Agouti-related protein (or peptide, AgRP)
AgRP is a peptide released by hypothalamic NPY/AgRP neurons and is an endogenous antagonist of the melanocortin receptors MC3R and MC4R. AgRP plays a crucial role in the regulation of energy balance, as it increases food intake, by antagonizing the effects of the anorexigenic POMC product, α-melanocyte-stimulating hormone (α-MSH) (Sohn, 2015; Takeuchi, 2016).
In fish, AgRP has been identified in several species, including teleosts (e.g., goldfish Carassius auratus Cerdá-Reverter and Peter, 2003 and zebrafish Danio rerio Song et al., 2003, Atlantic salmon Salmo salar Murashita et al., 2009a, and seabass Dicentrarchus labrax Agulleiro et al., 2014, pufferfish Takifugu rubripes Klovins et al., 2004; Kurokawa et al., 2006), who have two genes products (AgRP1 and AgRP2; Cérda-Reverter et al., 2011) and Holocephali (Chimaeriforme, elephant fish Callorhinchus milii Västermark and Schioth, 2011).
AgRP appears to act as an orexigenic factor in Cypriniformes, as fasting increases hypothalamic AgRP expression in goldfish (Cerdá-Reverter and Peter, 2003), zebrafish (Song et al., 2003), and Ya fish Schizothorax prenanti (Wei et al., 2013). In addition, transgenic zebrafish overexpressing AgRP exhibit obesity, increased growth and adipocyte hypertrophy (Song and Cone, 2007). GH-transgenic common carp Cyprinus carpio, which display increased food intake, have higher hypothalamic AgRP1 mRNA expression levels than non-transgenic fish, further suggesting an orexigenic action (Zhong et al., 2013). However, this is contradicted by another study in carp showing that brain AgRP mRNA expression decreases after fasting and increases after re-feeding (Wan et al., 2012). In seabass (Perciforme), long-term fasting increases hypothalamic expression of AgRP1 but decreases that of AgRP2 (Agulleiro et al., 2014), suggesting an isoform-specific orexigenic action.
Within Salmoniformes, there is conflicting data with regards to the actions of AgRP. In Arctic charr Salvelinus alpinus, non-feeding fish have higher brain AgRP expression levels than feeding fish (Striberny et al., 2015) and transgenic coho salmon Oncorhynchus kisutch, which display increased feeding, have higher brain AgRP1 levels of mRNA than wild-type fish (Kim et al., 2015), suggesting an orexigenic role for AgRP. However, in Atlantic salmon, AgRP-1 brain mRNA levels decrease after fasting (Murashita et al., 2009a) and increase after feeding (Valen et al., 2011), rather pointing to an anorexigenic role.