Chaperone-Mediated Autophagy (CMA) is a key lysosomal proteolytic pathway essential for cellular homeostasis and metabolism, with dysfunction linked to various human diseases. While extensively studied in humans and mice, CMA was only recently identified in fish, paving the way for novel and evolutionary research perspectives. Here, we demonstrate a role for CMA in regulating feed intake (FI) in rainbow trout ( Oncorhynchus mykiss), a major aquaculture species and a widely used model in numerous research fields, including physiology, evolutionary genetics, toxicology, immunology, and nutrition. Specifically, we observed that feed deprivation induces an increase in the CMA activation score – a reliable proxy for CMA activity – in the hypothalamus, a central brain region involved in the regulation of feeding behavior. To probe its functional relevance, we intracerebroventricularly (ICV) injected the CMA activator CA77.1 and found a significant reduction in FI levels, suggesting a regulatory role for CMA in appetite. Further analysis suggested that CMA may regulate FI partly through changes in hypothalamic free amino acid availability, with ribosomal protein degradation potentially contributing to this mechanism. Through this mechanism, CMA may play a critical role in the precise regulation of satiety and represent a promising target for therapeutic strategies aimed at treating metabolic disorders, as well as for nutritional interventions to improve feed efficiency and promote more sustainable growth practices in aquaculture.
Reji et al. (Mon,) studied this question.