Unlabelled: Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes , , , , , , and . Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the and single mutants and ; double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04017-3.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143156PMC
http://dx.doi.org/10.1007/s13205-024-04017-3DOI Listing

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