Changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing an intensive lifestyle intervention and the role of FTO genotype in this interaction

Abstract

Background: Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of FTO genotype in this interaction.

Methods: This study was a field trial of 62 adolescents from boys' high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in peripheral blood mononuclear cells (PBMCs). Anthropometric measurements were assessed at baseline and after 18 weeks of intensive lifestyle intervention.

Results: Our results showed that IRX3 expression in the intervention group was significantly up-regulated compared to baseline (P = 0.007) and compared to the control group (P = 0.011).The intervention group had significantly up-regulated transcripts of IRX3 only in rs9930506 risk allele carriers of the intervention group compared to risk allele carriers of the control group (P = 0.017). Moreover, our data showed that the FTO expression was up-regulated in AA genotype carriers and down-regulated in AG/GG genotype carriers (P = 0.017).

Conclusion: Lifestyle modification may exert its effects on obesity through changes in the expression level of the FTO and IRX3 genes. However, FTO genotype plays a role in the extent of the effect of lifestyle changes on gene expression. Further studies are crucial to have a better understanding of the interaction between lifestyle, genetics and anthropometric measurements. Trial registration This paper reports a comprehensive intervention study (Interactions of Genetics, Lifestyle and Anthropometrics study or IGLA study), which is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( https://www.irct.ir/searchresult.php?id=25699&number=2 ).

Keywords: FTO; Gene expression; Genotype; IRX3; Obesity.

Fig. 1

Gene expression of IRX3 and FTO in blood samples of the intervention and control groups after 18 weeks. The fold change represents the ratio of the expression of the gene at the end of study to its expression at baseline. Data are presented as mean ± S.E.M. P-value was calculated using a two-tailed distribution independent t-test. *P < 0.05. As you note, gray is used for the graphs of the intervention group and black is used for the graphs of the control group

Fig. 2

BMI-associated SNP is associated with expression of FTO, but not IRX3, in PBMCs. Gray is used for the graphs of the subjects with AG/GG genotype of rs9930506 and black is used for the graphs of the subjects with AA genotype. The allele of rs9930506 associated with increased BMI (risk allele) is correlated with decreased FTO expression and not with IRX3 expression

Fig. 3

The role of FTO genotype on IRX3 and FTO expression. Gray is used for the graphs of the subjects with AG/GG genotype of rs9930506 and black is used for the graphs of the subjects with AA genotype. FTO expression was up-regulated in AA carriers and down-regulated in G allele carriers in the intervention group

Fig. 4

The effect of intervention genotype categories. Gray is used for the graphs of the intervention group and black is used for the graphs of the control group. In risk allele carriers, IRX3 expression was unchanged in the control group and up-regulated in the intervention group (P = 0.017)