Nutritional intervention with glycyrrhetinic acid (GA) enhances growth and metabolic balance in channel catfish (Ictalurus punctatus) fed a high-fat diet.

This study investigated the protective effects of glycyrrhetinic acid (GA) supplementation on metabolic disturbances induced by a high-fat diet (HFD) in juvenile channel catfish (Ictalurus punctatus). Fish were fed a control diet, an HFD, or an HFD supplemented with 0.4, 0.8, and 1.2 mg/kg GA, respectively, for 8 weeks. Hepatic function, mitochondrial integrity, and metabolic gene expression were assessed. HFD significantly impaired protein efficiency ratio (PER) and relative feed intake (RFI) while promoting excessive lipid deposition and energy storage. These changes were accompanied by elevated plasma levels of liver enzymes (GOT, GPT), non-esterified fatty acids (NEFA), and pro-inflammatory cytokines (TNF-α, IL-6, MCP-1). Mitochondrial dysfunction was evident from reduced activities of succinate dehydrogenase, Na⁺, K⁺-ATPase, and complexes I and II, alongside increased cytosolic cytochrome c, indicating mitochondrial injury and apoptosis. HFD also suppressed expressions of mitochondrial genes (nd1, cytb) and disrupted glucose and lipid metabolism by altering key gene expression patterns. GA supplementation significantly reversed these pathological changes. It improved mitochondrial function, restored respiratory complex activities (particularly complex III), normalized gene expression related to mitochondrial biogenesis, glucose utilization (e.g., ampkα2, glut2), and lipid oxidation (e.g., cpt1, pparα), and reduced inflammation and hepatic damage. Overall, GA redirected energy utilization from lipid storage toward growth, suggesting its potential as a functional feed additive to mitigate high-fat diet-induced metabolic dysfunction in aquaculture species.