Scientists Target a Gene in Mice That is Linked to Obesity

This obese mouse could slim down by shutting down its 14-3-3 zeta gene. And so might we one day. (Wikimedia Commons)

We have all heard the constant drumroll about the dangers of obesity. And yet it remains one of the major health issues in the U.S. and is a growing problem worldwide.

Obesity seems to have such a simple solution: Eat less and exercise more. But of course this is harder than it sounds. Evolution has hardwired us to love sugar and fat and to eat lots of both when they are in abundance.

Ideally what we need is some way to short-circuit this wiring to help our bodies respond differently to sugar and the fat. A new study from Nature Communications has uncovered a gene that just might help us with that.

The researchers found that when they removed the 14-3-3 zeta gene from mice, the mice had about 50 percent less of the bad “white” fat. And when they turned the gene up in other mice, these mice ended up with 22 percent more white fat.

This was not due to differences in diet as all of the mice ate the exact same thing. In fact, the mice that lost this gene gained less weight when put on a high fat diet.

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It looks like this gene plays an important role in telling the mouse how much fat to make based on what it is fed. Note, this gene isn't the whole story to explain why one mouse got plumper, but it is important enough to have a serious impact when tweaked. And it is likely that the equivalent gene in people plays a similar role.

Scientists aren’t going to engineer this gene away in people. That would be far too drastic. But what they hope to do is to someday find a drug that can affect this gene.

The idea would be that when the drug dampens the effect of the gene, people would gain less weight even with an unhealthy diet. They could have their cake and eat it too (although I certainly wouldn't advise that over a healthy salad!)

By targeting the 14-3-3 zeta gene, people may be able to have their cake and eat it too! (Wikimedia Commons)
By targeting the 14-3-3 zeta gene, people may be able to have their cake and eat it too! (Wikimedia Commons)

Not So Fast

As with any early study, you shouldn’t hold your breath until big pharma comes out with their new pill that keeps the fat away -- and even then, there may be reason for skepticism. This is all preliminary research.

Mice are not people. This gene seems to play a similar role in mice and people, and some early research would suggest that it is turned up in obese people versus those at a healthy weight. But we still need hard proof.

Another concern is that besides keeping these mice svelte, losing the gene also caused mild insulin resistance. This is a troubling result as insulin resistance is associated with Type 2 diabetes. Hypothetically, those who receive this treatment may look slender but suffer one of the side effects of being obese anyway.

A third concern is that we don’t know if dampening the gene in adults would have any effect. In the experiments in this study, the gene was missing over the whole life of the mouse. These mice developed in the womb and grew up without the 14-3-3 zeta gene.

It could very well be that the gene is involved in setting the body up to deal with converting food to fat. If this is the case, then turning it down in adults might not do anything.

Even with all of this, the gene seems like a promising target for further study.

Fewer and Smaller

Mice lacking the 14-3-3 zeta gene had fewer of these fat cells and they packed in less fat. (Wikimedia Commons)
Mice lacking the 14-3-3 zeta gene had fewer of these fat cells and they packed in less fat. (Wikimedia Commons)

When people gain weight, their fat cells first grow larger. Basically more and more fat is crammed into the cell until it gets too big.

Once the fat cell gets about four times its original size, it divides in two. These cells can then pack in more fat until they need to divide again.

What makes the 14-3-3 zeta gene so powerful is that it appears to affect both steps. Loss of the gene keeps the number of cells down and keeps them from growing in size as quickly. A one-two punch against obesity.

Importantly though, removing this gene did not shut off the whole process. The fat cells could pack in some fat, so these mice could gain weight.

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If scientists get it right, people who receive a therapy that targets this gene will not waste away to nothing. They will just get to have another Krispy Kreme doughnut without gaining weight.

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