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SH2B1

A Surprising Link Between Leptin and Obesity (SH2B1)

Written by Aleksa Ristic, MS (Pharmacy) on July 11th, 2020

Many different factors influence the link between leptin and weight control, but you probably haven’t heard of this one before. The SH2B1 gene encodes for a crucial metabolic protein and has a surprising link with obesity — learn the details and check your genes!

What is SH2B1?

The SH2B1 gene encodes SH2B adaptor protein 1, which controls the function of different hormones and growth factors, such as [R, R]:

Given its critical metabolic roles, slight changes in SH2B1 expression and activity can impact glucose and fat metabolism. Variants in this gene correlate with body-weight changes, insulin resistance, diabetes, and more [R, R, R, R].

Roles in Metabolism & Weight Control

According to studies on mice, SH2B1 activity in the brain is crucial for leptin signaling and thus impacts weight & energy balance [R]. Mice lacking this protein are obese, tend to overeat, and have increased leptin, insulin, and blood lipids [R, R].

On the other hand, increased SH2B1 expression protects against obesity and boosts glucose & fat metabolism [R].

More detailed experiments revealed that SH2B1 enables the “activation” of brown fat tissue (BAT). It enables leptin to stimulate the sympathetic nervous system (SNS) and boost heat production [R].

Large mutations in this gene result in severe early-onset obesity, while different SNPs correlate with more subtle weight changes [R, R].

SH2B1 is crucial for leptin signaling. It helps activate the fat tissue, boost metabolism, and control appetite. Mutations and SNPs in this gene are associated with obesity.

The Link Between SH2B1 Variants and Obesity

In a meta-analysis of over 116K people, the “G” allele at rs7498665 (Ala484Thr) was associated with a 0.15 increase in BMI [R].

An even larger meta-analysis of more than 200K subjects revealed the same correlation between rs7359397-T and BMI [R].

The “G” allele at rs7498665 was associated with obesity in three European studies:

2,900 German subjects — 23% higher obesity rates [R]
3,900 Swedish subjects — 13% higher obesity rates [R]
1,360 Belgian subjects — 26% higher obesity rates [R]

The above SNPs are always inherited together in most populations, so they represent a single genetic factor.

Rs7498665-G and rs7359397-T are associated with higher weight and obesity rates among European descendants.

How It Works

As discussed, SH2B1 helps boost metabolism and control weight & appetite by enhancing leptin sensitivity. Thus, obesity-associated variants likely reduce SH2B1 expression and impair leptin signaling [R, R, R].

Indeed, rs7498665 correlated with leptin levels in a study of 2,455 European (Caucasian) women [R].

Scientists haven’t confirmed the exact effects of the above SNPs in humans. They might mark another functional variant yet to be discovered.

Your SH2B1 Results for Obesity

SNP Table

variant	genotype	frequency	risk allele
rs7498665
rs7359397

SNP Summary

Primary SNPs:

SH2B1 rs7498665

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

SH2B1 rs7359397

‘T’ = associated with a higher BMI
‘C’ = not associated with weight

Population Frequency: These two SNPs are almost always inherited together, so they represent a single genetic factor. About 45% of European descendants carry one copy and 10% carry both copies of the minor alleles (G and T, respectively).

Interestingly, allele frequencies for these variants don’t match in African populations. Around 41% of the population carries rs7498665-G, while only 2.4% carries rs7359397-T.

Recommendations

Lifestyle

Regular Exercise

Physical exercise and long-term fitness may protect against leptin resistance [R, R, R]. What’s more, exercise can counteract your gene and help burn fat by boosting sympathetic (SNS) activity in the fat tissue [R, R].

Resistance and aerobic training are both fantastic approaches to weight loss. In addition to fat-burning, they improve mood, cognition, and overall health [R, R].

Cold Exposure

According to a large trial of 13,320 participants, cold exposure may enhance leptin secretion, enabling metabolic adaptation to lower temperatures [R]. Acute cold exposure boosts SNS activity and fat burning [R, R, R].

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.

Sleep Quality

Impaired circadian rhythm may contribute to leptin resistance and thus worsen the impact of your variant [R]. Restful sleep can normalize leptin signaling, while sleep deprivation impairs it and increases appetite [R, R].

A disrupted circadian rhythm may be why shift workers seem to be at an increased risk of obesity [R]. Short sleep duration correlated with weight gain and food cravings in multiple clinical trials [R, R, R, R, R].

Exercise, cold exposure, and proper sleep can counteract your variants and support weight loss.

Diet

Intermittent Fasting

Any form of calorie restriction is essential for weight loss, but people with SH2B1 variants may benefit from intermittent fasting in particular.

In a study of 34 men, 16/8 intermittent fasting slightly improved leptin sensitivity [R]. Fasting also stimulates SNS-mediated fat burning, potentially reducing the impact of your SNPs [R, R].

Fasting every other day 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].

Due to its metabolic effects, Intermittent fasting may be an ideal form of calorie restriction for people with SH2B1 variants.

Fruits & Vegetables

In animals, the consumption of polyphenol-rich fruits and vegetables prevented leptin resistance [R].

Vegetables are rich in soluble fiber, which may support weight loss. Fiber gets broken down by probiotic bacteria to produce butyrate, a fatty acid with potential weight-loss effects in preclinical research [R, R, R, R].

Polyphenols from various fruits, such as blueberries and apples, reduced weight in animal studies [R, R].

Polyphenol-rich fruits and vegetables may prevent leptin resistance and support weight loss, but clinical evidence is lacking.

Supplements

Berberine

Berberine supplementation reduced BMI and enhanced leptin sensitivity in 37 patients with metabolic syndrome. Another study observed an average weight loss of 5 lbs (2.3 kg) and lower blood lipids [R, R].

According to a 2020 review of human and animal studies, berberine might contribute to weight loss by improving gut microbiota, glucose & fat metabolism, and leptin signaling [R].

Garcinia

In obese animals, Garcinia cambogia extract enhanced glucose metabolism and leptin signaling [R, R, R].

Garcinia reduced weight and body fat in multiple clinical trials [R, R, R, R]. A review of 12 studies found that, on average, supplementation with Garcinia improved weight loss by about 2 pounds (0.88 kg) [R].

Yerba Mate

According to preclinical research, yerba mate may prevent leptin resistance [R].

Supplementation with yerba mate (3 g/day for 12 weeks) reduced body fat mass, body fat percentage, and waist-hip ratios of 30 obese participants [R].

Yerba mate (1,000 mg) before exercise increased fat metabolism and energy expenditure in a trial of 14 healthy participants [R].

Berberine, Garcinia, and yerba mate are herbal supplements that may counteract your genes by improving leptin resistance. They have shown benefits for weight loss, but the clinical evidence is limited.

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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What is SH2B1? The Link Between SH2B1 Variants and Obesity Your SH2B1 Results for Obesity

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A Surprising Link Between Leptin and Obesity (SH2B1)

What is SH2B1?

Roles in Metabolism & Weight Control

The Link Between SH2B1 Variants and Obesity

How It Works

Your SH2B1 Results for Obesity

SNP Table

SNP Summary

Recommendations

Lifestyle

Regular Exercise

Cold Exposure

Sleep Quality

Diet

Intermittent Fasting

Fruits & Vegetables

Supplements

Berberine

Garcinia

Yerba Mate

Disclaimer

More weight & body fat blogs

More nutrition blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

Essential

Bundle

Limited time offer 25% off

Ultimate Bundle

Policies

About

Navigation

Health reports