FTO (rs9939609): The Obesity Gene

FTO (Fat Mass and Obesity-Associated gene) was the first gene convincingly linked to common obesity through genome-wide association studies. The rs9939609 variant is among the most studied in obesity genetics, with each risk allele associated with ~3 kg higher body weight and 1.7x increased obesity risk. However, this genetic predisposition can be substantially modified by lifestyle factors.

Understanding FTO

FTO's role in obesity is complex and still being understood:

• Original name: Fat mass and obesity-associated
• Function: RNA demethylase (modifies RNA)
• Expression: Highest in brain, particularly hypothalamus
• Effect: Influences appetite, food intake, and possibly energy expenditure

The Mechanism

Research suggests FTO variants work through multiple pathways:

• May affect nearby IRX3/IRX5 genes that influence fat cell development
• Influences ghrelin (hunger hormone) signaling
• Affects hypothalamic appetite circuits
• May influence fat cell type (white vs. beige)

The rs9939609 Variant

• T allele: Lower risk allele
• A allele: Risk allele - associated with higher BMI

Understanding Your Genotype

• T/T: Lower genetic obesity risk (~16% of Europeans)
• T/A: Intermediate risk - ~1.3x obesity risk
• A/A: Higher risk - ~1.7x obesity risk, ~3 kg heavier on average

Effects on Eating Behavior

Increased Hunger

• A allele carriers report higher levels of hunger
• Reduced satiety after meals
• Higher levels of circulating ghrelin (hunger hormone)

Food Preferences

• Preference for energy-dense, high-fat foods
• May consume more calories at meals
• Snacking behavior often increased
• Loss of control eating more common

Satiety Signaling

• Brain response to food cues altered
• Less sensitive to fullness signals
• May continue eating past satiety point

The Good News: Lifestyle Modification Works

Physical Activity

Multiple studies show physical activity substantially reduces FTO's effect:

• Active A/A carriers have similar BMI to inactive T/T carriers
• Effect of FTO reduced by ~30% in physically active individuals
• Both structured exercise and active lifestyle help
• This is one of the most modifiable obesity genes

Exercise Recommendations

• Minimum: 150 minutes moderate activity weekly
• Better: 300+ minutes for weight management
• Include: Both cardio and resistance training
• Non-exercise activity: Walking, standing, taking stairs also counts

Diet Response

• FTO carriers can lose weight with caloric restriction
• Response to weight loss interventions is similar across genotypes
• High-protein diets may be particularly beneficial
• Weight loss is possible - it may just require more vigilance

Dietary Strategies

Protein Priority

• High-protein diets associated with better outcomes in FTO risk allele carriers
• Protein is most satiating macronutrient
• Aim for protein at each meal
• May help counteract reduced satiety

Fiber and Volume

• High-fiber foods increase fullness
• Vegetables, fruits, whole grains
• Low energy density - more food for fewer calories

Fat Quality

• Some evidence that saturated fat has stronger effect in A/A carriers
• Mediterranean-style diet may be beneficial
• Emphasize olive oil, nuts, fatty fish over saturated fats

Meal Patterns

• Regular meals to prevent excessive hunger
• Avoid skipping meals (leads to overeating later)
• Mindful eating to recognize satiety cues

Behavioral Approaches

Environment Design

• Keep high-calorie foods out of sight/home
• Smaller plates and portions
• Pre-portion snacks
• Make healthy choices the easy choices

Awareness Strategies

• Food tracking can help - FTO carriers may underestimate intake
• Mindful eating practice
• Recognize emotional vs. physical hunger
• Plan meals and snacks in advance

FTO and Weight Regain

Maintenance Challenges

• FTO risk allele associated with weight regain after loss
• Persistent appetite effects make maintenance harder
• Long-term vigilance needed

Successful Maintenance

• Continued physical activity is crucial
• Self-monitoring (weighing, food tracking) helps
• Support systems beneficial
• Recognize that maintenance requires ongoing effort

Children and FTO

Early Effects

• FTO effects visible from childhood
• A/A children tend to have higher BMI
• Eating behaviors differ early
• Early healthy habits especially important

Family Strategies

• Model healthy eating
• Active family lifestyle
• Limit screen time
• Avoid restrictive dieting (can backfire)
• Focus on health, not weight

Prevalence

• A allele frequency: ~40-45% in Europeans
• A/A genotype: ~16-20%
• Population variation: Lower in East Asians (~15% A allele)
• Note: Very common - many people carry risk alleles

Testing with NutraHacker

NutraHacker's Fitness Report analyzes FTO along with MC4R and other weight-related variants, providing a comprehensive view of your genetic influences on weight.

Frequently Asked Questions

Is FTO really the "obesity gene"?

FTO was the first common obesity-associated gene discovered and has the largest effect of common variants, but it's not destiny. Having A/A increases obesity risk ~1.7-fold and accounts for about 3 kg of weight - significant but not overwhelming. Hundreds of genes influence weight, and lifestyle factors remain dominant. Think of FTO as one piece of a complex puzzle.

Can I overcome my FTO genetics with exercise?

Yes! This is one of the best-documented gene-lifestyle interactions. Studies consistently show that physical activity substantially reduces FTO's effect on BMI. Active A/A carriers can achieve similar weights to inactive T/T carriers. This makes exercise particularly important if you carry FTO risk alleles.

Why do I struggle more with weight than my friends who eat the same?

FTO affects hunger and satiety signals, so you may genuinely feel more hungry and less satisfied than friends with different genetics eating the same meal. You're not imagining it. Understanding this can help you adopt specific strategies (more protein, more fiber, mindful eating, physical activity) rather than just trying to eat like someone with different genetics.

References

1. Frayling TM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889-894.
2. Kilpeläinen TO, et al. Physical activity attenuates the influence of FTO variants on obesity risk. Am J Clin Nutr. 2011;93(3):596-604.
3. Loos RJ, Yeo GS. The bigger picture of FTO: the first GWAS-identified obesity gene. Nat Rev Endocrinol. 2014;10(1):51-61.