# Spexin-Mediated Dietary Adaptation in Siniperca chuatsi: Molecular Characterisation and Functional Insights into FABP2 Interaction

## TL;DR

This study explores how the spexin gene in mandarin fish regulates appetite and metabolism, especially during fasting and feeding, and identifies a new interaction with a protein involved in lipid metabolism.

## Contribution

The study identifies fatty acid-binding protein 2 as a novel interaction partner of spexin in fish, revealing a new regulatory mechanism in lipid metabolism.

## Key findings

- Spexin expression in liver is significantly higher than in muscle in mandarin fish.
- Spexin expression in muscle, liver, and intestine increases then decreases during fasting, while the opposite occurs in brain and stomach.
- Fatty acid-binding protein 2 interacts with spexin, suggesting a role in lipid metabolism via the PPAR signaling pathway.

## Abstract

Growth performance represents a key metric in piscine genetic breeding. The growth-related gene spexin (spx) critically regulates appetite and metabolic homeostasis. This study characterized the open reading frame (ORF) of spx in mandarin fish (Siniperca chuatsi), an economically significant teleost, revealing its peak expression in the liver. We further elucidated the regulatory profile of spx during starvation and feeding adaptation. During a 7-day fasting regimen, spx expression in muscle, liver, and intestine exhibited an initial increase followed by a decline, whereas an inverse expression trajectory was noted in the brain and stomach. Larger individuals displayed significantly diminished spx expression in the liver and brain relative to their smaller counterparts, yet elevated expression was detected in the stomach. Using glutathione S-transferase (GST) pull-down assays, fatty acid-binding protein 2 was identified as a novel interaction partner of SPX, suggesting a potential mechanism whereby SPX modulates lipid metabolism via the peroxisome proliferator-activated receptor (PPAR) signaling pathway to mediate feeding adaptation. This study provides novel mechanistic insights into the role of SPX in nutritional adaptation in S. chuatsi, and establishes a foundational framework for subsequent genetic breeding initiatives.

Neuropeptide Q (spexin, spx) is a pleiotropic signalling molecule that regulates appetite and metabolism primarily via activation of galanin and melanocortin receptors. Here, we cloned the open reading frame (ORF) of spx from Siniperca chuatsi (Scspx), characterised its spatiotemporal expression, elucidated spx regulatory features during starvation and feed adaptation, and identified SPX-interacting proteins using glutathione S-transferase pull-down and mass spectrometry. The Scspx ORF was 312 bp, encoding 103 amino acids. The predominant expression of spx was found in the liver of feed-trained S. chuatsi, where it was 17.36-fold greater than in muscle. During fasting (0, 3, 5, and 7 d), spx expression in the muscle, liver, and intestine initially increased and then declined, whereas brain and stomach tissues exhibited the opposite tendency. Compared to the smallest individuals, hepatic and brain spx expression was substantially lower in the largest individuals, whereas stomach expression was higher (p < 0.05). Fatty acid binding protein 2 was identified as a novel SPX-interacting partner, implicating SPX in feed adaptation through lipid metabolic regulation via the peroxisome proliferator-activated receptor signalling pathway. Our results provide the first evidence of a direct SPX-FABP2 interaction in fish, pointing to a coordinated role in downstream gene regulation. This work hereby uncovers a novel regulatory axis within the piscine energy metabolism network. These findings provide new insight into the regulatory role of SPX in feed adaptation in S. chuatsi, offering a foundation for genetic analysis.