Anorexigenic factors

Cholecystokinin (CCK)
In mammals, CCK inhibits food intake and induces the release of digestive enzymes from intestine/pancreas and gallbladder (Boguszewski et al., 2010; Dockray, 2012).
In fish, CCK was first shown to have a role in digestion, as, for example, it stimulated contraction of the gallbadder in coho (Vigna and Gorbman, 1977) and Atlantic (Aldman and Holmgren, 1987) salmon, as well as bluegill (Lepomis macrochirus), killifish (Fundulus heteroclitus), and the holostean bowfin (Amia calva) (Rajjo et al., 1988), stimulated lipase secretion in the stomachless killifish (Honkanen et al., 1988) and inhibited gastric secretion in Atlantic cod (Holstein, 1982). The first direct evidence of the actions of CCK on feeding was provided by injections in goldfish (Himick and Peter, 1994), followed by cloning of goldfish CCK cDNA (Peyon et al., 1998) and the demonstration of periprandial variations in CCK mRNA expression levels (Peyon et al., 1999). Subsequently, a number of studies have characterized CCK in several fish, including other Cypriniformes (e.g., common carp Zhong et al., 2013; zebrafish Koven and Schulte, 2012; Tian et al., 2015; grass carp; blunt snout bream Ping et al., 2013; Ji et al., 2015), Characiformes (e.g., cavefish Wall and Volkoff, 2013, dourado Pereira et al., 2015; Volkoff et al., 2016, thin dogfish Oligosarcus hepsetus Vieira-Lopes et al., 2013, pirapitinga Volkoff, 2015a, red-bellied piranha Volkoff, 2014a, pacu Volkoff et al., 2017), Salmoniformes (e.g., Atlantic salmon Valen et al., 2011), Gadiformes (Atlantic cod Tillner et al., 2013), Perciformes [e.g., yellowtail (Furutani et al., 2013; Hosomi et al., 2014); Astatotilapia burtoni (Grone et al., 2012); cunner (Babichuk and Volkoff, 2013; Hayes and Volkoff, 2014); sea bass (Tillner et al., 2014); yellow croaker (Larimichthys crocea) (Cai et al., 2015); white sea bream, Diplodus sargus (Micale et al., 2012, 2014)], Pleuronectiformes (e.g., winter flounder (MacDonald and Volkoff, 2009a), Atlantic halibut Kamisaka et al., 2001, olive flounder Kurokawa et al., 2000) and Siluriformes (channel catfish Peterson et al., 2012).
Overall, in all fish species studied to date, CCK appears to have similar roles in feeding and digestive processes to its role in mammals, i.e., it acts as a satiety/appetite-inhibiting factor and induces the release of digestive enzymes from the GIT.

Leptin
Leptin, a peptide originally cloned in obese ob/ob mice (Zhang et al., 1994), is secreted in mammals mainly by white adipose tissue, and its blood levels are proportional to body fat content (Park and Ahima, 2015). Leptin is a multifunctional hormone in both mammals (Park and Ahima, 2015) and fish (see review by Gorissen and Flik, 2014) and is involved in the regulation of not only food intake and body weight, but also reproduction, development and stress responses.
First hints of a role of leptin in fish were provided by reports of a decrease in feeding in goldfish ICV-injected with human leptin (Volkoff et al., 2003). The first fish leptin was identified in the pufferfish genome in 2005 by synteny studies (Kurokawa et al., 2005), followed by isolation of zebrafish, medaka, and carp leptins (Huising et al., 2006b). Since then, leptins have been identified in several fish species and shown to have multiple physiological functions (reviewed in Copeland et al., 2011; Angotzi et al., 2013; Londraville et al., 2014). As opposed to mammals who have a single leptin gene, several fish species have several leptin gene paralogs (e.g., lepA and lepB). Also in contrast to mammals, where subcutaneous fat is the main source of leptin, fish leptin is expressed in several tissues including liver and intestine, which is consistent with the fact that fish generally store lipids in intra-abdominal regions and liver (Birsoy et al., 2013).
Most studies on fish leptin have been conducted in Cypriniformes, in particular goldfish and zebrafish, and Salmoniformes. In goldfish, leptin injections decrease feeding and locomotor behavior (Volkoff et al., 2003; de Pedro et al., 2006; Vivas et al., 2011; Tinoco et al., 2012) in part by stimulating anorexigenic sytems (e.g., CART, CCK, and POMC) and inhibiting orexigenic ones (e.g., orexin, NPY, AgRP) (Volkoff et al., 2003; Yan et al., 2016). Similarly, in rainbow trout (Salmoniforme), central leptin administration suppresses food intake and increases the hypothalamic expressions of CART and POMC (Gong et al., 2016). Leptin treatment also inhibits feeding in grass carp (Li et al., 2010) (Cypriniforme) and increases energy expenditure in zebrafish larvae (Renquist et al., 2013). In Atlantic salmon (Salmoniforme), chronic IP treatment with leptin induces a decrease in growth rates (Murashita et al., 2011), and in hybrid striped bass (Morone saxatilis × Morone chrysops) (Perciforme), leptin treatment increases hepatic IGF-1 mRNA expression (Won et al., 2016), suggesting that leptin affects metabolism and growth.
Hepatic/gut/brain leptin increases in expressions are seen post-prandially in goldfish (Tinoco et al., 2012, 2014b), common carp (Huising et al., 2006a) and zebrafish (Tian et al., 2015) (Cypriniformes) as well as pacu (Volkoff et al., 2017) (Characiforme). However, in rainbow trout plasma leptin levels decrease post-feeding (Johansson and Björnsson, 2015).
There is a great variability in results with regards to fasting-induced changes in the leptin system. In goldfish, no significant differences in either brain or liver leptin expressions are seen between control, overfed and fasting fish, suggesting nutritional status does not affect the leptin system in goldfish (Tinoco et al., 2012). Similarly, leptin expression is not affected by fasting in the liver of common carp (Huising et al., 2006a) (Cyrpiniforme) and Nile tilapia (Shpilman et al., 2014) (Perciforme) or in the brains of red-bellied piranha (Volkoff, 2015b) and pacu (Volkoff et al., 2017) (Characiformes). However, fasting/food restriction increases hepatic leptin expression in white-clouds mountain minnow (Tanichthys albonubes, Cypriniforme; Chen et al., 2016b), in most Perciformes examined (orange-spotted grouper Zhang et al., 2013, mandarin fish Yuan et al., 2016, and mackerel Scomber japonicus Ohga et al., 2015, European sea bass Gambardella et al., 2012), in Arctic charr (Jørgensen et al., 2013) and Atlantic salmon (Rønnestad et al., 2010; Trombley et al., 2012; Moen and Finn, 2013) (Salmoniformes). In contrast, decreases in leptin expression are seen in liver of zebrafish (lepA) (Gorissen et al., 2009) and striped bass (Morone saxatilis) (lepB, perciforme) (Won et al., 2012) and intestine of red-bellied piranha (Volkoff, 2015b), and in blunt snout bream (Cypriniforme), higher feeding rates are associated with increased leptin pituitary expression (Xu et al., 2016). Whereas plasma leptin levels increase following fasting in rainbow trout (Salmeron et al., 2015; Johansson et al., 2016; Pfundt et al., 2016), Atlantic salmon (Trombley et al., 2012) and fine flounder Paralichthys adspersus (Pleuronectiforme) (Fuentes et al., 2012, 2013), they have been shown to decrease in earlier studies in fasted burbot (Lota lota) (Gadiforme) (Nieminen et al., 2003) and green sunfish (Lepomis cyanellus) (Perciforme) (Johnson et al., 2000).
In fish, leptin has been linked to metabolism. For example, in zebrafish, knocking down lepA decreases metabolic rate (Dalman et al., 2013) and in golden pompano, Trachinotus blochii (Perciforme), lepA gene polymorphisms are associated with different body weights, heights and lengths (Wu et al., 2016). Whereas in mammals, leptin acts as an adipostat and its plasma levels are proportional to the amount of body fat, there is little evidence for such a role in fish. In topmouth culter Culter alburnus (Cyprinoforme), leptin mRNA expression is lower in wild populations, who have more muscle fat content than cultured fish (Wang et al., 2013), in grass carp, fish fed high fat diets have higher leptin expression (Li A. et al., 2016) than control fish, and in medaka, leptin receptor null-mutants have higher food intake and larger deposits of visceral fat than that of wild-type fish (Chisada et al., 2014), suggesting a correlation between leptin levels and fat. However, results from other studies seem to contradict this hypothesis: leptin receptor null adult zebrafish do not exhibit increased feeding or adiposity (Michel et al., 2016); In rainbow trout, leptin levels are higher in lean fish than fat fish (Salmeron et al., 2015; Johansson et al., 2016; Pfundt et al., 2016), and in Arctic charr, neither hepatic leptin expression nor plasma leptin levels correlate with fish adiposity (Froiland et al., 2012; Jørgensen et al., 2013); In murray cod Maccullochella peelii peelii (Perciforme), fish fed different experimental diets containing fish oil with or without vegetable oil have similar leptin levels (Ettore et al., 2012; Varricchio et al., 2012); In yellow catfish (Siluriforme), IP injections of human leptin reduce hepatic lipid content and the activities of lipogenic enzymes (Song et al., 2015) but Zn deficiency, which tends to increase hepatic and muscle lipid contents, does not affect leptin mRNA levels (Zheng et al., 2015).
Zebrafish lacking a functional leptin receptor have alterations in insulin and glucose levels, suggesting a role of leptin in the control of glucose homeostasis (Michel et al., 2016), which is consistent with data showing that leptin gene expression is induced by glucose in grass carp (Lu et al., 2015) and that leptin injections increase plasma glucose levels in Nile tilapia (Baltzegar et al., 2014).
Interestingly, in the Gymnotiforme Eigenmannia virescens, intramuscular injections of leptin increase electric organ discharges (EOD) amplitude in food-deprived but not well-fed fish, suggesting that leptin mediates EOD responses to metabolic stress in electric fish (Sinnett and Markham, 2015).
Overall, there seems to be a great species-specific variability in the functions of leptin with regards to the regulation of feeding and metabolism in fish, perhaps due to different lipid metabolism and storage areas among fish species.

Peptide YY
Peptide YY consists of two forms, PYYa and PYYb (previously called PY) (Wahlestedt and Reis, 1993; Cerdá-Reverter and Larhammar, 2000; Sundström et al., 2013) and is a brain-gut peptide that acts as an anorexigenic signal in mammals (Blevins et al., 2008; Karra et al., 2009; Zhang et al., 2012). Interestingly, one of the first studies showing an effect of PYY on feeding in mammals used fish PYY (Balasubramaniam et al., 1992). PYY was first shown to be present in the gastrointestinal tract of fish by immunochemical methods in the 1980's (daddy sculpin Cottus scorpius and Baltic sea cod Gadus morhua callarias El-Salhy, 1984) and first cloned and detected in the brain by ISH in an Agnatha, the river lamprey (Lampetra fluviatilis; Söderberg et al., 1994). The first indirect evidence of a role for PYY in feeding in fish was provided in sea bass, in which PYY transcripts were detected in brain areas regulating feeding (Cerdá-Reverter et al., 2000) and the first direct evidence of an anorexigenic role for PYY in fish was provided by IP injections of goldfish PYY in goldfish (Gonzalez and Unniappan, 2010). Peripheral injections of species-specific PYY also decrease food intake in another cyprinid, the grass carp (Chen et al., 2013) and in Siberian sturgeon Acipenser baerii (Acipenseriformes) (Chen et al., 2015). However, in channel catfish (Siluriformes), human PYY injections do not affect food intake or plasma glucose levels or hypothalamic POMC expression (Schroeter et al., 2015), suggesting perhaps that species-specific PYYs are needed to elicit an effect on feeding.
Fasting induces decreases in brain PYY expression in both goldfish (Gonzalez and Unniappan, 2010) and Ya fish (Yuan et al., 2014) (Cypriniformes) and in PPY intestinal expression in red-bellied piranha (Characiforme,) (Volkoff, 2014a), suggesting a role in satiety. However, fasting does not affect brain PYY expression in either cavefish (Characiforme) (Wall and Volkoff, 2013) or red-bellied piranha (Volkoff, 2014a), either brain or gut PYY mRNA expression in Atlantic salmon (Salmoniforme) (Murashita et al., 2009b), and induces increases in PYY gut expression in both yellowtail (Perciformes) (Murashita et al., 2006, 2007) and Japanese grenadier anchovy Coilia nasus (Clupeiformes) (Yang et al., 2016).
PYY mRNA expression increases post-feeding in the brain of goldfish (Gonzalez and Unniappan, 2010) and Ya fish (Yuan et al., 2014), cave fish (Wall and Volkoff, 2013) and Siberian sturgeon (Chen et al., 2015), in the intestine of grass carp (Chen et al., 2014) and in whole larval Atlantic halibut (Pleuronectiformes) (Gomes et al., 2015). However, in Atlantic salmon, brain PYY expression shows no periprandial changes (Valen et al., 2011; Kousoulaki et al., 2013), perhaps suggesting that PYY does not play a major role as a short-term satiety factor in salmonids.
Overall, it appears that in most fish examined to date, PYY might acts as an anorectic/satiety peptide, although this does not seem to hold true for all fish species (e.g., salmon, yellowtail, or catfish).