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TCF7L2

How Do Your Genes Respond to Dietary Fat? (TCF7L2)

Written by Aleksa Ristic, MS (Pharmacy) on March 10th, 2020

The TCF7L2 gene has crucial roles in sugar and fat metabolism. Variants in this gene may determine how well you respond to different dietary fats — read on to get gene-based diet tips for improved metabolic health.

TCF7L2 in Metabolic Health

The TCF7L2 (transcription factor 7 like 2) gene, previously known as TCF4, codes for a vital transcription factor. It controls the expression of other genes in digestive organs such as the gut and pancreas, with a particular role in glucose metabolism and insulin secretion [R, R].

TCF7L2 research has mostly focused on its strong association with type 2 diabetes. However, variants in this gene—such as rs7903146—also correlate with impaired lipid metabolism and heart disease [R, R, R, R].

The good news is that specific dietary approaches discussed in this post may lessen the negative metabolic impact of this gene.

How Does TCF7L2 Affect Fat Metabolism?

Besides its crucial role in glucose control, TCF7L2 is involved in fat metabolism. It regulates the production of signaling proteins—such as leptin and adiponectin—for weight gain, appetite, and more. The exact mechanisms behind this control are still unknown [R, R].

Complex metabolic roles of this gene have inspired scientists to investigate the impact of different nutrients on ‘problematic’ variants. In this post, we’ll focus on the response to dietary fat.

The Impact of Dietary Fat on TCF7L2 Variants

Total and Saturated Fat

In two studies of 4,000 participants, tailored nutritional and lifestyle interventions were able to lower or even remove the negative impact of TCF7L2 variants, rs12255372-T and rs7903146-T, on diabetes risk. Patients were educated and motivated to reduce weight, exercise more, and improve their diets [R, R].

Patients reduced the intake of total and saturated fat while increasing the consumption of fruits and vegetables. Besides fat reduction, other dietary and lifestyle changes likely had beneficial effects.

In two studies of 1,350 obese patients, those with the “TT” genotypes at rs7903146 and rs12255372 lost more weight on a low-fat (LF) than on a high-fat (HF) diet. They also had a lower waist-to-hip ratio and better glucose control. On the other hand, there was no significant difference between LF and HF among the “C” and “G” allele carriers [R, R].

High intake of saturated fat (≥15.5% of total energy) worsened the metabolic impact of rs7903146 in a trial of 1,754 subjects. The “T” allele carriers had 2.35x higher rates of metabolic syndrome, manifested with abdominal obesity and insulin resistance [R].

The effect was significant only in women, so ladies with this variant may want to pay special attention to their saturated fat intake.

In another study, the consumption of total and saturated fat-rich meals caused metabolic impairments in people with rs7903146-T. Young men had reduced HDL or “good” cholesterol, while the elderly had higher total cholesterol, LDL, and triglycerides [R].

Increased fat intake, especially saturated fat, may worsen the adverse metabolic effects of TCF7L2 variants: rs12255372-T and rs7903146-T.

Omega-6 Fatty Acids

Researchers examined the link between polyunsaturated fatty acids (PUFA) intake and TCF7L2 variants in a study of over 1,000 people. At high PUFA intake (>7% of total energy), those with rs7903146-T had impaired blood lipids and insulin secretion, which might contribute to diabetes and heart disease [R].

More precisely, a higher intake of omega-6 fatty acids had negative metabolic effects. Omega-3s were beneficial, regardless of the genotype.

Your TCF7L2 Results for Response to Dietary Fat

SNP Table

variant	genotype	frequency	risk allele
rs7903146
rs12255372

SNP Summary and Table

Primary SNP:

TCF7L2 rs7903146

‘C’ = typical response to dietary fat
‘T’ = poor response to high-fat diets, especially saturated and omega-6 fats

Other Important SNP:

TCF7L2 rs12255372

‘G’ = typical response to dietary fat
‘T’ = poor response to high-fat diets

Population Frequency

These two variants are almost always inherited together, which means they act as a single genetic factor.

About 40% of European descendants carry one copy of the problematic “T” allele while 10-12% carry both copies. In East-Asian populations, this allele is much less common (2-4%).

Recommendations

Diet

People with the mentioned TCF7L2 variations may want to limit the intake of saturated fat and omega-6 fatty acids.

Limit Saturated Fat

Foods high in saturated fat include [R, R]:

Fatty meat
High-fat dairy (cheese, cream)
Butter
Palm oil
Coconut oil
Pork fat
Lard

It’s worth mentioning that saturated fat has been unfairly “demonized” in the past. More recent evidence points to much lower health risks than initially reported [R, R, R].

It’s still a good idea to keep the saturated fat intake in moderation, especially for people with TCF7L2 variants.

Limit Omega-6 Fatty Acids

Foods high in omega-6 fatty acids include [R]:

Cakes and pastry
Fast food and snacks
Peanut butter
Vegetable oils (safflower, sunflower, sesame, soybean)

Western diets are too high in omega-6 and low in omega-3 fats. This impaired ratio can contribute to a range of inflammatory disorders [R, R, R].

Not all omega-6 sources are equal; they are present in many healthy foods such as eggs, nuts, and seeds. Make a special effort to avoid omega-6s from fried and fast foods, pastries, and sweets.

Healthy Replacements

Although some studies point to the harmful effects of total fat, they likely come from saturated, trans, and omega-6 fats. Try to replace the above foods with:

Fish (salmon, trout, sardine, herring)
Olive oil
Flaxseed
Hemp seeds
Walnuts
Chia seeds

Omega-3 sources and olive oil have well-documented anti-inflammatory effects and metabolic benefits, crucial for people with TCF7L2 variants [R, R, R, R].

These foods still add to total fat intake, so you should consume them moderately.

And what about carbs? Check out our post on TCF7L2, diabetes & carbs to find out.

Try to limit the intake of saturated fat (fatty meat, high-fat dairy) and omega-6 fatty acids (snacks, fried foods, pastry, vegetable oils. Replace them with fish, olive oil, walnuts, flaxseed, and hemp seeds in moderation.

Lifestyle

Specific lifestyle adjustments may work in synergy with diet to beat the negative metabolic effect of TCF7L2. In two studies described above, weight reduction and moderate exercise likely contributed to positive results [R, R].

The American Diabetes Association recommends the combination of moderate aerobic and resistance training, at least 150 min/week. Also, it’s crucial to reduce the sedentary lifestyle and interrupt longer periods of sitting every 30 min [R].

The American Heart Association recommends 150 min/week of moderate aerobic activity (or 75 min intense) plus strength training on at least two days a week [R].

Supplements

If your intake of fatty sea fish is low (less than three servings/week), consider supplementing with fish oil/omega-3. It has beneficial effects on blood lipids, high blood pressure, and different inflammatory conditions [R, R, R].

Aleksa Ristic

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Content

TCF7L2 in Metabolic Health The Impact of Dietary Fat on TCF7L2 Variants Your TCF7L2 Results for Response to Dietary Fat

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