weight & body fat

nutrition

GNPDA2

How Does this Enzyme Affect Weight Gain & Loss? (GNPDA2)

Written by Jasmine Foster, BSc, BEd on June 23rd, 2020

GNPDA2 encodes an enzyme that may both decrease appetite and increase fat deposition. What is its genetic link to obesity? Read on to learn more.

What is GNPDA2?

GNPDA2 encodes an enzyme that converts glucosamine-6-phosphate to fructose-6-phosphate and ammonium as part of what’s called “aminosugar metabolism” [R].

This reaction is believed to be a part of sugar and fat metabolism. One study that investigated the effects of high and low GNPDA2 found that it increased fat deposition and altered the expression of genes that affect the insulin response [R].

The GNPDA2 enzyme is primarily active in the brain and some research suggests it could play a role in appetite regulation [R, R].

In chickens, overexpression of GNPDA2 led to increased PGC1α. This protein activates many other genes and has been heavily implicated in energy metabolism and autophagy. PGC1α is highly expressed in brown fat and muscle tissues, further reinforcing GNPDA2’s role in metabolism and energy regulation [R, R].

GNPDA2 encodes an enzyme involved in sugar and fat metabolism. It appears to regulate fat deposition, appetite, insulin response, and autophagy, among other possible functions.

How Does GNPDA2 Affect Weight?

Researchers believe that GNPDA2 increases rates of obesity through its action in the hypothalamus region of the brain. Levels of GNPDA2 enzyme in the hypothalamus increase with leptin [R, R, R].

Leptin is the primary hormone that suppresses appetite and makes us feel full. It is released after we have eaten a meal and in response to some other triggers. Researchers have found that GNPDA2 is released around the same time as leptin, but they are not sure whether it is a cause or consequence of leptin release—or whether GNPDA2 is released because of the same root signals as leptin [R, R].

One study suggests that GNPDA2 may also have something to do with fat deposition and the creation of new fat tissue. In this study, overexpression of GNPDA2 in stem cells led to increased accumulation of fat; a lack of GNPDA2 led to decreased accumulation of fat [R].

High GNPDA2 may therefore be a double-edged sword: it could decrease appetite (in the hypothalamus), but increase the rate of fat deposition (elsewhere in the body).

GNPDA2 may both promote fat deposition and decrease appetite through leptin. Its relationship with weight gain is complex and not fully understood.

GNPDA2 Variants & Weight Gain

Three GNPDA2 variants have been associated with weight gain. The better-studied of the two is rs10938397, at which the minor ‘G’ allele has been linked to childhood obesity, increased body mass index (BMI), and increased waist circumference (WC) [R, R, R, R].

The other two variants, rs1996023-T and rs16858082-T, have been associated with obesity in Chinese children [R, R].

It is not clear whether the potentially detrimental allele of any of these SNPs increases or decreases GNPDA2 activity.

Your GNPDA2 Results for Weight Gain

SNP Table

variant	genotype	frequency	risk allele
rs10938397
rs1996023
rs16858082

SNP Summary and Table

GNPDA2 rs10938397

‘A’ = Not associated with weight measurements
‘G’ = Associated with obesity, increased weight, and increased BMI in multiple studies
About 54% of all people have at least one copy of the ‘G’ allele.
The ‘G’ allele is more common in people of European (66%) and American (64%) descent and less common in people of African descent (36%).

GNPDA2 rs1996023

‘T’ = Associated with obesity in Chinese children
‘G’ = Possibly protective against obesity in Chinese children
Most people worldwide (77%) have at least one copy of the ‘T’ allele.
The ‘T’ allele is more common in people of African (85%) and South Asian (86%) descent and much less common in people of East Asian descent (53%).

GNPDA2 rs16858082

‘T’ = Associated with obesity in Chinese children
‘C’ = Possibly protective against obesity in Chinese children
Most people worldwide (78%) have at least one copy of the ‘T’ allele.
The ‘T’ allele is more common in people of African (85%) and South Asian (87%) descent and much less common in people of East Asian descent (53%).

Recommendations

Regular Sleep Schedule

Children who get adequate sleep at critical times during their development are less likely to become obese, and at least one study suggests that this link has something to do with GNPDA2 [R].

According to a Chinese study, children with the potentially detrimental GNPDA2 variant rs16858082-T were even more likely to become obese if they got less than eight hours of sleep per night. Children with this variant were protected against obesity if they slept more than ten hours per night, by contrast [R].

Researchers aren’t sure whether sleep increases or decreases GNPDA2; however, this study suggests that getting enough sleep helps regulate GNPDA2 as well as weight.

Research over the past few decades has recognized the importance of circadian biology in obesity. Scientists think that circadian biology may have a massive influence on energy balance and metabolism [R].

According to another theory, a disrupted circadian rhythm may be why shift workers seem to be at an increased risk of obesity [R].

Short sleep duration has been associated with weight gain in many studies. A meta-analysis of 30 studies and over 630,000 people associated short sleep duration with a 55% higher incidence of obesity in adults and 89% in children [R, R, R].

Poor sleep can increase hunger and cravings and disrupt hunger hormones like ghrelin and leptin [R, R].

Children who don’t get enough sleep are more likely to become obese than those who do, and this relationship is more dramatic in those with detrimental GNPDA2 variants.

Avoid Fried Food

According to one study, people with potentially detrimental GNPDA2 variants may be at increased risk of weight gain when they eat fried food [R].

Fried food is also well understood to promote weight gain in general, as frying tends to increase the energy density of food and increase the proportion of saturated fats present. Some researchers have also suggested that eating a lot of fried food may promote leptin resistance, thereby increasing food intake overall [R, R, R].

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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

What is GNPDA2? How Does GNPDA2 Affect Weight? GNPDA2 Variants & Weight Gain Your GNPDA2 Results for Weight Gain

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