Abstract <p>The mandarin fish (<i>Siniperca chuatsi</i>) is a typical carnivorous teleost. To evaluate the physiological impact of formulated diet feeding on hepatic lipid metabolism, this study compared fish fed formulated diet with a control group provided with live prey. We analyzed liver histology, serum and tissue biochemical profiles, and the expression of key genes involved in lipid homeostasis and inflammatory signaling. The results showed that the formulated diet–fed group displayed significant histological changes, including vacuolization, nuclear pyknosis, and infiltration of inflammatory cells. Additionally, intracellular neutral lipid droplets exhibited localized aggregation and significant enlargement, correlated with increased hepatic triglyceride levels. The hepatic fatty acid profile underwent substantial modification, marked by a reduction in saturated and monounsaturated fatty acids and an increase in polyunsaturated fatty acids. Diet-fed fish had higher <i>ω</i>-6 fatty acids and <i>ω</i>-6/<i>ω</i>-3 ratio in comparison to the control group. In terms of lipid metabolism, transcriptional analysis showed that <i>Atgl</i> and <i>Fasn</i> were significantly downregulated, whereas <i>Acaca</i> was significantly upregulated. Moreover, protein expression of lipogenic enzymes (fatty acid synthase and acetyl-CoA carboxylase) was increased, but proteins that help fatty acid oxidation and transport (carnitine palmitoyltransferase-I and lipoprotein lipase) were decreased. Although oxidative stress markers (catalase, superoxide dismutase, and malondialdehyde) remained almost constant, glutathione peroxidase activity and the activities of aspartate aminotransferase and alanine aminotransferase were markedly increased, referring to impaired liver function. Regarding immunological responses, feeding formulated diet upregulated the transcription levels of the pro-inflammatory cytokines (<i>tnf</i> and <i>il6</i>) and the anti-inflammatory cytokine <i>il10</i>. Overall, these results indicate that formulated diet cause hepatic lipid dysregulation and irregular deposition in mandarin fish, leading to liver damage and eliciting systemic immune responses.</p> Highlights <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Formulated diet induces abnormal hepatic lipid droplet accumulation and alter fatty acid composition.</p> </ItemContent> <ItemContent> <p>Diet feeding increases hepatic lipid synthesis and reduces lipid breakdown.</p> </ItemContent> <ItemContent> <p>Diet feeding damages liver tissue and elevates aspartate aminotransferase, alanine aminotransferase, and inflammatory responses.</p> </ItemContent> </UnorderedList></p>