Appetite regulation

Protein intake and satiety

Constantly feeling hungry? Adjust your daily protein intake according to your genetics.

A variant form of the FTO gene is heavily linked with elevated sense of hunger and obesity. However, daily amount of protein intake attenuates this genetic predisposition.

 

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Gene: FTO (FAT MASS- AND OBESITY-ASSOCIATED GENE)
Genomic coordinates (GRCh38): 16:53,703,962-54,114,466

The FTO gene expresses in the hypothalamus region of the brain, controlling feeding and energy expenditure. The roll of FTO variants in regulation of appetite and satiety is well established. 

 

Recent meta-analysis studies which test these FTO variants include a total of close to half a million subjects, making it one of the most studied genetic polymorphisms ever.
The findings are clear: each A allele increases BMI, with an additional 1.7-fold increased risk for obesity.

 
FTO variant was found associated with ghrelin levels. Ghrelin is a hormone secreted by the gastrointestinal tract when the stomach is empty, and received in the hypothalamus as a cue for hunger. It was found that homozygous individuals exhibited increased ghrelin abundance (Figure C.) as well as smaller reduction in Ghrelin levels after meal (Figure D.). This means an elevated sense of hunger (Figure B.), and a decreased satiety after meal.

Karra, E. et al. (2013) ‘A link between FTO, ghrelin, and impaired brain food-cue responsivity’, The Journal of Clinical Investigation. American Society for Clinical Investigation, 123(8), pp. 3539–3551. doi: 10.1172/JCI44403.

However, individuals with the homozygous AA genotype should not despair.
Major studies have found a gene-diet  interaction with protein intake. It was found that high protein diet attenuates the effect of the genotype on BMI and fats. The following figure by Zhang showing loss of fat tissue in more than 800 individuals, over a 2-year diet intervention study.  

Zhang X, Qi Q, Zhang C, et al. FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial. Diabetes. 2012;61(11):3005-11.

These Scientists found that homozygotes for the risk allele had a greater reduction in weight in response to a high-protein diet, whereas an opposite genetic effect was observed in response to a low-protein diet. On the other hand, TT individuals lose more weight when on low-protein diet.

This is an amazing example of how your genotype interacts with your environment, with your choices, and in this case- with your diet. 

Here is another study showing that AA benefits a reduction in food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet.

Huang, Tao et al. 2014. “FTO Genotype, Dietary Protein, and Change in Appetite: The Preventing Overweight Using Novel Dietary Strategies Trial.” The American Journal of Clinical Nutrition 99(5):1126–30

Physical activity (PA) was also found to have big impact on the tendency for obesity in AA individuals. These findings were significant across ethnicities and various age groups, as shown by this figure:

 

Kilpeläinen, T. O. et al. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children. PLoS Med. 8, e1001116 (2011).

 

This study found that among AA genotype individuals, the risk of obesity is attenuated by 27% when physically active. Subjects were defined “active” if they performed  at least 1 h of moderate to vigorous leisure-time  physical activity per week. The FTO risk effect promoting obesity was totally diminished among people who were moderately exercising for 60 minutes daily.

Homozygotes for this gene set-up (carriers of two variant copies) are advised to consider adopting a protein-rich diet, with proteins accounting for 25%-30% of total calorie intake (125-150 grams of protein). Some high protein foods include lean meat, fish, shellfish, eggs, low-fat dairy products, legumes, tofu and seitan. Over-weight and obese should also adopt hypocaloric diet and practice satiety promoting eating behaviours. Physical activity should be practiced, as noted above.

Individuals carry no variant at all are the majority in the population (aka 'wild type' individuals). These individuals are advised to adopt a low protein diet (about 15% of total calorie intake) in order to lose weight, with a daily intake of up to 75 grams of protein. Some low-protein foods are whole grains, vegetables and fruits, "good" fats such as nuts and seeds, avocado, tahini and olive oil.