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Researchers have found a genetic variation that can cause fat cells to increase in size more quickly. The millions of people with this variant are therefore at a greater risk of obesity. The researchers even speak of ‘guilt-free obesity’.
“Guilt-Free Obesity”
A few weeks ago, I wrote an article in which I asked the question of where that perfect weight loss pill remains. Not so much literally in the sense that one pill eliminates obesity from the world, but more as a question of when science actually helps in the fight against obesity. We know more and more about the physiological and psychological factors that influence the degree to which body fat is produced. More than enough to know that some people have to make much more effort for the same result due to other ‘settings’ of the body.
Last month, researchers from the Research Triangle announced that they had discovered another factor: A variation in a gene that millions of Americans have and which causes them to gain weight more quickly than others. Research conducted with mice has shown that the variation in a gene, called ankyrin-B, causes fat cells to absorb glucose more quickly, doubling their size. This, combined with changes in metabolism as people age and a diet high in fats, almost inevitably leads to obesity.
This variation that may have previously given people an advantage by creating a large energy reserve now makes achieving a normal weight almost impossible under current conditions. Senior author of the publication Vann Bennett and George Barth Geller of Duke University even speak in this regard of “guilt-free obesity”. Ankyrin-B could be a possible factor in the obesity epidemic. The results of their research were published last month in
Proceedings of the National Academy of Sciences (PNAS) [1].
“Obesity Gene”
Bennett discovered the protein ankyrin-B (ANK2) more than 30 years ago. It is present in every tissue of the body and works as a stabilizer in the membrane of cells. Bennett and other researchers have linked defects in ANK2 to various conditions including autism, muscular dystrophy, diabetes, and irregular heartbeat. In a study on the latter example, irregular heartbeat, Jane Healey conducted research in Bennet’s laboratory with mice a few years ago. She noted that the mice with an irregular heartbeat due to a mutation in ANK2 were thicker than others. To find out why this is the case, she developed mouse models with different human variants of the gene that encodes the protein ANK2.
Colleague Damaris Lorenzo then discovered that these mice became fatter more quickly because most calories were stored in fat tissue instead of being burned in other tissues. These findings were published in 2015 in the Journal of Clinical Investigation [2].
Bennett told ScienceDirect:
The problem is, we still didn’t know how this gene worked. There is this common belief in the field that much of obesity can be traced back to appetite and the appetite control centers that reside in the brain. But what if it isn’t all in our head?
To gain more insight into this, Lorenzo’s research group completely disabled the ANK2 gene. They repeated many of the same experiments as in 2015 with the mice with the different ANK2 mutations. In the mice with the disabled gene, they saw the same results. The mice became fatter and the white fat cells that store energy doubled in size, despite having the same diet and the same amount of exercise as normal mice. Moreover, the weight gain increased as they aged and the diet contained more fats.
They also discovered that the increased uptake of fats in fat cells ‘spilled over’ to the liver and muscles. The abnormal storage of fats in these tissues led to inflammation and disruption of insulin sensitivity. The latter is one of the characteristics of type 2 diabetes.
After a number of biochemical experiments, Lorenzo demonstrated that disabling the ANK2 gene changed the activity of Glut4, the protein that allows glucose to be absorbed by fat cells. This effectively opened the gates for glucose to flow into the fat cell more quickly.
Predisposition to Obesity
She then wondered if the same effects applied to other known human mutations in ANK2. For this, she cultured fat cells with these variants and found that they also absorbed glucose at an increased rate.
Bennett also explains to ScienceDirect that they have now determined that there is a clear mechanism that explains why some mice become obese without eating more. This gene could help identify people who are at increased risk of obesity. These people should then be advised accordingly to pay extra attention to their diet and exercise more.
Bennett points out, however, that their findings must first be tested in the human population. For this, they need to identify people with the ANK2 variants and, among other things, examine family history, determine body composition, and measure glucose uptake.
Not Everyone Guilt-Free?
Now, of course, the key question is: How many people carry such a variant? In the U.S., variants of ANK2 are present in 1.3% of white Americans and 8.4% of black Americans. Although this concerns millions, it does not seem to be the major cause of obesity. At least not when looking at the much higher obesity rates in the U.S.
But that’s not surprising, of course. There are many causes of obesity. This is just one example of factors contributing to this. Other examples we have discussed in recent months are proteins that affect your meal choice, proteins that convert white fat into fat-burning brown fat, and cells that influence hunger.
This does not make the solution easier immediately. A cure for innate predisposition to obesity is not yet in sight. Until then, we derive at best the knowledge to tell more and more people that they are at increased risk of obesity and why. In some cases, it may be possible to determine which types of nutrients pose a risk. In all cases, however, it remains a matter of choosing a healthy diet
and getting enough exercise. For one, however, a ‘healthy diet’ may prove much stricter than for another, and ‘enough exercise’ is also relative in this regard.
Personally, I would therefore not quickly speak of ‘guilt-free’ because that raises the question of what ‘blameworthy obesity’ is. With such a large number of physical and psychological factors that we do not determine ourselves, it is impossible to say what share remains for ‘free will’.
References
- Damaris N. Lorenzo, Vann Bennett. Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency. Proceedings of the National Academy of Sciences, 2017; 201708865 DOI: 10.1073/pnas.1708865114
- J Clin Invest. 2015;125(8):3087-3102.
- Streib, Lauren (8 February 2007). World’s Fattest Countries”. Forbes.
- The 10 Healthiest States in America”. University of Illinois at Chicago. Retrieved 18 September 2014.
