title: Gene-by-diet interactions influence calcium absorption and bone density in mice.
abstract: Dietary calcium (Ca) intake is needed to attain peak bone mineral density (BMD). Habitual low Ca intake increases intestinal Ca absorption efficiency to protect bone mass, but the mechanism controlling, and the impact of genetics on, this adaptive response is not clear. We fed 11 genetically diverse inbred mouse lines a normal (0.5%) or low (0.25%) Ca diet from 4 to 12 weeks of age (n = 8 per diet per line) and studied the independent and interacting effects of diet and genetics on Ca and bone metabolism. Significant genetic variation was observed in all bone, renal, and intestinal phenotypes measured including Ca absorption. Also, adaptation of Ca absorption and bone parameters to low dietary Ca was significantly different among the lines. Ca absorption was positively correlated to femur BMD (r = 0.17, p = 0.02), and distal femur bone volume/tissue volume (BV/TV) (r = 0.34, p < 0.0001). Although Ca absorption was correlated to 1,25 dihydroxyvitamin D (1,25(OH)2 D) (r = 0.35, p < 0.0001), the adaptation of Ca absorption to low Ca intake did not correlate to diet-induced adaptation of 1,25(OH)2 D across the 11 lines. Several intestinal proteins have been proposed to mediate Ca absorption: claudins 2 and 12, voltage gated Ca channel v1.3 (Cav1.3), plasma membrane Ca ATPase 1b (PMCA1b), transient receptor potential vanilloid member 6 (TRPV6), and calbindin D9k (CaBPD9k). Only the mRNA levels for TRPV6, CaBPD9k, and PMCA1b were related to Ca absorption (r = 0.42, 0.43, and 0.21, respectively). However, a significant amount of the variation in Ca absorption is not explained by the current model and suggests that novel mechanisms remain to be determined. These observations lay the groundwork for discovery-focused initiatives to identify novel genetic factors controlling gene-by-diet interactions affecting Ca/bone metabolism.
authors: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
authors: Rebecca A
authors: RA
authors: Replogle
authors: Qiang
authors: Q
authors: Li
authors: Libo
authors: L
authors: Wang
authors: Min
authors: M
authors: Zhang
authors: James C
authors: JC
authors: Fleet
mesh_terms: D000818:Animals; D015519:Bone Density; D002136:Calcium, Dietary / Q000378:metabolism*; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002136:Calcium, Dietary; D012333:RNA, Messenger
keywords: BONE; CALCIUM; DIET; GENETICS; INTESTINAL ABSORPTION
references: Endocrinology. 2007 Mar;148(3):1396-402
references: 17110426
references: Mamm Genome. 2007 Jul;18(6-7):473-81
references: 17674098
references: Gastroenterology. 2009 Apr;136(4):1317-27, e1-2
references: 19254681
references: Am J Clin Nutr. 2010 Oct;92(4):835-40
references: 20660223
references: Am J Physiol Gastrointest Liver Physiol. 2002 Jan;282(1):G130-6
references: 11751166
references: Hum Genet. 2010 Nov;128(5):549-56
references: 20809279
references: Annu Rev Nutr. 1993;13:287-316
references: 8369148
references: Endocrinology. 2008 Jun;149(6):3196-205
references: 18325990
references: J Bone Miner Res. 2003 Sep;18(9):1650-6
references: 12968674
references: Am J Clin Nutr. 2007 Jun;85(6):1657-63
references: 17556706
references: Osteoporos Int. 2004 Jan;15(1):27-31
references: 14598024
references: Endocrinology. 2003 Sep;144(9):3885-94
references: 12933662
references: J Nucl Med. 1973 Oct;14(10):760-2
references: 4743584
references: J Clin Endocrinol Metab. 2003 Mar;88(3):1043-7
references: 12629083
references: Crit Rev Clin Lab Sci. 2010 Aug;47(4):181-95
references: 21182397
references: J Biol Chem. 2004 Dec 10;279(50):52406-13
references: 15456794
references: J Bone Miner Res. 2005 May;20(5):748-57
references: 15824847
references: J Bone Miner Res. 2010 Aug;25(8):1808-20
references: 20200990
references: Ann Intern Med. 2000 Mar 7;132(5):345-53
references: 10691584
references: Am J Clin Nutr. 1986 Feb;43(2):299-305
references: 3946294
references: J Bone Miner Res. 2012 Oct;27(10):2097-107
references: 22589201
references: Osteoporos Int. 2002 Jan;13(1):83-8
references: 11883410
references: J Nutr. 2003 Feb;133(2):374-80
references: 12566470
references: Am J Clin Nutr. 2000 Aug;72(2):466-71
references: 10919942
references: Nat Rev Genet. 2012 Jul 18;13(8):576-88
references: 22805710
references: J Bone Miner Res. 2010 Aug;25(8):1842-9
references: 20205166
references: Am J Physiol. 1986 May;250(5 Pt 1):G561-9
references: 2939728
references: J Bone Miner Res. 1995 Mar;10(3):384-93
references: 7785459
references: J Bone Miner Res. 2008 Mar;23(3):392-9
references: 17997712
references: Am J Clin Nutr. 1996 Jan;63(1):72-9
references: 8604673
references: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13324-9
references: 11687634
references: Bone. 1999 Oct;25(4):413-20
references: 10511107
references: J Clin Endocrinol Metab. 1985 Apr;60(4):651-7
references: 3156144
references: Eur J Endocrinol. 2004 Dec;151(6):759-63
references: 15588243
references: Calcif Tissue Int. 2005 Nov;77(5):281-90
references: 16283571
references: Am J Clin Nutr. 1990 Nov;52(5):878-88
references: 2239765
references: J Bone Miner Res. 2010 Jul;25(7):1468-86
references: 20533309
references: J Am Diet Assoc. 2003 Oct;103(10):1320-5
references: 14520251
references: Nutr Rev. 2011 Jul;69(7):347-70
references: 21729089
references: Osteoporos Int. 2012 Nov;23(11):2607-14
references: 22282301
references: Can J Physiol Pharmacol. 1996 Aug;74(8):911-7
references: 8960380
references: J Am Soc Nephrol. 2006 Nov;17(11):3020-7
references: 17005931
references: Osteoporos Int. 1997;7(2):105-12
references: 9166389
references: J Bone Miner Res. 2001 Apr;16(4):615-24
references: 11315989
references: Am J Clin Nutr. 1990 Feb;51(2):290-300
references: 2407100
references: J Bone Miner Res. 2011 Sep;26(9):2174-83
references: 21638317
references: J Bone Miner Res. 1997 Jun;12(6):922-8
references: 9169351
references: J Clin Endocrinol Metab. 2008 Oct;93(10):3907-14
references: 18682505
references: Mol Biol Cell. 2008 May;19(5):1912-21
references: 18287530