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Fake sugars don’t trick fruit fly brains

If our brains work the same way as the fruit flies', the findings help explain why diet foods don't satiate or satisfy us, and we gain weight while dieting, according to Monica Dus. (Credit: Abby/Flickr)

Why is it that when we eat an entire sleeve of low-calorie cookies, we’re stuffing ourselves with more food 15 minutes later?

One theory to explain the phenomenon is that artificial sweeteners don’t contain the calories or energy that evolution has trained the brain to expect from sweet-tasting foods, so they can’t fool the brain into satisfying hunger.

However, until now, it hasn’t been clear how organisms distinguish between real sugar and artificial sweetener.

Fruit fly brains

A new study shows how the brain of a fruit fly differentiates between the two. Because that molecular machinery is present in the guts and brains of humans on a larger scale, researchers believe human brains will differentiate in the same way. Fruit flies and humans share about 75 percent of the same disease-causing genes.

“We can ask, ‘Do these genes work the same in humans, to tell real sugar from artificial sweetener?'” says Monica Dus, assistant professor of molecular, cellular, and developmental biology at the University of Michigan.

“The bits and pieces are there, so it is really possible that these genes work in a similar way. Plus, we knew that the human brain could tell the difference between real and fake sugar, we just did not know how.”

Sweet means sugar

For the study, published in the journal Neuron, researchers deprived fruit flies of food for several hours and then gave them a choice between diet, non-nutritive sweeteners and real sugar. When the flies licked the real sugar, it activated a group of six neurons that released a hormone with receptors in the gut and brain.

The hormone fueled digestion and allowed the fly to lick more of the nutritious food. But, when the fly licked the diet sweetener, it never produced this hormone/digestive reaction because zero-calorie sweetener has no nutritional or energy value.

In every case, the flies abandoned the artificial sweetener and chose the regular sugar because the starved flies needed the energy provided by the calories in the real sugar.

From an evolutionary perspective, sweet taste means sugar (traditionally from fruit or high concentrate carbohydrates) and a subsequent big energy boost. Fruit flies can’t call out for pizza—their brains expect calories if they eat something sweet, and that’s why they chose the regular sugar, Dus says.


If our brains work the same way, this helps explains why diet foods don’t satiate or satisfy us, and we gain weight while dieting, she says. It’s analogous to a person eating that entire sleeve of low-calorie cookies and the body saying it’s still hungry. The snacking continues until the body gets something with nutritional value that satisfies energy needs.

The fruit fly has roughly 100,000 neurons and the human brain has about 86 billion. The six neurons identified in fruit flies are in roughly the same spot in humans, which removes an immense amount of guesswork and lets researchers zero in on a location. The neurons fire only when they encounter real sugar, which provides a very elegant way for the brain to differentiate between real sugar and artificial sweeteners since they taste similar.

In two previous studies, researchers found that flies that couldn’t taste preferred real sugar to a zero-calorie sweetener, which underscores the theory of energy preference. They also characterized a neural circuit, dubbed Cupcake+, which functions as a behavioral on/off switch for eating. Turning on the Cupcake neurons makes the fruit flies stop “feeling” hungry, Dus says.

Greg Suh and Jason Lai of New York University School of Medicine are coauthors of the study.

Source: University of Michigan