Behavioral dissection of hunger states in Drosophila.

Hunger is a motivational drive that promotes feeding, and it can be generated by the physiological need to consume nutrients as well as the hedonic properties of food. Brain circuits and mechanisms that regulate feeding have been described, but which of these contribute to the generation of motive forces that drive feeding is unclear. Here, we describe our first efforts at behaviorally and neuronally distinguishing hedonic from homeostatic hunger states in Drosophila melanogaster and propose that this system can be used as a model to dissect the molecular mechanisms that underlie feeding motivation. We visually identify and quantify behaviors exhibited by hungry flies and find that increased feeding duration is a behavioral signature of hedonic feeding motivation. Using a genetically encoded marker of neuronal activity, we find that the mushroom body (MB) lobes are activated by hedonic food environments, and we use optogenetic inhibition to implicate a dopaminergic neuron cluster (protocerebral anterior medial [PAM]) to α'/ß' MB circuit in hedonic feeding motivation. The identification of discrete hunger states in flies and the development of behavioral assays to measure them offers a framework to begin dissecting the molecular and circuit mechanisms that generate motivational states in the brain.

Drosophila serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice.

It has been recognized for nearly a century that diet modulates aging. Despite early experiments suggesting that reduced caloric intake augmented lifespan, accumulating evidence indicates that other characteristics of the diet may be equally or more influential in modulating aging. We demonstrate that behavior, metabolism, and lifespan in Drosophila are affected by whether flies are provided a choice of different nutrients or a single, complete medium, largely independent of the amount of nutrients that are consumed. Meal choice elicits a rapid metabolic reprogramming that indicates a potentiation of TCA cycle and amino acid metabolism, which requires serotonin 2A receptor. Knockdown of glutamate dehydrogenase, a key TCA pathway component, abrogates the effect of dietary choice on lifespan. Our results reveal a mechanism of aging that applies in natural conditions, including our own, in which organisms continuously perceive and evaluate nutrient availability to promote fitness and well-being.

The foods we eat can affect our lifespan, but it is also possible that thinking about food may have effects on our health. Choosing what to eat is one of the main ways we think about food, and most animals, including the fruit fly Drosophila melanogaster, choose their foods. The effects of these choices can affect health via a chemical in the brain called serotonin. This chemical interacts with proteins called serotonin 2A receptors in the brain, which then likely primes the body to process nutrients. To understand how serotonin affected the lifespan and health of fruit flies, Lyu et al. compared flies that were offered a single food to those that could choose between several foods. The flies that had a choice of foods lived shorter lives and produced more serotonin, but these effects were reversed when Lyu et al. limited the amount of a protein called glutamate dehydrogenase, which helps cells process nutrients. These results suggest that choosing what we eat can impact lifespan, ageing and health. Human and fly brains share many similarities, but human brain chemistry is more complex, as is our experience of food. This work demonstrates that food choices can affect lifespan. More research into this phenomenon may shed further light onto how our thoughts and decision-making impact our health.