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Obesity Genes And Weight Loss After Gastric Bypass

Gastric bypass surgery is often considered the “gold-standard” for bariatric surgery and is now widely recommended for the treatment of severe obesity.

But, as I have often blogged before, no form of bariatric surgery guarantees success and patients are often disappointed with the amount of weight they lose (or that fact that there is some weight regain).

One of the major determinants of success after surgery is certainly faithful adherence to the rather strict dietary and lifestyle recommendations that patients have to follow in order to achieve and sustain the weight loss (no form of obesity surgery should ever be considered a “quick fix”).

But even in patients who diligently follow the behavioural advice, there are significant difference in the amount of weight they lose or keep off.

A new study by Christopher Still and colleagues from the Geisinger Obesity Research Institute in Danville, Pennsylvania, just published in OBESITY shows that genes that promote obesity may also result in poorer weight loss outcomes after gastric bypass surgery.

The researchers examined genetic variations in four genes that have previously been identified to increase the risk for obesity (FTO, INSIG2, MC4R, and PCSK1) in 1,001 individuals with extreme obesity who underwent Roux-en-Y gastric bypass surgery.

Individuals who had a higher number of obesity alleles not only tended to have higher pre-surgical BMI levels but also had less weight loss after surgery.

Thus, there were significant differences in postoperative weight loss trajectories across groups with low, intermediate, and high numbers of obesity alleles or numbers of homozygous genotypes, especially in patients with initial BMI levels below 50.

In these patients, weight-loss nadirs differed by 7% excess body weight across homozygous genotype groups and by almost 9% across cumulative allele groups. At 30 months following surgery, the mean amount of excess bodyweight lost was 79% for 0 alleles vs. 65% with 5+ alleles and 75% with 0 homozygous vs. 63% with 2+ homozygous genotypes.

These data suggest that response to surgical weight loss intervention is significantly influenced by genetic susceptibility to obesity – perhaps not all that surprising given the strong impact of genetic factors on the development of obesity in the first place.

Thus, as with non-surgical interventions, it just seems that even with bariatric surgery some people will need to work harder to lose and maintain the same amount of weight than others.

This does not take away from the importance of other factors (like following the recommended diet and activity plans) that may determine outcomes after surgery but just adds one more layer to why treatments that work well for some people does not work as well for others.

As blogged before – in obesity treatment one size never seems to fit all.

Edmonton, Alberta

Still CD, Wood GC, Chu X, Erdman R, Manney CH, Benotti PN, Petrick AT, Strodel WE, Mirshahi UL, Mirshahi T, Carey DJ, & Gerhard GS (2011). High Allelic Burden of Four Obesity SNPs Is Associated With Poorer Weight Loss Outcomes Following Gastric Bypass Surgery. Obesity (Silver Spring, Md.) PMID: 21311511


  1. Thanks for reporting on this study. It is interesting how much variation there is in both the susceptibility to obesity and response to surgical intervention – it seems that much of both are determined by genes. This finding supports the view that lifestyle modification should be included in treatment programs for those undergoing bariatric surgery!

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  2. One possible strategy is to offer those with higher number of obesity alleles the Duodenal Switch operation, instead of Gastric Bypass. Certainly one type of operation won’t fit all bariatric patients. Genetic study could be an interesting screening for the type of operation.

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  3. I appreciate this Dr Sharma, I think it’s important that the public (and politicians) are made very aware just how hard losing weight is for some people and that there is quite a lot of variation in how people will respond to interventions. I think there has been so much focus on differences BETWEEN groups over time (the epidemic) that we forget that most of the of variation WITHIN groups is still genetic.

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