title: A high-throughput assay for quantifying appetite and digestive dynamics.
abstract: Food intake and digestion are vital functions, and their dysregulation is fundamental for many human diseases. Current methods do not support their dynamic quantification on large scales in unrestrained vertebrates. Here, we combine an infrared macroscope with fluorescently labeled food to quantify feeding behavior and intestinal nutrient metabolism with high temporal resolution, sensitivity, and throughput in naturally behaving zebrafish larvae. Using this method and rate-based modeling, we demonstrate that zebrafish larvae match nutrient intake to their bodily demand and that larvae adjust their digestion rate, according to the ingested meal size. Such adaptive feedback mechanisms make this model system amenable to identify potential chemical modulators. As proof of concept, we demonstrate that nicotine, l-lysine, ghrelin, and insulin have analogous impact on food intake as in mammals. Consequently, the method presented here will promote large-scale translational research of food intake and digestive function in a naturally behaving vertebrate.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; and josuajordi@fas.harvard.edu.
authors.forename: Josua
authors.initials: J
authors.lastname: Jordi
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; and Committee for Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts.
authors.forename: Drago
authors.initials: D
authors.lastname: Guggiana-Nilo
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; and.
authors.forename: Edward
authors.initials: E
authors.lastname: Soucy
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; and.
authors.forename: Erin Yue
authors.initials: EY
authors.lastname: Song
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lei Wee
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; and.
authors.forename: Florian
authors.initials: F
authors.lastname: Engert
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001696:Biomechanical Phenomena; D004063:Digestion / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004867:Equipment Design; D005247:Feeding Behavior / Q000187:drug effects; D005456:Fluorescent Dyes / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000295:instrumentation; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000494:pharmacology; D007814:Larva; D008239:Lysine / Q000494:pharmacology; D023421:Models, Animal; D008954:Models, Biological; D009538:Nicotine / Q000494:pharmacology; D061848:Optical Imaging / Q000295:instrumentation; D013550:Swimming; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism / Q000502:physiology*
chemical_list: D005456:Fluorescent Dyes; D054439:Ghrelin; D007328:Insulin; D009538:Nicotine; D008239:Lysine
keywords: DiR' dye; appetite; hunger; satiation; satiety