Natural triterpenoid compounds modulating AMPK-mediated energy metabolism in Caenorhabditis elegans model of obesity

Triterpenoids possess promising anti-obesogenic potential modulating multiple key molecular mechanisms, which is attributed to their structural diversity. By targeting essential signaling pathways such as the adenosine monophosphate protein kinase (AMPK) and sirtuin (SIRT) pathway, triterpenoids may represent an effective strategy for obesity management [ 1 ]. Moreover, these compounds are known to counteract systemic low-grade inflammation, which is a critical obesity-related metabolic dysfunction [ 2 ]. Within the current study we have evaluated the anti-obesogenic activity of selected triterpenoids (gypenoside XLIX, pulchinenoside C, momordin Ic) as they have been scarcely investigated in the context of obesity and metabolic diseases. Therefore, we monitored key body parameters (as mean width, length, and surface area), and evaluated the effect on the lipid accumulation in a Caenorhabditis elegans obesity model. The selected compounds were applied at a treatment concentration of 100 μM in both wild-type and MIR13 strains. Orlistat was utilized as a control treatment, being an approved anti-obesity medication. Our findings demonstrated that the selected triterpenoids effectively modulate lipid metabolism in nematodes supplemented with 2% glucose. Collectively, the data suggest a rationale for further investigation of gypenoside XLIX, pulchinenoside C, momordin Ic as modulators of glucose-induced lipid accumulation and identification of specific molecular mechanisms of action in the context of obesity and metabolic disorders. 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