Melanin concentrating hormone-sleep pressure loop regulates melanin degradation through both autophagic degradation and lysosomal hydrolysis in zebrafish.

Melanin-concentrating hormone (MCH) is a cyclic peptide initially isolated from salmon and later found to be conserved in mammals. It plays a role in regulating melanin changes and rhythmic behaviors such as sleep and feeding, though its relationship with these processes is not fully understood. Our preliminary research revealed significant differences in melanin degradation in zebrafish under varying light conditions, suggesting a link to MCH. This study aims to explore MCH's role in lighting-induced changes in rhythmic behavior patterns and melanin of zebrafish. Using the zebrafish model, we evaluated MCH expression under different lighting conditions and analyzed the effects of arousal-promoting and sleep-inducing agents. We also investigated the impact of exogenous MCH and its inhibitors on melanin degradation, behavioral changes, and differences in MCH expression to uncover potential regulatory relationships between MCH, sleep pressure, and melanin. In-depth research using flow cytometry, acridine orange staining, LysoTracker Red staining, and quantitative real-time PCR analysis of autophagy- and apoptosis-related genes showed that melanin degradation regulation depends on MCH expression levels. Sleep pressure can intervene in MCH's effects, forming a regulatory loop to jointly regulate melanin degradation. The influence of the MCH-sleep pressure loop on melanin degradation is closely tied to autophagic and lysosomal pathways. Our findings reveal a mutually regulatory loop in zebrafish between MCH and sleep pressure, affecting melanin degradation through these pathways.