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ARS Home » Northeast Area » Leetown, West Virginia » Cool and Cold Water Aquaculture Research » Research » Publications at this Location » Publication #429692
Research Project: Improving the Efficiency of Salmonid Aquaculture

Location: Cool and Cold Water Aquaculture Research

Title: Central activation of chaperone-mediated autophagy reduces appetite by fine-tuning hypothalamic amino acid pools: new insights from fish

Author
item REJI, STEFFI - Inrae
item VELEZ, EMILIO - Inrae
item BLANCO, AYELEN - University Of Vigo
item HERAUD, CECILE - Inrae
item DIAS, KARINE - Inrae
item STELLA, ALEXANDRE - University Of Toulouse
item BURLET-SCHILTZ, ODILE - University Of Toulouse
item SCHNEBERT, SIMON - Inrae
item ROY, JEROME - Inrae
item BEAUMATIN, FLORIAN - Inrae
item Cleveland, Beth
item SOENGAS, JOSE - University Of Vigo
item SEILIEZ, IBAN - Inrae

Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2026
Publication Date: 1/12/2026
Citation: Reji, S., Velez, E., Blanco, A., Heraud, C., Dias, K., Stella, A., Burlet-Schiltz, O., Schnebert, S., Roy, J., Beaumatin, F., Cleveland, B.M., Soengas, J., Seiliez, I. 2026. Central activation of chaperone-mediated autophagy reduces appetite by fine-tuning hypothalamic amino acid pools: new insights from fish. American Journal of Physiology - Cell Physiology. 330(3):590-604. https://doi.org/10.1152/ajpcell.00765.2025.
DOI: https://doi.org/10.1152/ajpcell.00765.2025

Interpretive Summary: Food intake, which is largely regulated by appetite, is a primary driver of growth performance in fish. However, the processes regulating appetite are not well understood, particularly within brain. In this study the role of chaperone mediated autophagy (CMA) was investigated as a mechanism regulating appetite in the brain of rainbow trout. Findings indicate that CMA activity in the brain inversely correlates with feed intake and regulates local amino acid availability. These findings reveal a previously unrecognized role for CMA in the central regulation of nutrient sensing and feeding behavior in fish, indicating that novel production strategies targeting the CMA mechanism could be beneficial for improving appetite and growth performance.

Technical Abstract: 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 for the first time 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 first 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 indicated that CMA may influence FI, at least in part, by modulating hypothalamic free amino acid availability through ribosomal protein degradation. Through this mechanism, CMA may contribute to the precise regulation of satiety and represent a promising target for therapeutic strategies aimed at treating metabolic disorders and obesity, as well as for nutritional interventions to improve feed efficiency and promote more sustainable growth practices in aquaculture.