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 bioactive compounds, including xanthines and polyphenols, showing promising potential for food and nutraceutical applications. This study investigated the beneficial effects of CSS hydroalcoholic extracts, which were chemically characterized by Attenuated Total Reflectance–Fourier-Transform Infrared Spectroscopy and ElectroSpray Ionization tandem Mass Spectrometry, on Caenorhabditis elegans physiology. CSS supplementation improved healthspan-related parameters and delayed aging-associated functional decline, without significantly extending lifespan in wild-type nematodes. Treated worms exhibited a 57% reduction in reactive 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 serotonin-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.