Brain hormone could help distinguish sugar and zero calorie sweeteners

Fruit flies have a set of neurones that fire only when they encounter real sugar – triggering the release of a hormone that is not released when they eat a non-calorific sweetener. And researchers suggest that humans possess the same ‘molecular machinery’.

While much research has suggested that zero calorie sweeteners are a valuable tool to aid weight loss, a small but significant number of studies have suggested that our bodies often compensate after consuming zero calorie sweeteners – though a potential mechanism for this has never been forthcoming.

Now researchers at the University of Michigan have identified a hormone-based system that helps the brain of a fruit fly differentiate between zero-calorie sweetness and calorie-laden sugars.

“We have identified the molecular and cellular nature of a sensor in the brain that detects the nutritional value of sugar through direct activation by nutritive sugars,” wrote the authors, led by Dr Monica Dus. “Dh44 neurons are activated specifically by nutritive D-glucose, D-trehalose, and D-fructose … and are not activated by non-nutritive sweeteners or sugars.” 

“Sugar-induced activation of these six central neurons resulted in secretion of the Dh44 neuropeptide, which transmits a signal to Dh44 R1 and R2 cells,” they said, writing in the journal Neuron

According to the team, the system provides a very elegant way for the brain to differentiate between real sugar and artificial or zero-calorie sweeteners since they taste similar.

Interestingly, the same ‘molecular machinery’ that distinguishes the two is also present on a larger scale in the guts and brains of humans, said Dus, who believes that human brains may also differentiate in the same way.

"We can ask, 'Do these genes work the same in humans, to tell real sugar from artificial sweetener?'" Dus said. "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."

Study details

Dus and her colleagues Greg Suh and Jason Lai from the New York University School of Medicine deprived fruit flies of food for several hours and then gave them a choice between diet, non-nutritive sweeteners and real sugar.

They found that 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 fuelled digestion and allowed the fly to lick more of the nutritious food.

On the other hand, when the fly licked the diet sweetener, the hormone and digestive reaction was not produced by the flies - 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, said the team.

If human brains work the same way, the discovery would help to explain why diet foods often do not satiate or satisfy us, and why we gain weight while dieting, said Dus.

While the fruit fly has roughly 100,000 neurons, the human brain has about 86 billion. However, 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, said the team.

Source: Neuron

Published online ahead of print, doi: 10.1016/j.neuron.2015.05.032

“Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila”

Authors: Monica Dus, et al