: Fleet
authors.forename: Christy
authors.initials: C
authors.lastname: Gliniak
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yingben
authors.initials: Y
authors.lastname: Xue
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Smith
authors.forename: Rebecca
authors.initials: R
authors.lastname: McCreedy
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Adedokun
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000494:pharmacology*; D002762:Cholecalciferol / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*; D004032:Diet; D005260:Female; D005269:Femur / Q000737:chemistry / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006887:Hydroxycholecalciferols / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D002136:Calcium, Dietary; D006887:Hydroxycholecalciferols; D012333:RNA, Messenger; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium