weight & body fat

inflammation & autoimmunity

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TNF

Genetics of Inflammation, Obesity & Insulin Resistance (TNF)

Written by Aleksa Ristic, MS (Pharmacy) on June 9th, 2020

The TNF gene helps produce TNF-alpha, a crucial inflammatory cytokine that impacts glucose metabolism and weight control. One variant in this gene is associated with body fat and obesity — read on to learn the details!

TNF Gene and Inflammation

The TNF gene encodes a protein called tumor necrosis factor-alpha (TNF-alpha or cachexin), which plays a central role in the immune response and inflammation [R].

This cytokine, a type of cell signaling protein, is produced by different immune cells. It stimulates phagocytosis— “swallowing” of damaged cells and pathogens— and activates various inflammatory pathways, including NF-κB [R, R, R].

Variations in the TNF gene may cause improper production of TNF-alpha and contribute to a range of inflammatory conditions, such as autoimmune diseases, depression, and cancer [R, R, R].

The TNF gene encodes TNF-alpha, a crucial inflammatory cytokine. Variants in this gene are associated with a range of inflammatory conditions.

TNF-Alpha in Metabolism & Weight Control

Emerging research in the last couple of decades has found a robust link between inflammation, metabolic disorders, and obesity. Fat tissue can release inflammatory cytokines, which, in turn, impair glucose metabolism and contribute to weight gain [R].

In the early 90s, scientists “unlocked” this research area by observing higher TNF-alpha expression in the fat tissue of obese mice. The levels of this cytokine correlate with the degree of obesity and insulin resistance. More precisely, TNF-a impairs the function of insulin receptors [R, R]

Obese mice lacking TNF-a or its receptor are protected against insulin resistance, confirming its crucial role as a link between these conditions [R].

Additionally, TNF-a may stimulate the fat cells to release excess amounts of leptin into the bloodstream and contribute to leptin resistance [R].

Excess TNF-alpha released from the fat tissue can impair glucose metabolism and cause leptin resistance. Its levels correlate with the degree of obesity.

The Link Between TNF Variant and Obesity

Out of many SNPs in the TNF gene, obesity-related research has mostly focused on rs1800629 or G-308A.

In a meta-analysis of eight studies and 3,562 subjects, the “A” allele at this position was associated with 23% higher obesity rates. The effect was significant only in white (Caucasian) people between 41 and 60 years old [R].

Three clinical studies of 590 total participants confirmed a link between this variant and weight, fat mass, and waist circumference. All of them observed a stronger effect on women [R, R, R].

Trials with people from Iran, Tunis, and South Korea failed to detect a correlation between rs1800629 and obesity, limiting its impact to European descendants [R, R, R].

The “A” allele at rs1800629 correlates with higher fat mass and obesity rates. The effect is strongest among white, middle-aged women.

How It Works

As mentioned, excess TNF-alpha plays a central role in obesity, insulin resistance, and impaired leptin signaling.

The “A” allele at rs1800629 increases gene transcription and TNF-alpha levels, potentially contributing to weight gain [R].

Your TNF Results for Obesity

SNP Table

variant	genotype	frequency	risk allele
rs1800629

SNP Summary

Primary SNP:

TNF rs1800629

‘A’ = associated with higher obesity rates and fat mass
‘G’ = not associated with obesity

Population Frequency: About 25% of European descendants carry one copy, and only 1% carry both copies of the “A” allele. This allele is less frequent in East (11%) and South (10%) Asian populations.

Recommendations

Lifestyle

Stress Reduction

According to a large meta-analysis of 34 studies, psychological stress significantly raises blood levels of TNF-alpha and other inflammatory molecules. TNF-a is one of the factors that link chronic stress and inflammation [R, R].

Stress is a well-known obesity contributing factor. It increases cortisol and dynorphin, both of which cause weight gain [R, R, R].

Additionally, stress makes the brain resistant to serotonin and dopamine, which may increase appetite and block the rewarding effects of food [R, R, R].

Psychological stress can worsen the impact of your variant by raising TNF-alpha. Stress reduction is a crucial step toward successful weight loss.

Improve Sleep Quality

Circadian Rhythm

Circadian rhythm disruption contributes to inflammation and spikes TNF-a. It’s associated with leptin resistance and obesity in animals [R, R].

Research over the past few decades has recognized the importance of circadian biology in obesity, energy balance, and metabolism [R].

A disrupted circadian rhythm may be why shift workers seem to be at an increased risk of obesity [R].

Sleep Duration

Sleep deprivation and chronic insomnia correlate with higher TNF-alpha levels [R, R].

Researchers have linked short sleep duration with weight gain in several studies. They suggest that poor sleep may increase hunger and cravings and disrupt appetite-controlling hormones like ghrelin and leptin [R, R, R, R, R].

Circadian rhythm disturbance and sleep deprivation may mimic your variant by raising TNF-a. Proper sleep quality is essential for metabolic health and weight control.

Mediterranean Diet

Based on clinical data, specific foods may decrease inflammatory markers such as TNF-alpha. These include:

Fruits and vegetables [R]
Olive oil [R]
Fish oil/omega-3 [R, R]

Vegetables are rich in soluble fiber, which may support weight loss. Polyphenols from various fruits (including blueberries and apples) led to lower weight in animal studies as well [R, R, R, R].

In young, overweight men, the inclusion of either lean or fatty fish or fish oil as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after four weeks compared to a similar diet without seafood or a supplement [R, R].

In a review of 11 clinical studies, an olive oil-enriched diet significantly reduced BMI and waist circumference. Unlike oil in its natural form, supplementation with capsules was not effective [R].

The Mediterranean diet is abundant in all of the above foods. Studies have confirmed its potential to reduce TNF-alpha and is associated with lower inflammation [R, R].

The Mediterranean diet has shown beneficial effects for a range of metabolic disorders, including insulin resistance [R, R, R].

The Mediterranean diet may lessen the impact of your variant, improve insulin resistance, and support weight loss.

Supplements

Green Tea Extract/EGCG

The primary catechin from green tea, EGCG, inhibited TNF-a in multiple animal trials [R, R, R].

According to a review of 11 studies, green tea extract or EGCG can slightly improve weight loss and maintenance. However, a Cochrane database review of 14 studies regarded the change in weight as nonsignificant in most studies, so the evidence is inconclusive [R, R].

The majority of weight loss trials used special extracts with higher concentrations of active ingredients (catechins and caffeine), compared with regular tea. Hence, it may be necessary to take an EGCG-rich green tea extract for beneficial effects [R].

Green tea extract rich in EGCG and caffeine may counteract your TNF variant and contribute to weight loss, but the evidence is inconclusive.

Hops

The active ingredients of hops, xanthohumol, suppressed TNF-mediated inflammation in preclinical research [R, R, R].

In a trial on 200 overweight people, hops extract reduced body fat, especially in the belly [R]. Both hops extract and xanthohumol reduced body weight in multiple studies on overweight mice and rats [R, R, R, R, R].

The combination of hops and acacia active components improved several symptoms of metabolic syndrome. Combined with diet changes and exercise, it reduced triglycerides, total cholesterol, and LDL in a trial of 23 people. The combination may also improve insulin sensitivity, which is crucial for people with elevated TNF-alpha [R, R].

Hops extract can suppress TNF-mediated inflammation. According to limited clinical evidence, it may boost fat metabolism, reduce blood lipids, and improve insulin sensitivity.

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.

More inflammation & autoimmunity blogs

How to Combat Histamine Intolerance Through Genetics (DAO) Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT) How to Tell if You’re Lectin Sensitive Using Your Genetic Data (CNR1) Are You Sensitive to Lectins? (MTHFR) Fight Oxidative Stress, Inflammation, and Brain Fog (PARP1) Is This Gene Causing Your Autoimmune Problems? (PTPN22) Are You Genetically Susceptible to Post-Treatment Lyme? (ABCB1) A Key Genetic Player in Autoimmunity (HLA-B) Is This Inflammation Gene Reducing Your Intelligence? (TNFSF9) Can You Manage Allergies and Asthma by Balancing Methylation? (MTHFR)

Content

TNF Gene and Inflammation The Link Between TNF Variant and Obesity Your TNF Results for Obesity

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