How the FTO gene increases the risk of obesity

Urmeli Katus
About the Author

Urmeli Joost is a PhD student at the Institute of Family Medicine and Public Health, University of Tartu, Estonia. Her main focus of research is the genetic, environmental and behavioural factors in obesity, dyslipidemia and glucose metabolism.

Did you know that in year 2015 more than 100 million children and 600 million adults had obesity? In fact, the prevalence of obesity has almost doubled since 1980 and it doesn’t seem to be slowing down (1). Factors like genetics, biology, individual behaviors such as diet and physical activity, and other influences from an individual’s environment and lifestyle, play a role in the development of obesity (2).

Developments in the field of genetics have given us the opportunity to search through an individual’s whole genetic material (called the genome) for small genetic variations that occur more frequently in people who have a particular disease or a trait. This has enabled us to find several genetic variations that are associated with obesity (3). One of those is the gene encoding fat mass and obesity associated protein (FTO), a protein that is a member of the alpha-ketoglutarate-dependent hydroxylases. While we know that FTO gene is associated with the development of obesity, the pathways are still under debate.

Several pathways have been suggested from increased energy intake, increased appetite, reduced satiety, loss of control over eating and modifying effect of physical activity (4), to the regulation in expression of neighboring genes IRX3 and IRX5 leading to a reduced energy expenditure (5). In our longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS) we found that men, with the risk allele (FTO rs1421085 C-allele), had higher body mass index, body fat percentage and hip circumference from the age 15 to 25 years. Findings were similar at age 9 years. In women, only waist-to-hip ratio was greater in subjects homozygous for the risk allele.

The effect of FTO rs1421085 risk allele on obesity risk was not influenced by daily energy intake, macronutrient intake or physical activity. However, amongst women we found an interaction between FTO and the socioeconomic status (6), indicating a relationship between the FTO gene and the environment.

In conclusion, the FTO gene increases the risk of developing obesity, but we don’t fully understand this mechanism yet. Our findings indicate that the weight increasing effect of FTO gene is not through energy intake. When analyzing the effect of the FTO gene on obesity, further research should consider the potential effect modifying impact of sex, age and socioeconomic environment (6).