Can High-Protein Diets Help You Lose Weight? (FTO)

FTO is one of the best-studied genes when it comes to body weight and obesity, hence the name: fat mass and obesity-associated gene. It’s the first discovered genetic link to obesity and continues to be the gene with the largest known effect on body weight to this day [R, R, R].

An SNP in this gene, rs9939609, has shown a robust association with obesity across different ages and ethnic groups. Carriers of the minor 'A' allele tend to gain more weight and have higher rates of obesity [R, R, R, R].

Luckily for people with this and other problematic FTO variants, different environmental and genetic factors can lessen their negative metabolic impact. In this post, we will explore how protein content and other dietary factors modify the link between this gene, obesity, and metabolic health [R, R, R].

FTO was the first gene linked to obesity. Robust evidence suggests that the 'A' allele at rs9939609 is associated with increased body weight and higher rates of obesity.

How It Works

A lot is still unclear about FTO functions, but studies suggest this gene works as a “master switch” that controls a variety of other weight-associated genes and pathways in our bodies [R, R].

One of the primary ways that FTO may affect body weight is through its influence on appetite, emotional aspects of eating, and food preferences. Another potential mechanism includes its adverse effects on fat metabolism and energy expenditure [R, R, R]. 

Rs9939609-A and Food Perception

Many human studies suggest that the 'A' allele at rs9939609 is associated with:

• Higher levels of ghrelin or the "hunger hormone" [R]
• Higher food intake [R, R, R]
• Increased preference for higher-calorie foods [R, R, R]
• Increased enjoyment of food [R]
• Not feeling full after meals [R, R, R]
• Eating in the absence of hunger [R, R]
• Food cravings [R]
• Emotional and binge eating [R]

It's also important to note that, while the studies mentioned above are promising, the exact mechanisms by which FTO affects weight are still not entirely clear.

Many of these studies rely on subjective diet reports from the participants, which are not always reliable measurements. Additionally, some studies have failed to find a link between food intake and this SNP, while others offer alternative explanations for its mode of action [R, R, R].

We'll keep you updated with the latest findings as scientists keep learning more about this complex gene and its effects on metabolism and food intake.

FTO variants such as rs9939609 may increase appetite, emotional eating, and craving for high-calorie foods. However, the exact mechanisms behind their link with obesity are yet to be discovered.

Rs9939609 and Metabolic Health

In addition to its potential influence on appetite and hunger control, this SNP may also affect our metabolism. For example, several studies suggest that the 'A' allele of rs9939609 may be linked with higher insulin resistance and diabetes rates [R, R, R, R].

Other studies confirmed this link in some populations, but not others. Hence, it's still too early to conclude the exact role of this SNP in metabolic health [R].

The impact of different dietary interventions on the link between FTO variants and obesity has been a hot topic for over a decade. The results don't allow for definite conclusions, but they point to the interesting effects of dietary protein intake.

In a study of 737 overweight adults, higher protein intake (25% of total calories) reduced appetite and food cravings in people with rs9939609-A, despite the calorie restriction [R].

Another FTO variant, rs1558902, showed a significant interaction with dietary protein among those participants. The “A” allele carriers following a high-protein diet lost significantly more fat mass, compared with the “TT” genotype. On the other hand, a low-protein diet suited the “T” carriers better [R].

After six months on the assigned diet, people partly regained their weight, which lessened the protective effects of dietary protein [R].

A trial of nearly 1,500 participants came to a similar conclusion for rs1558902:

Carriers of the "AA" genotype with low protein intake (≤ 18% total energy) had higher body mass index (BMI) and waist circumference. There was no difference between genotypes among those who consumed more protein. However, the effect was significant only among East Asian participants (e.g., China, Japan) [R].

According to some studies, higher protein intake may lessen the impact of FTO variants, such as rs9939609-A and rs1558902-A, on obesity.

Limitations

Unlike the above papers, a comprehensive meta-analysis of 40 studies and over 170,000 participants failed to confirm the impact of dietary factors, including protein intake, on the link between FTO and obesity [R].

In a smaller trial of 195 patients, a high-protein diet helped reduce weight and improve metabolic parameters such as [R]:

• Total cholesterol
• Triglycerides
• LDL
• Insulin resistance

It appeared to be a better solution compared with a standard low-calorie diet but worked equally well across all rs9939609 genotypes [R].

Interestingly, a large meta-analysis including over 16,000 children and adolescents observed the opposite: the link between FTO variants and BMI was stronger in those who consumed more protein. Further analysis of different populations confirmed this finding only in whites [R].

Further research will hopefully shed more light on the link between FTO, dietary protein, and obesity. Keep reading for a potential explanation of these contradictory findings…

Many studies have questioned the interaction between FTO variants and protein intake, and some even observed the negative impact of high-protein diets in children and adults. Further research is warranted.

Potential Mechanisms

The exact mechanisms by which dietary protein affects the FTO gene and its metabolic effects are not fully clear. Researchers suggest appetite control as a possible answer, given the well-known roles of FTO in food cravings and appetite [R, R].

Indeed, dietary protein improves satiety and thus makes a valuable part of weight control [R, R].

Scientists have discovered that amino acids (protein building blocks) can drastically reduce FTO gene expression, which may help suppress high-calorie food cravings [R].

However, increased protein intake was beneficial regardless of the total calorie intake, suggesting that some other mechanisms might be at play, too.

Increased protein intake may reduce food cravings by suppressing FTO, but we still don’t know the exact mechanisms at play.

SNP Summary and Table

Primary SNPs:

FTO rs9939609

• “T” – not associated with a response to high-protein diets
• “A” – associated with a reduced appetite and food cravings on a high-protein diet

Population frequency: around 64% of European, 30% of East Asian, and 75% of African descendants carry at least one copy of the “A” allele

FTO rs1558902

• “T” – associated with a higher BMI and fat mass on a high-protein diet
• “A” – associated with a lower BMI and fat mass on a high-protein diet

Population frequency: around 64% of European, 30% of East Asian, and 11% of African descendants carry at least one copy of the “A” allele.

With the exception of African populations, these two variants are almost always inherited together, so they act as a single genetic factor.