weight & body fat

nutrition

STAT3

Is Saturated Fat the Enemy of Your Flat Belly? (STAT3)

Written by Aleksa Ristic, MS (Pharmacy) on June 5th, 2020

The STAT3 gene encodes a protein with important roles in the immune system, inflammatory response, and more. Interestingly, certain variants of this gene link abdominal obesity with saturated fat consumption—read on to learn more.

The STAT3 Gene

The STAT3 gene is responsible for producing a transcription factor, a protein that regulates the expression of other genes. It plays a key role in the immune system and inflammatory response [R].

Research has identified STAT3 variants associated with cancer, autoimmune thyroid disorders, and inflammatory bowel disease [R, R, R].

Another interesting association is the link between STAT3, obesity, and dietary fats, which will be the focus of this article.

STAT3 in Weight Control and Metabolism

According to recent evidence, STAT3 plays an important part in insulin sensitivity and body weight regulation, likely due to interactions with TLR4 and leptin [R].

Mice lacking STAT3 in their brains are prone to weight gain and insulin resistance. They have increased appetite due to leptin resistance. The suppression of STAT3 in fat tissue causes the buildup and enlargement of fat cells, confirming the crucial metabolic roles of this protein [R, R].

STAT3 Variants and Abdominal Obesity

In a study of 1,754 French adults, different STAT3 variants showed a link with abdominal obesity (belly fat gain). People with the following variants had higher odds of abdominal obesity [R]:

rs8069645 (“G” allele)
rs744166 (“G” allele)
rs1053005 (“C” allele)
rs2293152 (“CC” genotype)

According to the study, men carrying 2+ risk alleles have about double the risk of abdominal obesity compared to those carrying 0 or 1 risk allele. Eating a diet high in saturated fat further increased the odds of abdominal obesity by as much as 32%.

Other types of fats, such as monounsaturated and polyunsaturated fats, do not appear to have the same effect on this genetic link.

While the association between STAT3 and abdominal obesity was significant only in men, women carrying these variants had higher rates of insulin resistance [R].

Four STAT3 variants may be associated with abdominal obesity in men, especially in those with higher intakes of saturated fat.

How It Works

As mentioned, STAT3 seems to suppress appetite and stimulate fat metabolism. More precisely, leptin achieves those effects partly by boosting STAT3 in the brain [R].

The above variants may lower STAT3 activity and gene expression, potentially contributing to insulin resistance and abdominal obesity [R, R].

Scientists are still exploring the mechanisms behind the observed negative effects of saturated fat. Apparently, saturated fatty acids activate the TLR4 receptors and thus trigger inflammation in fat tissue [R, R].

STAT3 variants likely reduce gene expression or activity. This may result in increased appetite and impaired fat metabolism, worsened by excess saturated fat.

Conflicting Results

The “C” allele at rs1053005 showed the opposite effect in a study of 1,742 Chinese subjects. Those carrying the “CC” genotype had significantly lower rates of obesity and abdominal obesity [R].

None of the studied STAT3 SNPs were associated with obesity in two studies of over 3,700 European participants [R, R].

Your STAT3 Results for Abdominal Obesity

SNP Table

variant	genotype	frequency	risk allele
rs8069645
rs744166
rs1053005
rs2293152

SNP Summary

Primary SNPs:

STAT3 rs8069645

‘A’ = No association with abdominal obesity in response to saturated fat
‘G’ = Associated with abdominal obesity in men, worsened by excess saturated fat
About 12% of people worldwide have the ‘GG’ genotype (highest risk)

STAT3 rs744166

‘A’ = No association with abdominal obesity in response to saturated fat
‘G’ = Associated with abdominal obesity in men, worsened by excess saturated fat
About 28% of people worldwide have the ‘GG’ genotype (highest risk)

STAT3 rs1053005

‘T’ = No association with abdominal obesity in response to saturated fat
‘C’ = Associated with abdominal obesity in men, worsened by excess saturated fat
About 10% of people worldwide have the ‘CC’ genotype (highest risk)

STAT3 rs2293152

‘G’ = No association with abdominal obesity in response to saturated fat
‘C’ = Associated with abdominal obesity in men, worsened by excess saturated fat
About 45% of people worldwide have the ‘CC’ genotype (highest risk)

Recommendations

Diet

Limit the Intake of Saturated Fat

As discussed, the above STAT3 variants may predispose some individuals to gaining belly fat from increased saturated fat consumption [R].

People with those variants would likely benefit from avoiding foods high in saturated fat, such as [R]:

Pork, bacon, and sausage
Pork fat and lard
High-fat dairy (butter, ghee, cheese, cream, etc.)
Coconut and palm oil
Different types of fast food

You can partly replace the above with healthy sources of unsaturated fatty acids, such as:

Fish
Avocado
Olive oil
Nuts
Seeds

Limit the intake of saturated fat, and replace it with other healthy fats to lessen the impact of your STAT3 variants.

Olive Oil

Other types of fat, such as monounsaturated fatty acids (MUFAs) don’t appear to have negative effects on STAT3-associated obesity. What’s more, the primary MUFA in olive oil, oleic acid, may stimulate STAT3 activity [R].

An olive oil-enriched diet was more efficient for weight loss than a standard low-fat diet in an 8-week comparison [R].

Lifestyle

Regular Exercise

Exercise may be a healthy way to increase the expression of STAT3, especially in older adults [R].

Resistance training is probably the best strategy to lose weight. In addition to promoting fat burning, it boosts different beneficial components that suppress appetite, improve mental health, and more [R, R, R].

Aerobic exercise (walking, running, swimming, etc.) has also caused significant reductions in belly fat in multiple studies [R, 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].

Exercise may increase STAT3 expression. Resistance and aerobic training are both great for weight loss and overall health.

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

The STAT3 Gene STAT3 Variants and Abdominal Obesity Your STAT3 Results for Abdominal Obesity

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