How a Fat-Burning Gene Impacts Weight Gain (ADRB2)

The ADRB2 gene encodes the beta-2 adrenergic receptor, a vital part of the sympathetic nervous system. This receptor binds catecholamines, especially adrenaline (epinephrine), which increase cAMP levels [R].

The beta-2 receptors cause relaxation of the airways and smooth muscles (such as lungs) while contracting skeletal muscles (such as biceps). Their activity promotes breathing and circulation, slows down digestion, and improves physical performance [R, R].

Emerging research has been focusing on the metabolic roles of beta-2 and other adrenergic receptors. They control fat metabolism, insulin release, glucose production, and more [R, R].

ADRB2 encodes the beta-2 adrenergic receptor, which supports breathing, physical performance, and more. This receptor has essential roles in fat and glucose metabolism.

Beta-2 Receptors in Fat Metabolism & Obesity

Catecholamines control fat burning and energy expenditure, especially during caloric restriction (fasting) and exercise. Along with the primary beta-3 receptors in fat tissue, beta-2 receptors stimulate fat burning, resulting in energy and temperature release [R, R, R].

Leptin is a crucial metabolic hormone that helps burn fat stores by stimulating sympathetic activity and raising catecholamine levels [R].

The above pathways are often blunted in obesity due to a combination of factors such as [R, R, R]:

• Impaired function of stimulatory beta receptors
• Leptin resistance
• Increased activity of inhibitory alpha receptors
• Excess insulin levels, which suppress fat burning

Muscle sympathetic nerve activity (MSNA) is also vital for energy expenditure and weight control. People with low MSNA are more likely to become obese due to slower metabolism [R].

Beta-2 receptors bind catecholamines and stimulate fat burning, which results in energy and temperature release. This pathway is often blunted in obese people, leading to excess fat accumulation.

When it comes to body-weight measures, the two most studied ADRB2 variants are rs1042714 (Gln27Glu) and rs1042713 (Gly16Arg), but the evidence is mixed.

One meta-analysis gathered data from 18 studies examining the link between these two SNPs and obesity. According to their results, only rs1042714 showed a significant association—the “G” allele (Glu) carriers had 20% higher obesity rates [R].

An older meta-analysis came to a similar conclusion. However, the authors observed a significant link between rs1042714-G and obesity only in populations with lower frequencies of this allele, such as Asians and Native Americans [R].

In two studies with 150 women, those with the “G” allele had more fat mass and impaired burning [R, R].

The “G” allele at rs1042714 correlates with obesity, but the effect may be limited to specific populations.

Other Limitations

One Swedish study found that the link between rs1042714-G and obesity was significant only in women. On the other hand, in one Spanish study, it correlated with abdominal obesity only in men [R, R].

In Japanese subjects, this allele was associated only with subcutaneous (under the skin) fat accumulation. In Hispanic and African American people, it influenced only visceral (core) fat [R, R].

Some studies failed to confirm any correlation between this SNP and body-weight measures [R, R, R].

The precise link between rs1042714-G and obesity is yet to be confirmed and thoroughly explained. It depends on different factors, such as gender, ethnicity, and environment.

How It Works

As mentioned, the “G” allele at  rs1042714 may correlate with obesity, likely due to suppressed fat burning.

Normally, leptin helps burn excess fat stores by stimulating the sympathetic activity in fat tissue. However, according to one clinical trial, this pathway may be suppressed in people with the above SNP. The “G” allele carriers had higher leptin levels, but it failed to boost catecholamines, indicating leptin resistance [R].

Interestingly, this SNP doesn’t seem to alter the function of beta-2 receptors. Scientists are still looking for the exact mechanism behind its effects on sympathetic activity and fat burning. It may be just a marker for another variant with functional consequences [R].

This SNP correlates with impaired fat burning. According to preliminary research, it may prevent nervous system activation in fat tissue and contribute to leptin resistance.

SNP Summary

Primary SNP:

ADRB2 rs1042714

• ‘C’ = not associated with obesity
• ‘G’ = associated with obesity and higher fat mass

Population Frequency: Around 67% of European descendants carry at least one copy of the “G” allele. It’s much less common in other populations, especially African (26%) and East Asian (14%).