Is Saturated Fat Hindering Your Weight Loss? (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].

The good news is that different environmental factors can modify the adverse metabolic impact of FTO variants. This post explores the links between FTO, dietary fat, obesity, and metabolic health [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]. 

Many clinical trials 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]

FTO variants such as rs9939609-A may increase appetite, emotional eating, and craving for high-calorie foods. 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 papers 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].

Many studies have investigated whether and how dietary fat impacts the link between FTO, metabolic health, and obesity. In this section, we will summarize the effects of dietary fat in general, as well as different types such as saturated fat.

Negative Response to High-Fat Diets

In a Swedish study of over 4,800 subjects, the link between rs9939609-A and obesity was restricted to people who practiced a high-fat diet. There was no difference between genotypes in people consuming a high-carb, low-fat diet [R].

Two more studies of 652 adolescents and 479 adults confirmed the above results. The more fat people consumed, the stronger impact this variant had on obesity. Reduced intake of complex carbs and fiber may be partly responsible for this phenomenon [R, R].

In a small study of 106 participants, those with rs9939609-A lost more weight on a low-fat hypocaloric diet, compared with the “TT” carriers. According to another trial, people with this variant on a low-fat diet may see a greater improvement in [R, R]:

• Total cholesterol
• LDL
• CRP (inflammation) 

According to the majority of clinical evidence, high-fat diets may worsen the negative metabolic impact of the FTO variant rs9939609-A. 

Positive Response to High-Fat Diets

A clinical trial of 743 obese adults observed a potential advantage of a high-fat diet in people with the “A” allele at rs1558902. Unlike low-fat, a high-fat diet lessened the negative effect of this variant on insulin resistance. However, the observed results may be due to reduced intake of carbs and sugars [R].

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 fat intake, on the link between FTO and obesity. We should wait for more research before jumping to conclusions [R].

Response to Different Types of Fat

An analysis of two studies and 2,150 total participants revealed an adverse effect of excess saturated fat (SF) on FTO-associated obesity. People with rs9939609-A and rs1121980-A had a significantly higher BMI (body-mass index) only in the presence of a high SF intake [R].

Scientists observed similar results in two studies of 1,750 adults and 350 children. Those with rs9939609-A were more prone to abdominal obesity only when they consumed more saturated fat (>15.5% and 12.5% of total calories, respectively). On the other hand, polyunsaturated fatty acids (PUFA) had a protective effect [R, R].

In a trial of 233 obese adults, a diet high in PUFA also improved metabolic health in people with this variant. Compared with a high-MUFA diet, it improved LDL, total cholesterol, and insulin resistance. Both diets were equally effective for weight loss [R].

Trans fats are notorious for their adverse metabolic effects. A comprehensive Iranian study of 4,300 subjects suggests they may be particularly harmful to people with FTO variants and worsen their abdominal obesity [R].

People with rs9939609-A and other FTO variants may benefit from reducing the intake of saturated and trans fats and consuming more polyunsaturated fatty acids.

Rs9939609-A and the Mediterranean diet

In over 7,000 subjects at high risk for heart disease, the Mediterranean diet lessened the metabolic burden of rs9939609-A. People with this variant had a higher risk of type 2 diabetes only when their adherence to the Mediterranean diet was low [R].

At the same time, this diet canceled out the link between FTO and obesity, but these two effects were independent of each other [R].

In a trial of 776 elderly on the Medirannean diet, those with the “A” allele at rs9939609 gained less weight than the “TT” carriers, even though they initially had a higher average BMI [R].

The Mediterranean diet may protect the heart and improve blood sugar control regardless of the genes, so it can be a healthy choice for anyone [R, R].

The Mediterranean diet can protect the heart, improve metabolic health, and support weight control. It may be particularly useful for people carrying the “A” allele at rs9939609.

Did you know? According to one study, people who are informed about their FTO genotypes show greater improvements in response to dietary and lifestyle interventions. Keep this in mind while reading the gene-based recommendations below [R].

SNP Summary and Table

Primary SNPs:

FTO rs9939609

• “T” – not associated with a response to high-fat diets or saturated fat
• “A” – associated with a poor metabolic response to high-fat diets and saturated fat

FTO rs1121980

• “G” – not associated with a response to saturated fat
• “A” – associated with a poor metabolic response to excess saturated fat

Population frequency

These two variants are almost always inherited together, especially in European populations. Around 65% of European, 35% of East Asian, and 73% of African descendants carry at least one copy of the minor “A” alleles.