How the Brain Controls Food Intake
In healthy humans, food intake is strictly regulated by sensory, homeostatic, and hedonic neural circuits, which balance energy intake with energy expenditure. Failure to regulate food perception and appetite result in maladaptive eating behaviors and an increase in the occurrence of metabolic syndromes and eating disorders. While neural circuits that regulate food intake have been extensively investigated in rodent models, the complexity of the mammalian brain makes it challenging to explain the underlying molecular mechanisms and circuit dynamics controlling food intake.
Nilay Yapici, Neurobiology and Behavior, is using a genetic model organism, the fly (Drosophila melanogaster), to understand the fundamental principles of how the brain integrates the sensory percept of food with the sensation of hunger to regulate food intake on the level of molecules, cells, and circuits. Flies are an excellent model to investigate these processes because they have 1000-fold fewer neurons in the brain than mice, and yet they still show hunger states and specific food intake control remarkably similar to those in vertebrates.
Yapici has previously shown that flies, like humans, regulate their food intake by integrating the taste and nutrient value of food with hunger sensation in the nervous system. She identified a novel class of excitatory interneurons (IN1) in the fly brain that regulate food ingestion.
In this project, she is further identifying the IN1 food intake circuitry, using optogenetics and anterograde trans-synaptic circuit tracing; revealing how IN1 neurons and downstream circuitry change activity during food search in a virtual reality foraging assay, using two-photon microscopy; and capturing the activity of IN1 neurons chronically in an intact fly as flies are being food deprived, using cutting-edge three-photon technology. In parallel with the food intake circuit dissection efforts, Yapici is anatomically and functionally dissecting the role of genes that fail to show compensatory feeding after 24 hours of food deprivation.
The research aims to yield exciting new insights to how the brain controls food intake, and to reveal shared genetic substrates and circuit principles that can inform therapeutic strategies for obesity and eating disorders.
NIH Award Number: 1R35GM133698-01