PPARG by Dietary Fat Interaction Influences Bone Mass in Mice and Humans

Overview

Journal J Bone Miner Res

Publisher Oxford University Press

Date 2008 Aug 19

PMID 18707223

Citations 37

Authors

Cheryl L Ackert-Bicknell

Serkalem Demissie

Caralina Marin de Evsikova

Yi-Hsiang Hsu

Victoria E DeMambro

David Karasik

L Adrienne Cupples

Jose M Ordovas

Katherine L Tucker

Kelly Cho

Ernesto Canalis

Beverly Paigen

Gary A Churchill

Jiri Forejt

Wesley G Beamer

Serge Ferrari

Mary L Bouxsein

Douglas P Kiel

Clifford J Rosen

Affiliations

Soon will be listed here.

Abstract

Adult BMD, an important risk factor for fracture, is the result of genetic and environmental interactions. A quantitative trait locus (QTL) for the phenotype of volumetric BMD (vBMD), named Bmd8, was found on mid-distal chromosome (Chr) 6 in mice. This region is homologous to human Chr 3p25. The B6.C3H-6T (6T) congenic mouse was previously created to study this QTL. Using block haplotyping of the 6T congenic region, expression analysis in the mouse, and examination of nonsynonymous SNPs, peroxisome proliferator activated receptor gamma (Pparg) was determined to be the most likely candidate gene for the Bmd8 QTL of the 630 genes located in the congenic region. Furthermore, in the C3H/HeJ (C3H) strain, which is the donor strain for the 6T congenic, several polymorphisms were found in the Pparg gene. On challenge with a high-fat diet, we found that the 6T mouse has a lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the distal femur compared with B6 mice. Interactions between SNPs in the PPARG gene and dietary fat for the phenotype of BMD were examined in the Framingham Offspring Cohort. This analysis showed that there was a similar interaction of the PPARG gene and diet (fat intake) on aBMD in both men and women. These findings suggest that dietary fat has a significant influence on BMD that is dependent on the alleles present for the PPARG gene.

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References

Bouxsein M, Rosen C, Turner C, Ackert C, Shultz K, Donahue L . Generation of a new congenic mouse strain to test the relationships among serum insulin-like growth factor I, bone mineral density, and skeletal morphology in vivo. J Bone Miner Res. 2002; 17(4):570-9. DOI: 10.1359/jbmr.2002.17.4.570. View

Lee Y, Rho Y, Choi S, Ji J, Song G . Meta-analysis of genome-wide linkage studies for bone mineral density. J Hum Genet. 2006; 51(5):480-486. DOI: 10.1007/s10038-006-0390-9. View

Griffiths M, Remmers E . Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease loci. Immunol Rev. 2002; 184:172-83. DOI: 10.1034/j.1600-065x.2001.1840116.x. View

Ioannidis J, Ng M, Sham P, Zintzaras E, Lewis C, Deng H . Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J Bone Miner Res. 2007; 22(2):173-183. PMC: 4016811. DOI: 10.1359/jbmr.060806. View

Williams F, Spector T . Recent advances in the genetics of osteoporosis. J Musculoskelet Neuronal Interact. 2006; 6(1):27-35. View

Abiola O, Angel J, Avner P, Bachmanov A, Belknap J, Bennett B . The nature and identification of quantitative trait loci: a community's view. Nat Rev Genet. 2003; 4(11):911-6. PMC: 2063446. DOI: 10.1038/nrg1206. View

Ralston S, de Crombrugghe B . Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev. 2006; 20(18):2492-506. DOI: 10.1101/gad.1449506. View

Abdelmagid S, Barbe M, Arango-Hisijara I, Owen T, Popoff S, Safadi F . Osteoactivin acts as downstream mediator of BMP-2 effects on osteoblast function. J Cell Physiol. 2006; 210(1):26-37. DOI: 10.1002/jcp.20841. View

Lecka-Czernik B, Suva L . Resolving the Two "Bony" Faces of PPAR-gamma. PPAR Res. 2007; 2006:27489. PMC: 1679961. DOI: 10.1155/PPAR/2006/27489. View

10.

Lazarenko O, Rzonca S, Hogue W, Swain F, Suva L, Lecka-Czernik B . Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology. 2007; 148(6):2669-80. PMC: 2084459. DOI: 10.1210/en.2006-1587. View

11.

Kuhn H, Anton M, Gerth C, Habenicht A . Amino acid differences in the deduced 5-lipoxygenase sequence of CAST atherosclerosis-resistance mice confer impaired activity when introduced into the human ortholog. Arterioscler Thromb Vasc Biol. 2003; 23(6):1072-6. DOI: 10.1161/01.ATV.0000074167.01184.48. View

12.

Deng H, Xu F, Huang Q, Shen H, Deng H, Conway T . A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait Loci for osteoporosis. J Clin Endocrinol Metab. 2002; 87(11):5151-9. DOI: 10.1210/jc.2002-020474. View

13.

Park Y, Clifford R, Buetow K, Hunter K . Multiple cross and inbred strain haplotype mapping of complex-trait candidate genes. Genome Res. 2003; 13(1):118-21. PMC: 430946. DOI: 10.1101/gr.786403. View

14.

Gao Y, Kobayashi H, Ganss B . The human KROX-26/ZNF22 gene is expressed at sites of tooth formation and maps to the locus for permanent tooth agenesis (He-Zhao deficiency). J Dent Res. 2003; 82(12):1002-7. DOI: 10.1177/154405910308201213. View

15.

de Haan G, Bystrykh L, Weersing E, Dontje B, Geiger H, Ivanova N . A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover. Blood. 2002; 100(6):2056-62. DOI: 10.1182/blood-2002-03-0808. View

16.

Karasik D, Myers R, Cupples L, Hannan M, Gagnon D, Herbert A . Genome screen for quantitative trait loci contributing to normal variation in bone mineral density: the Framingham Study. J Bone Miner Res. 2002; 17(9):1718-27. DOI: 10.1359/jbmr.2002.17.9.1718. View

17.

Garland M, Sacks F, Colditz G, Rimm E, Sampson L, Willett W . The relation between dietary intake and adipose tissue composition of selected fatty acids in US women. Am J Clin Nutr. 1998; 67(1):25-30. DOI: 10.1093/ajcn/67.1.25. View

18.

Ogawa S, Urano T, Hosoi T, Miyao M, Hoshino S, Fujita M . Association of bone mineral density with a polymorphism of the peroxisome proliferator-activated receptor gamma gene: PPARgamma expression in osteoblasts. Biochem Biophys Res Commun. 1999; 260(1):122-6. DOI: 10.1006/bbrc.1999.0896. View

19.

Lyons M . Arachidonate 5-lipoxygenase variants in atherosclerosis, obesity, and bone traits. Circ Res. 2006; 98(8):e66. DOI: 10.1161/01.RES.0000219674.81938.63. View

20.

Beamer W, Shultz K, Donahue L, Churchill G, Sen S, Wergedal J . Quantitative trait loci for femoral and lumbar vertebral bone mineral density in C57BL/6J and C3H/HeJ inbred strains of mice. J Bone Miner Res. 2001; 16(7):1195-206. DOI: 10.1359/jbmr.2001.16.7.1195. View