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Obesity-Gene Tells Cells to Grow Fatter

S u m m a r y :
A gene variant is telling cells to store more fat, thereby fuelling obesity, says a new study published in the Proceedings of the National Academy of Sciences.

Is Obesity A Choice?

Obesity is the result of a number of factors, like excessive eating and a sedentary lifestyle. However, the issue might not be as simple as this, suggests a new study. Obesity might also be fuelled by certain gene variants that predispose people to weight gain. The matter would not always be one of choice whereby the lifestyle of the person alone determines whether he will gain weight or not.

Fault-Free Obesity

The new study, conducted by a team from Duke University, shines the light on variants in a gene named ankyrin-B. Apparently, versions of this gene could be causing fat cells to take in glucose at a rate faster than normal such that these cells would grow more than twice their size. This would imply that part of weight gain is not the fault of the people expressing those genes; it’s not just about lifestyle and appetite and the brain. The study authors are calling this “fault-free obesity”.

“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?” says senior author Vann Bennett.

A Famine Gene That is Bad When Food is Abundant

These gene variants are carried by millions of people—what is their purpose? According to Bennett, the gene might have been useful to our ancestors during times of famine. But now that food is abundant in most regions of the world, ankyrin-B variants might be playing a role in the obesity epidemic.

Ankyrin-B was discovered by Bennett over 3 decades ago. This protein is found in all body tissues where they serve as anchor for important proteins that need to be held inside cell membranes. On the other hand, defects in ankyrin-B have been associated with diseases like autism, muscular dystrophy, aging, diabetes and irregular heartbeat. The link to weight gain was suggested by Jane Healey from Bennett laboratory some time ago: she had found that mice suffering from cardiac arrhythmia, the result of mutations in their ankyrin-B, were fatter than other mice. She had, then, developed mouse models with common human variants of the gene. Her colleague, Damaris Lorenzo, later discovered that these mice would pack on weight quickly, with the majority of their calories going into their fat tissues instead of other tissues to burn energy. What remained unknown was how the gene actually worked, explains Bennett. He adds that weight gain might not just be about appetite and the brain.

The mouse on the right lacks a gene for ankyrin-B, causing his fat cells to take in a lot of glucose that makes him fatter than the normal mouse at the left. Photo Credits: UNC Nutrition and Obesity Research Center.

More Weight Gain With Age & High-Fat Diets

In an attempt to solve this mystery, Lorenzo gathered her research group to investigate the processes behind the effects of this gene. The team inactivated the ankyrin-B gene from the fat tissues of mice, and repeated a number of experiments that had been done in other mouse models with mutant forms of the gene. These mice gained weight, and their white fat cells that would store energy increased to twice their size, in spite of the mice eating and exercising as much as normal ones. Moreover, the weight gain increased with ageing or with the consumption of high-fat diets.

“We quickly learned that the increased accumulation of lipids in fat cells “spilled over” to the liver and muscles,” says Lorenzo. “The abnormal accumulation of fat in these tissues led to inflammation and disruption of response to insulin, a hallmark of type II diabetes. A similar cascade of events is what often takes place in humans, and that is why obesity can be so detrimental to our health.”

Gain Weight Without Eating More

Another interesting finding is that removing or mutating ankyrin-B also affects the protein that allows the entry of glucose into fat cells, leading to open flood gates that let glucose molecules enter cells more quickly than normal. Furthermore, fat cells with these gene variants also take in glucose at a higher rate. Apparently, the disease originates in fat tissue, but with effects in other regions of the body.

“We found that mice can become obese without eating more, and that there is an underlying cellular mechanism to explain that weight gain,” says Bennett. “This gene could enable us to identify at-risk individuals who should watch what kind of calories they eat and exercise more in order to keep their body weight under control.”

Now, the findings must be confirmed in the general population. The team will have to study individuals with ankyrin-B variants.


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