Pro-opiomelanocortin (POMC) family of peptides
Proopiomelanocortin (POMC) is a common precursor that is processed post-translationally to generate melanocortin peptides [α-, β-, and γ-melanocyte-stimulating hormone (α-, β-, γ-MSH)], adrenocorticotropic hormone (ACTH) and other hormones that include β-endorphin (β-END) and β-lipotropic hormone (β-LPH) (Adan et al., 2006; Takahashi, 2016). POMC is mainly produced in the vertebrate pituitary, but is also found in brain, in particular the arcuate nucleus (ARC) of the hypothalamus. Receptors for melanocortin peptides include five subtypes (MC1R- MC5R) (Takahashi, 2016). In mammals, POMC and α-MSH have been shown to be involved in the regulation of appetite and energy homeostasis: POMC neurons suppress appetite by releasing α-MSH, which is an agonist at the anorectic melanocortin-4 receptor (MC4R) (Adan et al., 2006; Cone, 2006; Sohn, 2015).
Teleost fish lack γ-MSH and the POMC gene encodes an extra MSH (δ-MSH) in elasmobranchs (Cérda-Reverter et al., 2011). Fish POMC was first identified in Salmoniformes (Kawauchi, 1983; Kitahara et al., 1988) and Cypriniformes (Arends et al., 1998), followed by the identification of several forms in other fish species. As in other vertebrates, fish POMC is mainly expressed in the pituitary gland, but also within the lateral tuberal nucleus, which is equivalent to the mammalian ARC (Cérda-Reverter et al., 2011). POMC, α-MSH and the MC4R have been shown to regulate feeding in a few fish species.
In goldfish, fasting does not seem to affect hypothalamic POMC mRNA expression levels (Cerdá-Reverter et al., 2003), but ICV administration of [Nle4, d-Phe7]- α-MSH, a melanocortin agonist, inhibits food intake (Cerdá-Reverter et al., 2003), suggesting the melanocortin system participates in central regulation of food intake in Cypriniformes (Cerdá-Reverter et al., 2003). In addition, ICV injections of a MSH (MC4R) receptor agonist (melanotan II) suppress hypothalamic NPY expression (Kojima et al., 2010), and hypothalamic α-MSH-containing neurons are in close contact to NPY-containing nerve fibers, suggesting that the anorexigenic actions of the melanocortin system are mediated in part by an inhibition of the NPY system. In zebrafish larvae, although early ISH studies could not detect fasting-induced changes in hypothalamic POMC transcript levels (Song et al., 2003), more recent qPCR studies indicate that POMCa expression decreases in starved fish (Shanshan et al., 2016). In addition, GH-transgenic zebrafish, who have increased feeding, display down-regulation of POMC (Dalmolin et al., 2015), consistent with an anorexigenic role for POMC-derived peptides in Cypriniformes.
Similarly, in salmonids, POMC/α-MSH appears to have an anorexigenic role. In coho salmon, IP injections of α-MSH decrease food intake (White et al., 2016), in rainbow trout, fasting induces a decrease in hypothalamic expression of POMC-A1 (but not POMC-A2 or POMC-B) (Leder and Silverstein, 2006), and in Atlantic salmon, expression of both POMC-A1 and POMC-B increase after feeding (Valen et al., 2011). Interestingly, α-MSH treatment does not affect feeding of GH-transgenic coho salmon (White et al., 2016), despite similar hypothalamic POMC and MC4R mRNA expression levels compared to non-transgenic fish (Kim et al., 2015), suggesting that the actions of α-MSH might be inhibited by high expression levels of GH and/or AgRP.
In both olive (Kang and Kim, 2015) and Barfin flounder (Takahashi et al., 2005) (Pleuronectiformes), pituitary POMC-C (isoforms 1, 2, and 3) mRNAs are not affected by fasting, suggesting pituitary POMC might not directly related to appetite regulation. However, in fasted halibut larvae, whole brain POMC-C mRNA expression is higher in unfed fish 30 min after re-feeding compared to continuously fed fish (Gomes et al., 2015), suggesting a short-term regulation of appetite. Given the small number of studies available, and the variation in experimental protocols (adults vs. larvae, pituitary vs. brain, long-term vs. short-term feeding), conclusions are difficult to drawn regarding the role of POMC in flatfish.