Sugar alters compounds that impact brain health in fruit flies: study

When fruit flies are exposed to a high sugar diet, key metabolites associated with brain health become depleted, according to a study posted on the website of the University of Michigan (UM) on Friday.

To examine how a high sugar diet affects the brains and bodies of fruit flies, the researchers compared a group of fasting flies to a group of fed flies. In the fed flies, the researchers skipped giving them dinner, then fed them a breakfast of moderately sweet glucose jelly the next day.

They mix the sugar jelly with blue or green dye, and after an hour, check the belly of the fly to make sure it’s eaten. To make sure the animals have eaten their fill, the researchers put the flies on a lickometer covered with the glucose jelly.

The researchers then freeze the sated flies as well as the group of fasting flies inside separate tubes. This stops the metabolic process, so that they can look at what’s going on in the flies’ brains at the moment of satiety. The researchers shake the tubes, which shatters the fly. A sieve separates the fly’s head, thorax, abdomen and legs. These parts were then sent to a company that uses mass spectrometry to measure the metabolites within the fly.

Using a tool called FlyScape, which produces visualization of the metabolic networks of fruit flies, the researchers look for patterns in metabolomics data.

They found that the flies’ metabolic profiles change rapidly during the quick transition from hunger to satiety, with the flies’ brains showing a larger change than their bodies. In particular, the high sugar diet lowered the levels of the brain metabolites N-acetyl aspartate, or NAA, and kynurenine.

The alteration of metabolites could impact how quickly the fly senses satiety, causing it to eat more.

Although scientists aren’t clear on the role of NAA in the brain, it appears to provide fuel for brain cells and balances osmolarity or regulates cell volume in the brain. Lower levels of another metabolite, kynurenine, are associated with depression.

“What we found was a metabolic remodeling,” said senior author Monica Dus, UM assistant professor of molecular, cellular and developmental biology. “It wasn’t just a gradual accumulation from an early to longer exposure, but by the seventh day on a high sugar diet, these fruit flies had a completely different metabolic profile.”

Ultimately, the study found that 20 metabolites, in addition to NAA and kynurenine, were impacted by sugar consumption.

“We examined what the changes in metabolites are that could be fundamentally perturbing the way that these cells were working,” said co-author Peter Freddolino, assistant professor of biological chemistry and computational medicine and bioinformatics at Michigan Medicine. “What this study tells us is what metabolomic pathways might be involved.”

In the next step, the researchers plan to dial down into how changes in these metabolites impact the brain, altering food intake and affecting other conditions such as sleep, learning and memory.

The study has been published in Nature Communications.