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The melanocortin system is a key neuroendocrine network involved in the control of food intake and energy homeostasis in vertebrates. Within the hypothalamus, the system comprises two main distinct neuronal cell populations that express the neuropeptides proopiomelanocortin (POMC; anorexigenic) or agouti-related protein (AGRP; orexigenic). Both bind to the melanocortin-4 receptor (MC4R) in higher order neurons that control both food intake and energy expenditure. This system is relatively well-conserved among vertebrates. However, in Atlantic salmon ( Salmo salar  L.), the salmonid-specific fourth round whole-genome duplication led to the presence of several paralog genes which might result in divergent functions of the duplicated genes. In the current study, we report the first comprehensive comparative identification and characterization of Mc4r and extend the knowledge of Pomc and Agrp in appetite control in Atlantic salmon.  In silico  analysis revealed multiple paralogs for  mc4r  ( a1 ,  a2 ,  b1 , and  b2 ) in the Atlantic salmon genome and confirmed the paralogs previously described for  pomc  ( a1 ,  a2 , and  b ) and  agrp  ( 1  and  2 ). All Mc4r paralogs are relatively well-conserved with the human homolog, sharing at least 63% amino acid sequence identity. We analyzed the mRNA expression of  mc4r ,  pomc , and  agrp  genes in eight brain regions of Atlantic salmon post-smolt under two feeding states: normally fed and fasted for 4 days. The  mc4ra2  and  b1  mRNAs were predominantly and equally abundant in the hypothalamus and telencephalon, the  mc4rb2  in the hypothalamus, and  a1  in the telencephalon. All  pomc  genes were highly expressed in the pituitary, followed by the hypothalamus and saccus vasculosus. The  agrp  genes showed a completely different expression pattern from each other, with prevalent expression of the  agrp1  in the hypothalamus and  agrp2  in the telencephalon. Fasting did not induce any significant changes in the mRNA level of  mc4r ,  agrp , or  pomc  paralogs in the hypothalamus or in other highly expressed regions between fed and fasted states. The identification and wide distribution of multiple paralogs of  mc4r ,  pomc , and  agrp  in Atlantic salmon brain provide new insights and give rise to new questions of the melanocortin system in the appetite regulation in Atlantic salmon.

The Melanocortin System in Atlantic Salmon (Salmo salar L.) and Its Role in Appetite Control