The ECPBHS study specifies timing of the effect of transcription factor AP-2B on obesity and energy metabolism, and reveals gender differences

16. Jul 2019

The prevalence of overweight and obesity has increased worldwide and is affecting millions of adults and children (1). The development of obesity is complex with factors like genetics, individual metabolism, dietary and physical activity choices, food and water availability, education and culture, playing a role (2). Several genome wide association studies have revealed an association between obesity and the gene encoding the transcription factor AP-2 beta (TFAP2B) (3,4). But how does TFAP2B contribute to the development of obesity is not known.

We have now shown in our ECPBHS study a very clear association between one TFAP2B variation (intron 2 VNTR) and measures of obesity and insulin resistance. Our findings have just recently published in the International Journal of Obesity (5) and you can read about it more in our upcoming blog on New Brain Nutrition website.

We found that men, who inherited the same variant of that gene (5 repeat allele) from both parents, had significantly higher body weight, body mass index, proportion of body fat, insulin resistance, throughout adolescence to young adulthood. The genotype effect in females appeared later, in young adulthood.

We hypothesized that TFAP2B 5/5 homozygotes consumed more food. Surprisingly, by age 25 years’ male 5/5 homozygotes had smaller daily calorie intake and consumption of fats and carbohydrates.

In conclusion, the effect of TFAP2B on obesity, abdominal obesity and insulin resistance was large in this sample, and is probably related to differences in metabolism. We should consider implementing lifestyle interventions already in childhood to reduce the effect of TFAP2B on body weight. The physiological role of TFAP2B in body weight regulation and insulin resistance still needs further research.

References
1. GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med 2017; 377: 13–27. doi:10.1056/NEJMoa1614362
2. Lee BY, Bartsch SM, Mui Y, Haidari LA, Spiker ML, Gittelsohn J. A systems approach to obesity. Nutr Rev 2017; 75: 94–106. doi:10.1093/nutrit/nuw049
3. Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 2015; 518: 197–206. doi:10.1038/nature14177
4. Felix JF, Bradfield JP, Monnereau C, et al. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum Mol Genet 2016; 25: 389-403. doi:10.1093/hmg/ddv472
5. Joost U, Villa I, Comasco E, Oreland L, Veidebaum T, Harro J. Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study. Int J Obes 2019. doi:10.1038/s41366-019-0396-y