Triterpenoid‐Enriched Bitter Melon Leaf Extract Mitigates Hepatic Lipotoxicity and Necroptosis in Diet‐Induced Obese Zebrafish

Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to obesity, lipid dysregulation, and hepatic oxidative stress. Wild bitter melon (WBM, Momordica charantia L. var. abbreviata Ser.) leaves contain triterpenoids that have demonstrated anti‐inflammatory and hepatoprotective activities. Methods A diet‐induced obesity (DIO) zebrafish model was established using a hyperphagic feeding regimen. The effects of a triterpenoid‐enriched extract (TEE) derived from WBM leaves were evaluated. Metabolic parameters, hepatic lipid accumulation, oxidative stress markers, and gene expression profiles were analyzed. Results TEE treatment significantly reduced fasting blood glucose and cholesterol levels without affecting body weight or body mass index. Hepatic lipid accumulation and triglyceride levels were markedly decreased, accompanied by downregulation of genes associated with lipogenesis and cholesterol metabolism. TEE also reduced hepatic lipid peroxidation, as indicated by decreased thiobarbituric acid–reactive substances (TBARS), while reduced glutathione levels remained unchanged. In addition, expression of necroptosis‐related genes was suppressed. Conclusions TEE exerts hepatoprotective effects in a zebrafish DIO model by improving lipid and glucose metabolism and attenuating lipid‐associated oxidative damage. These findings highlight the potential of TEEs as natural interventions for MASLD and support the use of zebrafish as a model for studying metabolic improvements independent of weight reduction.