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Kisspeptin Mitigates Hepatic De Novo Lipogenesis in Metabolic Dysfunction Associated Steatotic Liver Disease

ABSTRACT: Emerging evidence suggests that the peptide hormone kisspeptin, signaling via the kisspeptin 1 receptor (KISS1R), decreases hepatic steatosis and protects against metabolic dysfunction-associated steatotic liver disease (MASLD). De novo lipogenesis (DNL) is a key contributor to the pathogenesis of MASLD. This study aimed to determine whether kisspeptin treatment of obese, diabetic mice directly attenuates DNL. DNL was assessed in kisspeptin-treated (KPA) or phosphate-buffer saline (PBS)-treated mouse livers, using a mouse model of MASLD employing metabolic tracing using 2H2O-enriched water and mass spectrometry. Kisspeptin-treated steatotic livers demonstrated a decrease in DNL of free fatty acids (FFA), known to be associated with type 2 diabetes, steatosis, and hepatocellular carcinoma. Enhancement of KISS1R signaling has a therapeutic effect in limiting DNL, suggesting a crucial role in restricting the pathogenesis and progression of MASLD.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Moshmi Bhattacharya

PROVIDER: MSV000098033 | MassIVE | Thu May 29 13:26:00 BST 2025

REPOSITORIES: MassIVE

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