As we get older, it can be hard to fend off the ever increasing diameter of our waistline’s spare tyre. As we become more worn, and start balding (much like an old tyre) the pressure can mount to reverse our over-inflation.
Okay, that’s enough of the stating the obvious through rubberised metaphors but it is a dilemma that many of us face as we age. However, (as little consolation) there is now more scientific evidence to back up that it could be in our genes – rather than simply a lifestyle decision to let ourselves go or a reduction in vanity as we become wiser.
Researchers have shown that two different mutations in a gene called ankyrin-B cause cells to suck up glucose faster than normal, fattening them up and eventually triggering the type of diabetes linked to obesity.
The more severe of the two mutations R1788W, the name of which may have been taken from the label of a high-powered microwave, is carried by nearly one million Americans. The milder mutation L16221, while sounding like a new model of smartphone, is shared by 7% of the African population.
These finding, which can be found in the Journal of Clinical Investigation, could help identify at-risk individuals who might be able to combat its effects by eating better and exercising more.
It was Acceptable in the 80s
Vann Bennett (M.D., Ph.D) of Duke University School of Medicine explained how historically we had to trade in our flares for elasticated waistbands. He said: “This is one of the first examples of a susceptibility gene that would be manifested through modern lifestyle.
“The obesity epidemic really took off in the 1980’s, when sugary sodas and French fries became popular. It’s not like we suddenly changed genetically in 1980, but rather we have carried susceptibility genes that were exacerbated by this new diet.”
He added: “We think our findings are just the beginning, and that there are going to be many genes like this.”
During the latest studies researchers found that animals with two copies of the R1788W mutation made less insulin than normal mice. Despite this, their blood glucose levels were normal. So the team performed the rodent equivalent of a glucose tolerance test (we can only speculate that this may have been facilitated by injecting Lucozade into wedges of cheese) to determine how quickly glucose was cleared from the bloodstream in the mutant mice. To their surprise, the mutant mice metabolised glucose more quickly than normal mice.
Effects of Glucose Testing on DNA Mutation
One of Bennett’s students, Jane Healy said: “We thought that the main problem in these mice would be with the beta cells that produced and secreted insulin. Instead, our most significant finding lay with the target cells, which took up much more glucose than expected.”
Normally glucose does not enter cells and tissues all on its own, it relies on a second molecule – which remains within the cell until the glucose arrives. When insulin is present the molecule then opens the cell up to let glucose in and when insulin goes away (as all guests should, as not to outstay their welcome) the molecule transporters close the cell up again.
However, Damaris Lorenzo (another Ph.D), found that was not the case with the mutant mice. He discovered that the mice had lots of the aforementioned molecule on the surface of their muscle and fat cells even when there was not any insulin around. That meant glucose could flow in with greater ease.
This was an advantage when they were young, because it protected the animals from low insulin levels. But when the mice got older or switched to a particularly high-fat diet, it made the mice fatter and eventually led to them becoming insulin resistant. If these fatter-older mice could talk, no doubt they would be complaining that these young, slim, teenage mutant-mice don’t know how good they have it nowadays.
Researchers believe that these mutations may have occurred to provide an evolutionary advantage. More specifically suggesting that hunter-gatherers, who were not as effective at chasing down their more mobile food sources, needed to gain as much fat as possible to avoid starvation.
Now that high-fat and calorific foods are plentiful in much of the world, these variants put people at risk for modern afflictions like obesity and diabetes.
Not wishing to be solely the barer of bad news, there is an upside to this discovery, as a better understanding of these mutations could lead to more appropriately catered (in both senses of the word) treatments in the future. Lorenzo said: “If people with these mutations are detected early enough, they become prime candidates for intervention with personalised therapies.
“That might involve specific strategies to manage their deficits in insulin secretion, as well as adhering to normal diet and an active lifestyle, with the hope they can avoid the metabolic diseases that could severely impair their quality of life.”
Next researchers will explore whether the effects of such glucose metabolism tests can be used to better understand such mutations within humans and also how this can be utilised for future treatments. We wish them every success with unravelling the mysteries of these particular mutations, otherwise it may have been a lot of work to effectively repeat the ageing mantra of ‘eat right and exercise’.