Cottonseed Protein as an Alternative Feed Ingredient for Fish: Nutritional Metabolism and Physiological Implications

Against the backdrop of the continuous expansion of the global aquaculture industry and the growing demand for high-quality feed protein, the development of sustainable alternative protein sources to fishmeal is crucial. Cottonseed protein, particularly cottonseed protein concentrate, has emerged as a highly promising plant-based alternative raw material due to its high protein content and cost advantages. This review systematically evaluates the application effects, challenges, and mechanisms of action of cottonseed protein in fish feed. Core analysis indicates that the primary limiting factor of cottonseed protein is the antinutritional factor free gossypol. High-level replacement (typically >30%) of fishmeal can inhibit fish growth, reduce protein deposition, and impair intestinal health. These adverse effects are closely associated with the downregulation of the hepatic mTOR signaling pathway—a central regulator of protein synthesis and cell growth—shifting the organism’s energy allocation from growth to stress adaptation. Furthermore, the unique fatty acid profile of cottonseed protein may exacerbate energy metabolism imbalance. To overcome gossypol toxicity, physical, chemical, and biological detoxification technologies have been widely applied. Among these, biological methods (such as Bacillus subtilis fermentation and CotA laccase-catalyzed degradation) are particularly outstanding, not only efficiently removing gossypol (removal rate > 90%) but also degrading macromolecular proteins into more digestible and absorbable small peptides and amino acids, significantly enhancing the nutritional value of cottonseed protein. Although the application prospects for cottonseed protein are broad, gaps remain in current research, particularly concerning the deeper metabolic pathways, nutrient utilization efficiency, and long-term impacts on metabolic homeostasis of detoxified cottonseed protein in fish. Future research needs to employ molecular nutrition and multi-omics technologies to elucidate its metabolic mechanisms and optimize detoxification processes and precision feeding strategies. Glandless cottonseed varieties, which fundamentally address the gossypol issue, are considered the most transformative development direction. Through continuous technological innovation, cottonseed protein is expected to become a core feed protein ingredient promoting the sustainable development of the global aquaculture industry.