Nomilin counteracts glucose-induced mitochondrial dysfunction in Caenorhabditis elegans model of obesity

Mitochondrial dysfunction plays a crucial role in the development of cardiovascular diseases, metabolic syndrome, obesity, diabetes, and neurodegenerative disorders. Natural triterpenoid compounds have been reported with diverse pharmacological properties, including anti-inflammatory, anti-obesogenic, and anti-aging effects [ 1 ]. Nomilin, a bitter-taste limoloid that is enriched in citrus peels, has been identified as a human pregnane X receptor (hPXR) agonist that extends lifespan and improves healthspan [ 2 ]. The data obtained in our preliminary studies has confirmed that nomillin reduces lipid accumulation in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner. Here, we aim to gain a more profound characterization of the effect of nomillin (100 μM) on mitochondrial bioenergetics by utilizing a glucose-induced obesity model in Caenorhabditis elegans [ 3 ]. We assessed the changes in the lipid storage in C. elegans transgenic strains fed on elevated glucose through GFP-based confocal fluorescent detection. Furthermore, we evaluated the changes in mitochondrial dynamics through the MitoView Green and TMRE co-staining to enhance our understanding of the nomilin mode of action. Our results revealed that nomilin enhanced mitochondrial dynamics, lipid beta-oxidation in the mitochondria and genes related to AMPK/SIRT signalling pathway in glucose-induced obesity model in C. elegans . Taken together, we have provided insights on the molecular mechanism that drives the anti-obesogenic effect of nomilin and its role on mitochondrial bioenergetics regulation. Funding This research received funding from the Bulgarian National Science Fund (Contract number KП-06-Н83/4) and by the European Regional Development Fund through Programme Research Innovation and Digitalisation for Smart Transformation, Grant agreement № BG16RFPR002-1.014-0003-C01. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany