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

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.

SUBMITTER: Ackert-Bicknell CL

PROVIDER: S-EPMC2683155 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Ackert-Bicknell Cheryl L CL Demissie Serkalem S Marín de Evsikova Caralina C Hsu Yi-Hsiang YH DeMambro Victoria E VE Karasik David D Cupples L Adrienne LA Ordovas Jose M JM Tucker Katherine L KL Cho Kelly K Canalis Ernesto E Paigen Beverly B Churchill Gary A GA Forejt Jiri J Beamer Wesley G WG Ferrari Serge S Bouxsein Mary L ML Kiel Douglas P DP Rosen Clifford J CJ

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20080901 9

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, peroxis ...[more]

PMID: 18707223

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Project description:A single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is a strong predictor of obesity in humans. The FTO SNP (rs1421085) results in a T to C nucleotide substitution that may result in an increased risk for obesity in individuals who carry at least one C allele. The purpose of this investigation was to characterize the FTO genotype in a cohort of exercise-trained men and women.We tested 108 exercise-trained individuals that included professional mixed martial arts fighters, competitive distance runners, collegiate swimmers, stand-up paddlers as well as a cohort of recreational bodybuilders. Body composition was assessed via dual-energy x-ray absorptiometry (DXA). Saliva samples were collected in order to genotype participants and quantify cortisol levels.The physical characteristics of the subjects were as follows (mean±SD): body weight 74.5±15.6 kg; height 171.5±9.5 cm; bone mineral content 2.8±0.7 kg; fat mass 15.7±5.5 kg; lean body mass 55.9±14.4 kg; % body fat 21.6±7.0. Independent samples t tests showed that C allele carriers (n =?54) had significantly higher fat mass t(106)?=?3.13, p <?0.01 and body fat percentage t(106)?=?2.68, p?<?0.01, relative to the TT group (n?=?54) (i.e., fat mass: C/-?17.3 ±5.6 kg, TT 14.2±4.6 kg; body fat percentage: C/- group 23.4±7.4%, TT group 19.9±6.2). No other measures of body composition were associated with the FTO genotype (i.e., body mineral density, bone mineral content, or lean body mass). Moreover, cortisol levels were significantly higher in the TT group relative to the C allele carriers t(106)?=?2.37, p =?0.02 (i.e., TT 0.35 ±0.35 ?g/dL, C/-?0.22±0.16 ?g/dL).Our findings demonstrate a relationship between C allele carriers on the FTO gene and a predisposition to a higher fat mass and body fat percentage. In addition, we found no relationship between cortisol and fat mass. However, due to the cross-sectional nature of this investigation, we cannot infer causality regarding the FTO gene and body composition.

Project description:Nutrigenetics studies the role of genetic variation on interactions between diet and health, aiming to provide more personalized dietary advice. However, replication has been low. Our aim was to study interaction among a functional APOA2 polymorphism, food intake, and body mass index (BMI) in independent populations to replicate findings and to increase their evidence level.Cross-sectional, follow-up (20 years), and case-control analyses were undertaken in 3 independent populations. We analyzed gene-diet interactions between the APOA2 -265T>C polymorphism and saturated fat intake on BMI and obesity in 3462 individuals from 3 populations in the United States: the Framingham Offspring Study (1454 whites), the Genetics of Lipid Lowering Drugs and Diet Network Study (1078 whites), and Boston-Puerto Rican Centers on Population Health and Health Disparities Study (930 Hispanics of Caribbean origin).Prevalence of the CC genotype in study participants ranged from 10.5% to 16.2%. We identified statistically significant interactions between the APOA2 -265T>C and saturated fat regarding BMI in all 3 populations. Thus, the magnitude of the difference in BMI between the individuals with the CC and TT+TC genotypes differed by saturated fat. A mean increase in BMI of 6.2% (range, 4.3%-7.9%; P = .01) was observed between genotypes with high- (> or =22 g/d) but not with low- saturated fat intake in all studies. Likewise, the CC genotype was significantly associated with higher obesity prevalence in all populations only in the high-saturated fat stratum. Meta-analysis estimations of obesity for individuals with the CC genotype compared with the TT+TC genotype were an odds ratio of 1.84 (95% confidence interval, 1.38-2.47; P < .001) in the high-saturated fat stratum, but no association was detected in the low-saturated fat stratum (odds ratio, 0.81; 95% confidence interval, 0.59-1.11; P = .18).For the first time to our knowledge, a gene-diet interaction influencing BMI and obesity has been strongly and consistently replicated in 3 independent populations.

Dataset Information

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

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

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