Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement

Understanding and regulating fish growth is vital for the economic sustainability of aquaculture. The melanocortin-3 and -4 receptors (MC3R/MC4R, known as neural MCRs), integral components of the leptin-melanocortin circuit, play crucial roles in vertebrate energy homeostasis and growth. Abnormal neural MCR signaling contributes to human obesity. In teleosts, Mc4r was first comprehensively studied in goldfish in 2003. Since then, Mc4r has been characterized in various teleosts. Genetic and pharmacological reduction of neural Mcr signaling can increase feeding or growth in several fish models, although its aquaculture value must be evaluated using production endpoints such as feed conversion, body composition, reproduction, welfare, and biosafety. Furthermore, neural Mcrs also play a role in modulating reproductive processes and sexual function in teleosts. This review systematically examines recent progress on the roles of fish neural Mcrs, offering an overview of basic molecular characteristics, tissue distribution, and pharmacology. Physiological roles and mechanisms in growth regulation are reviewed. Finally, the potential and limitations of targeting neural Mcrs for aquaculture-relevant traits are discussed. This work contributes to our understanding of the evolution of energy homeostasis regulation in vertebrates, providing a foundation for healthier and more efficient aquaculture practices.