| Summary: | This study estimated the effect of substituting fishmeal completely with cottonseed protein concentrate (CPC) in the diet of sturgeon (<i>Acipenser schrenckii</i>) on growth, digestive physiology, and hepatic gene expression. A control diet containing fishmeal and an experimental diet based on CPC was designed. The study was conducted for 56 days in indoor recirculating aquaculture systems. The results showed that weight gain, feed efficiency, and whole-body essential amino acids (EAAs) all decreased significantly in the experimental group, while whole-body non-essential amino acids (NEAAs) and serum transaminase activity increased (<i>p</i> < 0.05). The activity of digestive enzymes in the mid-intestine was significantly reduced (<i>p</i> < 0.05), and liver histology revealed fatty infiltration of hepatocytes. The hepatic transcriptome revealed an upregulation of genes linked to metabolism, including steroid biosynthesis, pyruvate metabolism, fatty acid metabolism, and amino acid biosynthesis. These findings indicate that fully replacing fishmeal with CPC harms <i>A. schrenckii</i> growth and physiology. This study provides valuable data for the development of improved aquafeeds and the use of molecular methods to evaluate the diet performance of sturgeon.
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