Fly on the Wall

Making fly science approachable for everyone

Tag: feeding

Breaking Research: Bitter substances suppress sweet signaling in the brain

Imagine you’re a fly buzzing through the forest looking for something to eat, and you happen upon a sweet fruit that tastes bitter. What’s a fly to do? A sweet fruit is a nutritious meal, but the bitter taste implies toxins. In a recent paper by French et al. in the Journal of Neuroscience, researchers discovered that bitter substances can block sugar signaling in the brain to prevent flies from making questionable meal choices such as these.

The brain deals with these sorts of ambiguities every day. After all, very few foods have a single taste modality of sweet, bitter, sour, salty, or umami (savory/meaty). Instead, most foods are a combination of several of these tastes. But while sweet, umami, and sometimes salt flavors can indicate nutrition, sour and bitter often serve as a warning signals for acidity or toxins, respectively. So how does the brain decide what’s safe to eat when it encounters a meal that’s both sweet and bitter?

fly drinkingFruit flies taste and eat with their proboscis. Click here or on the image to see a video of a fruit fly eating!

To answer this question, French et al. turned to fruit flies. Like the rest of us in the animal kingdom, flies are attracted to sweet foods and avoid bitter foods, and they have taste cells in their proboscis (the fly tongue, see image). Over the past decade, fly researchers have developed quick and easy experiments to test food preferences in flies, and have even mapped the neurons corresponding to each taste modality on their proboscis, including bitter-sensing cells and sweet-sensing cells. This provided a great system to investigate how the brain decides to avoid sweet foods with a bitter aftertaste.

In flies and other animals, bitter foods activate bitter-sensing cells that cause aversion, and sweet foods activate sweet-sensing cells that cause attraction and feeding. Yet, researchers in multiple animal models had found that the presence of a bitter substance in a sweet food can suppress the eating behavior, indicating some crossover between how these flavors are represented in the brain. While this seems straightforward (you don’t want to eat something potentially deadly, even if it’s nutritious), exactly how and why the brain makes this decision was not understood. Are bitter-sensing cells suppressing sweet-sensing cells? Or do the bitter substances instead inhibit the sweet-sensing cells directly?

Interestingly, the authors of this paper discovered that bitter substances could actually inhibit the sweet-sensing cells directly. The researchers first confirmed that flies were attracted to sugar water (extending their proboscis toward it, see image), and avoided water with a bitter chemical (retracting their proboscis away from it). The authors then mixed a bitter substance into the sugar water and found that the flies quickly recoiled from the meal.

The authors hypothesized that if bitter-sensing cells themselves were suppressing sweet-sensing cell activation, then killing off the bitter-sensing cells should prevent the flies from avoiding the sugar+bitter offering. But instead, they found that the flies were still able to avoid sugar mixtures with certain bitter substances. They further investigated by recording the electrical activity of the taste neurons and found that some of the bitter substances they tested were actually interacting directly with the sweet-sensing cells to suppress their activity. This was a surprising finding, since it was previously thought that sweet-sensing cells only respond to sweet substances, bitter-sensing cells only respond to bitter, and so on.

So if bitter substances can directly suppress sugar-sensing and therefore prevent eating, why do bitter-sensing cells even need to exist? What’s the evolutionary advantage? For one, bitter chemicals may show up in other non-sweet foods that flies will need to recognize as dangerous. But even more interestingly, the researchers found that not all bitter substances could directly suppress sweet-sensing cells. For example, strychnine (a deadly pesticide) and three other bitter chemicals interacted with sweet-sensing cells, but caffeine, nicotine, and a few other bitter chemicals did not. The researchers suggest that the first group of chemicals may be much more toxic to the flies, and they therefore may have evolved a back-up system of protection from them. Thus, bitter-sensing cells are still necessary for signaling avoidance of less-toxic but still-dangerous chemicals.

fly drinkingChocolate is an example of a food with conflicting signals. Theobromine, the bitter (and stimulating) chemical in chocolate, is safe in small quantities but can be dangerous in large quantities. Yet most people love the taste of chocolate. Have we evolved to recognize that the potential nutritional benefits of chocolate outweigh the risk?

This research shows that flies have developed two methods of detecting dangerous bitter substances in potential food sources. First, bitter-sensing cells are activated and signal aversion. Second, sweet-sensing cells are directly suppressed by some bitter chemicals in order to simplify the taste messages sent to the brain, which would otherwise be conflicting. Research in other animal models, including mammals, has found that they also avoid sweet foods laced with bitter chemicals, suggesting that these organisms likely use similar strategies for deciding what’s safe to eat.

So that leaves me with one remaining question: Why does chocolate taste so good?




  • French AS, Sellier MJ, Moutaz AA, Guigue A, Chabaud MA, Reeb PD, Mitra A, Grau Y, Soustelle L, & Marion-Poll F (2015). Dual mechanism for bitter avoidance in Drosophila. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35 (9), 3990-4004 PMID: 25740527

Thanksgiving Special: Uncovering the link between sleep and food

rest and digest turkey

If you ate a big Thanksgiving dinner yesterday, you probably felt drowsy and sluggish afterward, a phenomenon often referred to as a “food coma”. The belief that it’s caused by the tryptophan in turkey is a long busted myth, and in fact it can happen after any carb-heavy meal. The reasons for this post-food slump are relatively well understood from experiments in humans and other mammals. For one, big meals trigger a “rest and digest” response when the food reaches the stomach and small intestine (via activation of the parasympathetic nervous system). This diverts energy to digestion, making you feel sluggish and sleepy.  But wait, there’s more! Eating a meal full of carbs and other sugars also stimulates the release of insulin, which triggers a process to take up nutrients from the bloodstream. But a side effect of this process is an increase in the amount of serotonin and melatonin in the brain, two chemicals that are associated with drowsiness (and often happiness).

So having a full stomach makes you sleepy, but did you know that the relationship between sleep and food goes deeper than that? For example, studies in animals from fruit flies all the way to humans have shown that having an empty stomach can keep you awake. Even worse, chronic sleep deprivation stimulates appetite and can lead to weight gain. Studies in humans have uncovered strong correlations between sleep disorders like insomnia and obesity-related disorders such as diabetes and cardiovascular disease. One of the reasons for this is that sleep loss wreaks havoc on the levels of certain hormones, such as the “hunger hormone” ghrelin.

Thus, even though sleeping and eating are mutually exclusive behaviors (you can’t sleep while you’re eating), they’re also obviously connected. Both are essential for survival, so the brain may often be promoting at least one of them. But how does the brain decide which behavior is more important at any given time? When you’re hungry, it seems more important to stay awake and find food to prevent starvation, but sleep deprivation also has health consequences, so the brain needs to ensure you get enough sleep.

So how are sleep and hunger connected in the brain? Are they independent, so that hunger suppresses sleep, and sleepiness stimulates hunger? Or maybe they arise from the same mechanism, which signals in turn for either sleep or eating depending on your body’s needs. Answering this question will improve our understanding of sleep- and obesity-related disorders and how they’re linked, a necessary step before treatments can be developed.

Fruit flies make a great animal model for answering detailed questions like these, which take place on a molecular and cellular scale. Although much research has yet to be done, there have already been some informative findings. For starters, scientists have found that insulin-producing cells in the fly brain regulate both feeding and sleep, providing a cellular link between these two behaviors (remember that insulin’s activities are partially responsible for the food coma after Thanksgiving dinner). Their findings suggest that these cells integrate information from other brain regions about sleep need and hunger, and may even potentially act as a “behavioral switch” to signal which behavior is more important at any given time.

Other fruit fly researchers have found a link between eating and sleeping in a single molecule called “NPY-like short neuropeptide F” (sNPF). sNPF had already been shown to regulate food intake, but recently it was found that sNPF also promotes sleep. sNPF is similar to a mammalian chemical called “neuropeptide Y” (NPY), which also plays a little-understood role in sleep and eating in mammals. NPY has recently been studied as a possible drug target for obesity treatment in humans even though its role in other behaviors is unclear, so a better understanding of this chemical is essential to account for possible side effects such as sleep disruption.

Research in a variety of animal models (and humans) has shown us that sleep and hunger are related. Overall, the combined results of fruit fly research suggests that sleep and feeding behaviors may arise from shared mechanisms in the brain. Future studies will pin down the exact mechanisms and apply those findings to more complex mammalian systems. Hopefully, this research will lead to the development of drugs that can help with sleep- and obesity-related disorders. In the meantime, I think I’ll try drinking coffee with Thanksgiving dinner.

Happy Thanksgiving!


© 2019 Fly on the Wall

Theme by Anders NorenUp ↑

Protected by Akismet
Blog with WordPress

Welcome Guest | Login (Brandeis Members Only)