Obesity genes

BBC News tells us that the “slow metabolism ‘obesity excuse’ is true”. A mutation has been found that slows metabolism and causes people to become severely obese by early childhood.

The search for an obesity gene has been described as the ‘holy grail’ of obesity research.


The KSR2 gene is a potential candidate, it was previously found to be associated with obesity in mice. In this study researchers wanted to see if it was associated with obesity in humans.

The people who carried these gene mutations had a history of eating more as children, and had lower metabolic rates than would be expected. The researchers’ laboratory experiments suggest that the diabetic drug metformin may counteract some of the effects of the KSR2 variants.

Overall, these results suggest that KSR2 variants could be a contributing cause of severe obesity in some people.

Obesity is a complex issue. Not all people who have these variants are obese, and not all obese people have these variants. The environment and other genes also play a role.

The study was published in the peer-reviewed scientific journal Cell, so should have reliable data and information.

Previous studies have shown that mice genetically engineered to lack this gene are obese and have impaired glucose tolerance (which in humans are risk factors for type 2 diabetes).


The researchers looked at DNA from 2,101 severely obese people of mixed European descent, and 1,536 people from the general population in the UK (which may contain some severely obese individuals, but not as many as the selected severely obese group). They compared the sequence of nucleotides (the building blocks of DNA, represented by the letters A, C, T and G) in the KSR2 gene in all of these people. Once they had their results, they confirmed them in another sample of 238 cases and 1,117 controls.

They also:

  • looked at any changes they found in some of the family members of the severely obese people to see if all the people in the family who carried these changes were obese
  • compared characteristics, including metabolic rate, of 18 people who were obese and had KSR2 variants, and 26 equally obese people who did not carry any KSR2 variants
  • carried out a range of experiments and modelling to look at what effect the identified variants would have on how the gene, and the protein it produced, functioned in the cell
  • looked at mice genetically engineered to lack KSR2

When they looked at 44 family members of the severely obese people who carried KSR2 variants they found that 19 of them also carried the variants, and 18 of these people were overweight or obese.

However, some of the relatives were overweight or obese but didn’t carry the variants. This suggests that it wasn’t only the KSR2 variants that were affecting whether people in these families were obese or not.

Other findings:

  • Adults with KSR2 variants had a history of increased food-seeking behaviour as children, but by the time they were adults this was less prominent.
  • They had significantly lower metabolic rates than predicted based on their age, gender and body composition.
  • Heart rate was lower in obese adults with KSR2 variants than obese adults without these variants.
  • Obese adults with KSR2 variants had higher fasting insulin levels in their blood than those without the variants, as well as impaired glucose tolerance. These characteristics are linked to the development of type 2 diabetes.
  • Mice genetically engineered to lack KSR2 ate more than normal mice, and even if they were fed exactly the same food they gained more weight than normal mice.
  • Some of the effects of the variants identified on cells could be counteracted by treating the cells with the antidiabetic drug metformin.
  • Some of the obese adults with KSR2 variants were reported to have shown improvements in their weight in childhood when prescribed metformin for their severe insulin resistance.

We can do little about the genes we were born with, but we can change our lifestyles and behaviour. Your genetic make-up may make it harder for you to lose weight or maintain a healthy weight, but it does not make it impossible.

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