April 13, 2021
Written by: Marissa Maroni
Imagine you are walking down the street one day and come across a group of girl scouts selling cookies. You buy boxes of Thin Mints and Samoas then proceed to bring them back to your house. You make a mental note that you will save some for later and decide to have a cookie…maybe two…or the whole box (good thing you got two boxes!). Later, you look back at the empty box, surprised, and question, “How did I even eat them all?” Take comfort in the fact that you are not alone in this experience. Sweet foods are hard to resist! But what could be causing this high consumption of sugary foods? Previous research has shown that high sugar diets can alter taste perception, for example by making sweet foods taste less sweet. This change in taste perception can lead to greater food intake causing weight gain, obesity, and metabolic disease. A recent study uncovered that epigenetics, or reversible changes made to our genetic code, plays a role in the changing of taste perception caused by a high sugar diet.
What is epigenetics?
Many high school biology classes will discuss how DNA is made up of thousands of genes that create each unique person. The set of mutations in the DNA sequence permanently alters a person’s genetic code. Epigenetics means “above genes” and differs from genetics in the fact that it leads to reversible changes in DNA, often caused by the environment. Genes can be turned “on” and “off” by epigenetic regulator proteins. These proteins can control when and how much of a gene is expressed. If you want to learn more about epigenetics in general check out this previous PennNeuroKnow article or this video. The experiments discussed in this article specifically investigate one group of epigenetic regulator proteins called the Poly Comb Repressive complex 2.1 (PRC2.1). PRC2.1 plays important roles in development, stem cell biology, and cancer, among many other functions1. PRC2.1 maintains genes in active or inactive states meaning that it can influence which genes are on or off. You can imagine PRC2.1 as a manager of your DNA commanding certain genes to turn on and off.
What did the researchers find?
Flies as a model system
Scientists from the University of Michigan were interested in sweet taste perception. They asked, “what changes could be occurring at the genetic level that cause changes in sweet taste perception?” To begin answering this question, researchers needed a model organism – an animal that is widely used by scientists when experiments in humans are not possible. The fly model provides a wide range of genetic tools that scientist can harness to ask specific questions about how genetics influence behavior. Although most would not consider pesky flies similar to humans, 65% of genes that have roles in human disorders are either identical or very similar to fly genes2. Therefore, by studying taste in this model organism, researchers can draw conclusions about human taste.
How can you measure sweet taste perception?
Unlike humans, flies have an organ called the proboscis that is used to taste and eat. Normally, flies will extend their proboscis more in response to a higher concentration of sugar. Researchers measured sweet taste perception by recording the number of proboscis extensions in response to different concentrations of sugar (figure 1). The more a fly extends its proboscis, the more likely it is to be experiencing a sweet taste. Previously, these researchers found that flies fed a high sugar diet would not extend their proboscis as much in medium and low sugar concentrations. This suggests that flies that were used to a high sugar diet did not find these lower sugar concentrations as satisfying. Further, these flies with a high sugar diet had reduced activity in their taste neurons, increased food intake, and developed obesity, measured by a higher fat to protein ratio3,4. Overall, this suggested that a high sugar diet can change how you taste and ultimately lead to downstream effects such as weight gain. This model of changes in sweet taste perception provided researchers with a simple system to test how these changes occur at a genetic level.
PCR2.1 plays a role in changing sweet taste perception
The researchers first wanted to identify what could be causing these changes in sweet taste perception in flies given a high sugar diet5. One advantage of the fly model system is that it is relatively simple to conduct large genetic screens. In genetic screens, mutant flies are generated and tested to see if the flies have a phenotype, or observable characteristic, of interest. Once that phenotype is observed, the mutations that caused that phenotype can be identified, leading scientists to the genes that are normally responsible for a certain behavior.
In the case of this study, researchers were interested in finding a mutant fly strain that did not have a dulled sweet taste perception when fed a high sugar diet. This genetic screen led researchers to the previously mentioned group of epigenetic regulator proteins called PRC2.1 as flies with mutations in PRC2.1 did not have dulled sweet taste perception (i.e., they continued to extend their proboscis at the same rates) when given a high sugar diet. Using genetic techniques, researcher depleted one of the PRC2.1 proteins in only neurons that respond to sweet tastes and found, once again, that the sweet taste perception was not changed in the high sugar diet fed flies with this mutation. Interestingly, when PRC2.1 mutant flies consumed a high sugar diet, they did not experience diet-induced obesity. Together, these results suggest that PRC2.1 plays a role in blunting sweet taste perception in flies fed a high sugar diet.
PRC2.1 reduces neuronal activity in sweet taste neurons
Previously, it was found that sweet taste neurons have reduced activity in response to sugar in the high sugar diet flies. Researchers hypothesized that PRC2.1 could be responsible for these changes in neuronal activity in sweet taste neurons. When PRC2.1 was mutated, the neural responses in sweet sensing neurons were not reduced in high sugar diet flies in comparison to control diet flies. This suggests that PRC2.1 is normally involved in this reduced response in sweet taste neurons. Since PRC2.1 is an epigenetic regulator, the researchers wanted to understand what genes in the DNA this complex could be managing that are causing the altered sweet taste perception. There were 5 genes identified that each control different aspects of sensory neuron physiology. In sum, PRC2.1 blunts sweet taste perception by changing the expression of genes important for sweet taste neuronal function.
PRC2.1 causes lasting changes in sweet taste perception
Thus far, researchers had found that the epigenetic regulating complex PRC2.1 reduces neuronal activity in sweet tasting neurons by changing the expression of genes that regulate sensory neuron function. The remaining questions were, “Is this epigenetic change lasting? If flies are returned to a control diet, will their sweet taste perception return back to normal?” To test this, researchers returned high sugar diet flies back to a control diet for up to 20 days. They found that even after returning flies to a control diet, flies still had altered sweet taste perception. The altered perception lasted even though their fat stores returned to levels that were comparable to controls. Further when PRC2.1 was inhibited in these recovering flies, their sweet taste was restored back to normal. Together, these findings demonstrate that the lasting changes in sweet taste perception are caused by PRC2.1.
Overall, this study is an example of how your environment can cause lasting changes to your body, even if these changes do not permanently mutate your genes. The next time you eat a box of cookies cut yourself a break. You may have altered taste perception making it harder to put that box down!
Image Credits:
Photo by Sharon McCutcheon on Unsplash
References:
1. Sauvageau, M., & Sauvageau, G. (2010). Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. Cell stem cell, 7(3), 299-313.
2. Ugur, B., Chen, K., & Bellen, H. J. (2016). Drosophila tools and assays for the study of human diseases. Disease models & mechanisms, 9(3), 235-244.
3. May, C. E., Vaziri, A., Lin, Y. Q., Grushko, O., Khabiri, M., Wang, Q. P., … & Dus, M. (2019). High dietary sugar reshapes sweet taste to promote feeding behavior in Drosophila melanogaster. Cell reports, 27(6), 1675-1685.
4. May, C. E., Rosander, J., Gottfried, J., Dennis, E., & Dus, M. (2020). Dietary sugar inhibits satiation by decreasing the central processing of sweet taste. Elife, 9, e54530.
5. Vaziri, A., Khabiri, M., Genaw, B. T., May, C. E., Freddolino, P. L., & Dus, M. (2020). Persistent epigenetic reprogramming of sweet taste by diet. Science advances, 6(46), eabc8492.
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