Deciding how much to eat is a complicated process, involving how much energy we have stored, what food was available before, how healthy the food is and what we remember about all these things. When food is scarce, our bodies efficiently store energy for survival, but how animal's brains manage the delicate balance between how much they consume and their energy stores is not clear. Like us, fruit flies, Drosophila melanogaster, convert food into glucose for energy and store the extra as glycogen. Flies monitor their energy levels using insulin-like hormones that inform their brains about stored glycogen. These hormones influence a group of neurons responsible for assessing the pleasure derived from food, by releasing a chemical messenger called octopamine in the brain. Mutant flies that do not make octopamine eat less sugar, live longer and struggle with taste and learning, but their memory of sugary food improves over time. Henrike Scholz and colleagues from the University Köln, Germany, were curious to understand octopamine's role in combining information about energy reserves, food quality, evaluation of different food types and related memory formation in fruit flies.
To assess the impact of internal energy stores on food-related memories, the researchers trained fruit flies to associate a smell with a sugar reward, to find out how starvation affected the insects’ memories. When flies were starved for 16 h before training, they formed short-term memories of the smell's association with sugar that lasted up to 3 h; however, flies that were starved for 40 h formed longer lasting memories (∼24 h). Mutant flies that were unable to produce octopamine formed a much more stable form of memory. These findings suggest that being hungry affects how well memories last over time. Longer periods without food result in longer lasting memories, even in flies that don't make octopamine.
The team then checked whether hunger affects what foods flies choose. When the normal (control) and octopamine-deficient mutant flies were starved, their glycogen levels decreased over time. However, the mutant flies initially had higher glycogen levels than the controls and even after 40 h without food, their glycogen levels remained comparatively high. The scientists then tested whether hunger affected the food preferences of the flies by offering them different foods. The octopamine-deficient flies were not as interested in sugary food after short periods of starvation, but overate after longer periods of starvation, despite still having energy stores. This suggests that their liking for sugary food changes based on their energy levels.
How does the condition of the body's energy stores help the flies to remember the pleasurable sensations that they feel when they consume sugar to regulate their food intake? Insulin-like hormone signals control how much glycogen is stored in the body. So the team was curious to see whether blocking insulin might influence the brain's reward system, which is signalled by octopamine. They found that mutant flies lacking octopamine that had large energy reserves had reduced short-term memory of food, because the insulin receptor integrates information about their energy reserves with how rewarding the food is to eat. Scholz and her team also discovered that blocking the insulin receptor signalling in reward neurons when the flies had large energy reserves resulted in a positive memory of the food, even though the flies had plentiful energy reserves. In other words, well-fed flies with large energy stores found food pleasurable thanks to octopamine signalling, when they could no longer sense their internal energy reserves as a result of the loss of insulin signalling, leaving them at risk of overeating.
Scholz and colleagues’ study sheds light on how octopamine affects food memory in flies and how energy levels influence their reactions to food rewards, and helps to explain why some animals overeat, despite having large energy reserves, thanks to disruption of insulin signalling.
