Rabbit meat extract alleviates diet-induced obesity via adipose browning with identification of a novel bioactive peptide

Metabolic disorders are primarily driven by the pathological buildup of adipose tissue resulting from a sustained caloric surplus. Although rabbit meat is considered a nutritionally valuable protein source, its potential role in metabolic regulation has not been fully characterized. The present research focused on investigating the anti-obesity properties of rabbit meat extract (RME) and determining its bioactive peptides. To this end, male mice received a high-fat diet (HF) for a 15-week period, with RME administered orally at 150 or 300 mg/kg dosages. We subsequently analyzed body weight fluctuations, fat tissue histology, and liver lipid deposition to monitor metabolic shifts. RME supplementation markedly reduced HF-induced body weight gain, adipocyte hypertrophy, and hepatic lipid deposition. These effects were associated with downregulation of adipogenic regulators (C/EBPα, PPARγ, and aP2) and upregulation of thermogenesis-related markers (UCP1, PGC1α, and PRDM16) in adipose tissue. To elucidate the molecular pathways involved, RME-derived peptides were identified via LC–MS/MS analysis, leading to the selection of five functional candidates. Of these, peptide-3(GEAGPQGARG) exhibited the most potent bioactivity, characterized by the upregulation of thermogenic genes and the concurrent downregulation of adipogenic markers within adipocytes. Notably, in adipocytes, the regulatory effects of GEAGPQGARG on AMPK–ACC signaling and thermogenesis-related markers were attenuated by Compound C, suggesting that AMPK-associated signaling may partly contribute to the metabolic activity of this peptide.