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 ) Electronic supplementary material The online version of this article (10.1186/s12967-019-1921-4) contains supplementary material, which is available to authorized users.

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

“…Data are expressed as mean ± SEM of the fold change at 10 and 90 mins compared to pre-exercise measurements (set arbitrarily to 1). 'a' represents significant main effect for time (p < 0.05) FTO genotype was considered, FTO expression was upregulated in AA genotype carriers and down-regulated in AG/GG genotype carriers in the intervention group [29]. Though the direction of FTO mRNA change was opposite to the present study observations, different cell type, age, sex and intervention period, may explain such differences.…”

“…Previous studies have shown that FTO gene activity is nutritionally regulated with high fat diet, fasting and glucose ingestion all having effects on FTO mRNA levels [26][27][28]. Only one other study has investigated the effect of high intensity training on FTO mRNA expression and showed lifestyle changes (diet and exercise) did not impact FTO gene expression in peripheral blood mononuclear cells [29]. However, when Fig.…”

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

“…Previous studies have shown that FTO gene activity is nutritionally regulated with high fat diet, fasting and glucose ingestion all having effects on FTO mRNA levels [26][27][28]. Only one other study has investigated the effect of high intensity training on FTO mRNA expression and showed lifestyle changes (diet and exercise) did not impact FTO gene expression in peripheral blood mononuclear cells [29]. However, when FTO genotype was considered, FTO expression was up-regulated in AA genotype carriers and downregulated in AG/GG genotype carriers in the intervention group [29].…”

“…Only one other study has investigated the effect of high intensity training on FTO mRNA expression and showed lifestyle changes (diet and exercise) did not impact FTO gene expression in peripheral blood mononuclear cells [29]. However, when FTO genotype was considered, FTO expression was up-regulated in AA genotype carriers and downregulated in AG/GG genotype carriers in the intervention group [29]. Though the direction of FTO mRNA change was opposite to the present study observations, different cell type, age, sex and intervention period, may explain such differences.…”

Genes and Diet in the Prevention of Chronic Diseases in Future Generations

“…Recently, it has been suggested that lifestyle modifications, including personalized diet and physical activity intervention, may impact on obesity through changes in the expression level of the FTO and IRX3 genes. However, this effect is mediated by the genotype of FTO, which is capable of modulating the impact of lifestyle changes on its own expression [68]. These findings have highlighted how important gene variants related to nutrients and metabolism are, especially in terms of a possible link between dietary intake and gene expression and their related functions [69].…”