Coffee Silverskin Supplementation Alleviates High-Glucose-Diet-Induced Obesity by Modulating Lipogenic Gene Expression in Caenorhabditis elegans Model

Coffee silverskin (CSS), the major by-product of coffee roasting, is reported to contain bioac-tive compounds, including xanthines and polyphenols, showing promising potential for food and nutraceutical applications. This study investigated the beneficial effects of CSS hy-droalcoholic extracts, which were chemically characterized by Attenuated Total Reflectance–Fourier-Transform Infrared Spectroscopy and ElectroSpray Ionization tandem Mass Spec-trometry, on Caenorhabditis elegans physiology. CSS supplementation improved healthspan-related parameters and delayed aging-associated functional decline, without significantly ex-tending lifespan in wild-type nematodes. Treated worms exhibited a 57% reduction in reac-tive oxygen species (ROS) levels and upregulation of antioxidant genes (gst-4 and sod-3), suggesting that CSS mitigates oxidative stress through the DAF-2/DAF-16 pathway. Under high-glucose diet conditions, CSS reduced lipid droplet accumulation and modulated the expression of metabolic genes, including upregulation of nhr-49 which is a key regulator of fatty acid oxidation. CSS restored lipid homeostasis and rescued the shortened lifespan of obese nhr-49 mutant worms, suggesting enhanced β-oxidation. Moreover, CSS modulated serotonergic signaling by increasing tph-1 and ser-6 expression, linking its effects to seroto-nin-mediated regulation of fat metabolism. Finally, CSS promoted the growth of probiotic strains, suggesting potential prebiotic properties. Overall, these findings identify CSS as a metabolic modulator capable of alleviating oxidative and metabolic stress, supporting its sustainable application in the development of functional foods and nutraceuticals.