Study finds sugar reshapes molecular memory in fruit flies

A diet high in sugar reprograms the taste cells of fruit flies, reducing their sensitivity to sugar and leaving “molecular memory” on their tongue, according to a study from the University of Michigan.

Examining fruit flies, researchers Monica Dus, Anoumid Vaziri, and colleagues found that diets high in sugar completely reshaped the taste cells in flies, leaving a molecular memory that lasts even after the flies resumed healthy eating. The molecular memory of the previous diet could lock the animals into a pattern of unhealthy eating behavior. Their results were published in Scientific advances.

“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 that kind of lasting effect on our brains,” said Dus, professor at the ‘UM of Molecular, Cellular, and Developmental Biology and lead 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 may influence future animal behaviors. . “

Specifically, the researchers found that a diet high in sugar reprograms cells in the mouths of fruit flies that feel the sweetness, leading them to dysfunction. This reprogramming involved an epigenetic regulator called Polycomb Repressive Complex 2.1, or PRC2. Epigenetic regulators are groups of enzymes that can affect how well and whether a gene is expressed by reshaping a material called chromatin. Chromatin comprises 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 experience sweet taste changes when flies follow a diet high in sugar. They found that this change turns on some genes and silences others, especially the genes involved in sensing sweetness.

“So, thanks to this very specific pathway, a diet high in sugar can silence the genes necessary for a sweet taste,” said Vaziri, a doctoral student in the Dus laboratory who led the work. Even more interesting is that the effect of gene silencing is in fact persistent so that even when animals are removed from the high sugar diet, the genes associated with taste are still altered and the animals still exhibit sweet taste defects. “

Fruit flies only have about 60 sweet tasting cells in their mouthparts. After purifying these taste cells from flies that had followed a controlled diet and 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 to RNA to synthesize proteins – from these 60 cells and sequencing the messenger RNAs associated with them 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 over 80% of the sweetness genes were silenced. This is because PRC2 changed its binding on DNA and in doing so changed the “program / software” that the taste cells were running. The new program didn’t make them respond as well to sweetness and almost reprogrammed their identity as sweet tasting 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 behaviors and food choices, similar to an early childhood trauma that leaves a lasting effect on the adult brain, “Vaziri says.

To confirm that PRC2 was the source of gene silencing, the researchers mutated the complex to see if they could restore normal gene expression in cells. By mutating the complex, they found that the fly had not suffered a decline in its ability to sense sweet flavors.

Interestingly, flies that could still taste sugar were also able to stay skinny. Flies that experienced a decrease in their ability to sense sweet tastes became obese. The reason why this happens lies in some of the Dus lab’s previous research on how sugar interferes with fullness signals. When flies’ ability to taste sugar is blunted, they eat more and more sugar to achieve the same levels of satiety. When their ability to taste sugar is not blunted, they finish their meals earlier.

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