A high-throughput assay for quantifying appetite and digestive dynamics

Abstract

Jordi J, Guggiana-Nilo D, Soucy E, Song EY, Wee CL, Engert F. A high-throughput assay for quantifying appetite and digestive dynamics. Am J Physiol Regul Integr Comp Physiol 309: R345-R357, 2015. First published June 24, 2015 doi:10.1152/ajpregu.00225.2015.-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.appetite; hunger; satiation; satiety; DiR' dye FOOD INTAKE AND DIGESTION are key physiological processes that provide nutrients to drive all bodily functions. Nutrient intake is matched to nutritional needs by the brain-a process termed nutrient homeostasis-using an intertwined organism-wide array of extrinsic and intrinsic cues coding food availability and demand (2, 42). Dysfunction of feeding and digestive behavior is at the root of global health problems, such as obesity, malnutrition, and Type 2 diabetes, among many others, and, therefore, a deeper understanding of feeding and digestive behavior is of high importance (25).Drugs or genetic manipulations that alter food intake or digestion are highly desirable remedies for food-related disorders. To screen for genes or small molecules with clinically desirable impact, the technology of choice needs to support the analyses of hundreds to thousands of individual animals. Until now, large-scale studies of feeding behavior have solely been feasible in small invertebrates such as Drosophila, but were constrained to 20 -50 conditions in vertebrates, thereby making large-scale screens elusive (12,17,35). Technically, even more demanding than measuring food intake is the quantification of nutrient digestion, as there is no direct optical access to the gastrointestinal tract in most species. More specialized technologies, such as bioluminescence, MRI, or computed tomography, have been valuable to generate insights into in vivo dynamics of digestive function (10,18,19,31). However, all of these methods require immobilization of the experimental subject to reduce motion artifacts, thereby making concurrent behavioral observations impossible. Consequently, quantifying the dy...

Inadequate food intake at high temperatures is related to depressed mitochondrial respiratory capacity

“…Lower hepatic ATP levels are associated with a stimulation in feeding behaviour (Rawson and Friedman, 1994;Rawson et al, 1996). Since feeding behaviour is regulated in fish in a very similar manner to that in mammals (Jordi et al, 2015;Lin et al, 2000), it is unclear why the brown trout with the lowest food intake in this study did not increase their intake when they clearly had the need to do so and had access to ad libitum food. One possible explanation for this is that locomotion and digestive activity require a substantial amount of energy as they involve ATP-dependent processes.…”

“…lower RCR) within the intestine could have contributed to the low food intake, because this would have resulted in limited production of ATP for nutrient absorption, nutrient transport and protein synthesis (Pelletier et al, 1994). Since the digestive track is involved in the central regulation of food intake (Jordi et al, 2015;Lin et al, 2000), the low food intake may also reflect a more general drop in intestinal function (Eya et al, 2012), but this requires further study. The mitochondrial respiration rate of aquatic ectotherms is known to vary with temperature in vitro (Pörtner et al, 1999) and changes in water temperature can induce adjustments in mitochondrial respiratory capacities in fish (Chung and Schulte, 2015;Fangue et al, 2009;Iftikar and Hickey, 2013;Iftikar et al, 2014).…”

Role of branchiomotor neurons in controlling food intake of zebrafish larvae

“…Further, due to the central role of the hypothalamus in altering food intake by regulating appetite and satiety in mammals, the relatively simple organization of the hypothalamic axis in juvenile (larval) and adult zebrafish provides a good model to investigate underlying structural and physiological mechanisms (Cassar et al, 2015; Clift et al, 2014; Farber et al, 2001; Filosa et al, 2016; Jordi et al, 2015; Minchin et al, 2013; Piccinetti et al, 2010; Shimada et al, 2012; Volkoff et al, 2005; Yokobori et al, 2012). However, the motor circuits that drive food intake have received little attention.…”

Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics

“…Activity monitoring can also be used to measure circadian rhythms and habituation [77]. Even food seeking and digestive physiology can be directly measured [81]. Food-seeking, tantrums, and skin-picking are all problematic PWS-associated behaviors for which no effective drug treatment has been routinely helpful.…”