Behind melanocortin antagonist overexpression in the zebrafish brain: Behavioural and transcriptomic approaches

Abstract

Melanocortins are small peptides encoded by a complex precursor called proopiomelanocorin (POMC). They are mainly composed of an adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormones (α-, β- γ- and δ-MSH). These peptides exert its physiological actions by binding to 5 G protein-coupled receptors (MC1R-MC5R). Atypically, melanocortin signaling is regulated also by endogenous antagonists, agoutisignalling protein (ASIP) and agouti-related protein (AGRP) that compete with melanocortin peptides by binding to MCRs. ASIP is expressed mainly in the ventral skin where it inhibits melanogenesis by binding to MC1R. AGRP binds MC3R and MC4R in the brain for the regulation of energy balance and growth. Overexpression of ASIP1 in zebrafish results in dorsal inhibition of melanogenesis. However, zebrafish overexpressing ASIP growth faster and exhibit increased food intake level but similar response to stressful conditions. In order to improve our understanding of the molecular mechanisms and markers associated with the central melanocortin inhibition we characterized the brain transcriptome induced by ASIP overexpression through microarray analyses, resulting in the identification of multiple ASIPinduced mRNAs. Interestingly some genes regulating behavioral processes in zebrafish were modulated by melanocortin signaling blocking