PPARG by dietary fat interaction influences bone mass in mice and humans

Cheryl L. Ackert-Bicknell, Serkalem Demissie, Caralina Marín 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

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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 γ (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.

Original languageEnglish
Pages (from-to)1398-1408
Number of pages11
JournalJournal of Bone and Mineral Research
Issue number9
StatePublished - Sep 2008
Externally publishedYes


  • Animal models
  • Candidate gene
  • Environmental interaction
  • Human population
  • Skeletal genetics


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