One study found that sugar remodels molecular memory in fruit flies

According to a University of Michigan study, a high-sugar diet reprograms the taste cells in fruit flies, blunting their sensitivity to sugar and leaving a “molecular memory” on their tongues.

By examining fruit flies, researchers Monica Dus, Anoumid Vaziri and collaborators found that high-sugar diets completely remodeled the taste cells of the flies, leaving a molecular memory that lasts even when the flies returned to healthy diets. The molecular memory of the previous diet could lock animals into a pattern of unhealthy eating behavior. Their findings were published in Advances in science.

“When we eat food, it only takes a few bites for it to go away. We don’t really think it’s something that could have this kind of lasting effect on our brains,” said Dus, UM professor of molecular, cellular, and developmental biology and senior author of the study. “But when the animals were moved to a different food environment, such as a healthy diet, they retained the molecular memory of the high-sugar diet in their cells. This shows that the past food environment can influence the animals’ future behaviors. “.

Specifically, the researchers found that a high-sugar diet reprogrammed the cells located in the mouth of fruit flies that sense sweetness, leading to a malfunction. This reprogramming involved an epigenetic regulator called Polycomb Repressive Complex 2.1, or PRC2. Epigenetic regulators are groups of enzymes that can affect how much and whether a gene is expressed by remodeling a material called chromatin. Chromatin encompasses the material of chromosomes in everything from plants to humans.

In this case, the research team discovered how PRC2 is distributed in the chromatin of neurons that sense sweet taste changes when flies eat a high-sugar diet. They found that this change activates some genes and silences others, particularly the genes involved in detecting sweetness.

“So through this very specific pathway, a high-sugar diet can silence the genes needed for sweet taste,” said Vaziri, a graduate student in Dus’s lab who led the work. “Even more interesting is that the effect of gene silencing is indeed persistent so that even when animals are removed from the high-sugar diet, the taste-associated genes have still changed and the animals continue to have sweet taste defects. “.

Fruit flies only have about 60 sweet taste cells in their mouthparts. After purifying these taste cells from flies that had been on a controlled diet and from flies that had been on a high-sugar diet for a week, the researchers used two techniques to identify the silenced genes. One of these techniques involves isolating ribosomes, particles that bind RNA to synthesize proteins, from these 60 cells and sequencing the associated messenger RNAs to determine if a gene has been silenced. Messenger RNA is a form of RNA that carries genetic instructions from DNA to ribosomes.

On the seventh day of a high-sugar diet, Vaziri found that more than 80% of the sweet taste genes had been silenced. This is because PRC2 changed its DNA binding and, in doing so, changed the “program / software” run by the taste cells. The new program didn’t make them respond to sweetness as well and almost reprogrammed their identity as sweet taste cells.

“We need to think of food not just as something we eat and then its effects go away, but actually as an experience that could impact our future behavior and food choices, similar to early childhood trauma that leaves a lasting effect on the adult brain, “Vaziri said.

To confirm that PRC2 was behind the gene silencing, the researchers mutated the complex to see if they could restore normal gene expression in the cells. By changing the complex, they found that the fly did not experience a decrease in the ability to perceive sweet flavors.

Interestingly, even flies that could still taste sugar were able to stay lean. Flies that experienced a decline in the ability to perceive sweet flavors became obese. The reason this occurs lies in some of the Dus lab’s previous research on how sugar interferes with satiety signals. When flies’ ability to taste sugar is dulled, they eat more and more sugar to achieve the same satiety levels. When their ability to taste sugar is not dulled, they finish eating sessions earlier.

“Instead of eating a whole bunch of cookies, they were able to stop at two,” Dus said. “It really reinforces the idea that these changes in taste are important to our ability to control food choice and intake.”