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ADRB3

The Master Fat-Burning Gene Impacts Weight Gain (ADRB3)

Written by Aleksa Ristic, MS (Pharmacy) on June 23rd, 2020

One receptor, encoded by the ADRB3 gene, is crucial for fat burning. Read on to learn about its link with obesity and get gene-based tips!

ADRB3: A Key Player in Fat Metabolism

The ADRB3 gene encodes the beta-3 adrenergic receptor. This receptor binds catecholamines and activates the sympathetic nervous system by increasing cAMP levels [R].

Beta-receptors impact vital processes such as breathing and blood flow but also have diverse metabolic roles. They control fat metabolism, insulin release, glucose production, and more [R, R].

Unlike beta-1 and beta-2, expressed throughout the body, the beta-3 receptor is mainly located in fat tissue. Once activated by catecholamines, It stimulates fat burning and heat production [R].

Leptin is a crucial metabolic hormone that helps burn fat stores by stimulating sympathetic activity and raising catecholamine levels [R]. These pathways are often blunted in obesity due to underactive beta receptors, leptin resistance, or other factors [R, R, R].

The ADRB3 gene helps make the beta-3 adrenergic receptors, found mostly in fat tissue. Catecholamines activate these receptors to boost fat burning and heat production.

The Link Between ADRB3 Variant and Obesity

Over 100 studies have examined the relationship between one ADRB3 variant—rs4994 or Trp64Arg— and body-weight measures.

One meta-analysis included 97 such studies, involving 44,800 participants. Among East Asians, those with the “G” allele had, on average, 0.31 units higher body mass index, which would equal 0.8-1 kg. In European descendants, the difference was four times smaller and wasn’t statistically significant [R].

The same group of authors conducted the largest study of 4,854 European (UK) subjects and confirmed the lack of association between this SNP and BMI [R].

In a meta-analysis of 16 studies and 12,500 children/adolescents, rs4994-G correlated with 23% higher obesity rates. Once again, the effect stemmed from East Asian subjects, who had 47% higher odds of obesity per the “G” allele [R].

A study of 329 adults from Saudi Arabia found a significant link between this SNP and obesity. People with the “G” allele also had a higher waist-hip ratio (WHR), blood lipids, leptin, and insulin levels [R].

Research has associated the same variant with other conditions, such as:

Diabetes [R, R]
High blood pressure [R]
Heart disease [R]

Those genetic effects were also more pronounced in East Asians.

The “G” allele at rs4994 correlates with significantly higher obesity rates, but the effect is mostly limited to East Asian populations.

How It Works

The A>G switch at rs4994 changes one amino acid in the beta-3 receptor structure. The “mutant” receptor had a reduced ability to produce cAMP in test tubes [R, R].

In a study on human fat cells, this variant produced receptors that were less efficient at burning fat [R].

According to clinical trials, this variant is also associated with higher leptin and lower adiponectin levels, indicating impaired fat metabolism [R, R].

The “G” allele at rs4994 changes one amino acid in the beta-3 receptor structure, reducing its ability to burn fat.

Your ADRB3 Results for Obesity

SNP Table

variant	genotype	frequency	risk allele
rs4994

SNP Summary

Primary SNP:

ADRB3 rs4994

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

Population Frequency: About 15.5% of European descendants carry the “G” allele. It’s more common in East Asian (24%) and South Asian (30%) populations.

Recommendations

Lifestyle

Exercise

Exercise is the best way to overcome your genetic effect and burn fat by activating beta-3 receptors [R, R, R]. It further supports this pathway by improving leptin sensitivity [R, R, R].

Resistance training is a great choice when it comes to weight loss. In addition to promoting fat burning, it boosts BDNF, endorphins, and other beneficial hormones and components that suppress appetite, improve mental health, and more [R, R].

Aerobic exercise (walking, running, swimming, etc.) has significantly reduced belly fat in multiple studies [R, R].

Regular exercise can help you activate beta-3 receptors, shed extra pounds, and improve overall health.

Cold Exposure

Acute cold exposure boosts sympathetic activity in fat tissue, partly by stimulating beta-3 receptors [R, R, R]. It also raises adiponectin, which is essential for people with rs4994-G [R].

Cold exposure increases metabolism and energy expenditure as the body has to adapt and produce more heat. In a clinical trial of 50 healthy men, those exposed to a cold environment overnight had a 10% increase in metabolism after one month [R].

Cold showers are the easiest way to practice acute cold exposure year-long, regardless of your climate conditions. During the winter, try to engage more in outdoor activities.

Take cold showers to lessen the impact of your variant and enhance weight loss.

Limit Alcohol Intake

Excess alcohol consumption suppresses fat burning by blocking beta-adrenergic receptors [R, R].

Alcohol is a significant source of calories, delivering 7 kcal per gram. Although moderate alcohol consumption is unlikely to impact weight gain, heavy drinking has a robust link with obesity [R].

In two studies of over 11,600 participants, increased alcohol consumption correlated with abdominal obesity, which is a strong risk factor for heart disease [R, R, R].

Alcohol suppresses fat burning by blocking beta receptors. Increased alcohol intake is associated with weight gain and abdominal obesity.

Diet

Intermittent Fasting

Calorie restriction in any form is essential for weight loss, but intermittent fasting may be ideal for people with rs4994-G. Fasting stimulates fat burning mediated by catecholamines, potentially reducing the impact of this SNP [R, R].

In one trial, fasting every other day (with 25% of daily calories) for 12 weeks caused 32 people to lose 12 pounds more than those who followed daily calorie restriction [R]. A meta-analysis of 11 studies found intermittent fasting as efficient as regular calorie restriction for weight loss [R].

Coffee & Tea

Caffeine, the main active ingredient in coffee and tea, has well-known fat-burning properties. It boosts cAMP and indirectly activates beta-3 receptors by increasing adrenaline [R, R, R].

In a 2019 meta-analysis of 12 studies, coffee consumption correlated with slightly lower weight and waist circumference, especially in men [R]. Green tea has shown moderate benefits for weight loss, but the evidence is inconclusive [R, R].

Keep in mind that a high intake of caffeine can cause adverse effects such as insomnia, anxiety, increased heart rate and blood pressure, increased urination, and muscle twitching [R].

Practice intermittent fasting and drink coffee & tea in moderation to activate your beta-3 receptors and enhance fat burning.

Supplements

Butyrate is a short-chain fatty acid produced by our gut probiotics. In a study on mice, butyrate enhanced fat burning via the beta-3 receptor [R].

Animal studies indicate the potential of butyrate to support weight gain [R, R]. It may also stimulate fat burning in humans, but the evidence is limited [R].

Butyrate is available as a supplement, but the best way to obtain it is by feeding resistant starch to the gut flora, which has a crucial role in weight control [R].

Resistant starch may support weight loss, but the research is mostly limited to animals [R, R, R]. It increases PYY, a hormone that promotes satiety and fullness [R, R, R, R].

Butyrate may counteract your ADRB3 variant and improve weight control. Obtain it by taking resistant starch or butyrate supplements.

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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ADRB3: A Key Player in Fat Metabolism The Link Between ADRB3 Variant and Obesity Your ADRB3 Results for Obesity

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The Master Fat-Burning Gene Impacts Weight Gain (ADRB3)

ADRB3: A Key Player in Fat Metabolism

The Link Between ADRB3 Variant and Obesity

How It Works

Your ADRB3 Results for Obesity

SNP Table

SNP Summary

Recommendations

Lifestyle

Exercise

Cold Exposure

Limit Alcohol Intake

Diet

Intermittent Fasting

Coffee & Tea

Supplements

Disclaimer

More weight & body fat blogs

More nutrition blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

🧬 DNA Day 30% Off

Essential

Bundle

🧬 DNA Day 35% Off

Ultimate Bundle

🧬 DNA Day 50% Off

Individual DNA Reports

🧬 DNA Day 50% Off

Methylation Pathway - MTHFR Test

Histamine Intolerance DNA Pathway Report

Gut Health, Digestion & IBS DNA Report

Autoimmune Disease Risk & Prevention DNA Report

See all reports

Policies

About

Navigation

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