An appetite for understanding appetite

I have a sweet tooth, and I will always choose any pastry over spinach salad. I also know that many readers will share this preference. However, I am also aware that an unbalanced diet, in quantity and quality, is associated with serious health problems, including type 2 diabetes, metabolic syndrome, cardiovascular diseases, and cancer. It has therefore become a pressing question in basic and translational neurobiology to understand both how animals choose what to eat and in what quantities. The feelings of hunger and satiety are thought to arise from crosstalk between the digestive system, the energy-storing cells (such as adipocytes), and ultimately, the brain. In an effort to understand the mechanisms that drive hunger, trigger satiety, and modulate appetite, scientists often turn to invertebrate model organisms. Invertebrates are easy to raise and to manipulate experimentally. Their reduced complexity allows a finer and quicker dissection of the cellular and molecular pathways controlling appetite. For example, while the human brain has 86 billion neurons, the brain of the vinegar fly Drosophila melanogaster contains about 250,000, and the nervous system of the nematode Caenorhabditis elegans is composed of only 302 neurons. Scale aside, the neurons, gut, and other tissues in these simpler organisms are very similar in form, function, and genetics to those of humans. In all animals, regardless of their size and complexity, health is promoted by the ingestion of appropriate quantities of specific nutrients, and these quantities are dictated by the internal nutritional state: too little or too much of a specific nutrient can be detrimental. Therefore, animals must execute precise control over the consumption of these nutrients. D. melanogaster obtains its proteins from the yeast that grows in rotting fruit, and yeast deprivation induces in the fly both a specific appetite for proteins and a reduction in the capacity to lay eggs. A recent study published in PLOS Biology investigated the factors that control this homeostatic appetite for proteins [1], finding that both dietary essential amino acids (those that the animals cannot synthetize themselves and so need to be obtained from food) and the bacteria that live in the gut of flies are key modulators of the appetite for proteins. The authors first observed that the behavioral and physiological effects of a diet poor in protein could be reproduced by removing from the diet only the essential amino acids. Furthermore, if the authors transformed a non-essential amino acid into an essential amino acid (by genetically disrupting the flies’ ability to make it), its removal from the diet induced the same increase in appetite for proteinaceous food as the removal of any of the original essential amino acids. Intriguingly, however, flies with an appropriate gut microbiome did not develop this appetite for proteins when fed a diet low in amino acids, and only partially reduced the number of eggs they laid. Specifically, two gut bacteria species, Acetobacter pomorum and Lactobacillus sp., when introduced with an otherwise amino acid-poor diet, suppressed the physiological and behavioral changes. However, neither bacterium could do it alone, which made the authors conclude that they must be working together.