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

**Authors:** Emily Schifano, Paola Zinno, Fausta Natella, Laura Pompa, Erica Sonaglia, Sophia Spaziani, Mohammad Sharbaf, Francesco Esposito, Teresa Cirillo, Jonathan Squillante, Giuseppe Maglione, Patrizia Mancini, Antonio Angeloni, Maria Laura Santarelli, Chiara Devirgiliis, Daniela Uccelletti

PMC · DOI: 10.3390/molecules31050887 · 2026-03-06

## TL;DR

Coffee silverskin helps reduce obesity in worms by improving metabolism and reducing stress, suggesting it could be used in functional foods.

## Contribution

CSS is shown to alleviate high-glucose-diet-induced obesity via metabolic and antioxidant pathways in C. elegans.

## Key findings

- CSS reduced lipid accumulation and modulated metabolic genes like nhr-49 in worms on a high-glucose diet.
- CSS lowered ROS levels and upregulated antioxidant genes, indicating reduced oxidative stress.
- CSS modulated serotonergic signaling and promoted probiotic growth, suggesting prebiotic potential.

## Abstract

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.

## Linked entities

- **Genes:** GSTM2 (glutathione S-transferase mu 2) [NCBI Gene 2946], SOD3 (superoxide dismutase 3) [NCBI Gene 6649], nhr-49 (NR LBD domain-containing protein;Nuclear hormone receptor family member nhr-49) [NCBI Gene 172839], TPH1 (tryptophan hydroxylase 1) [NCBI Gene 7166], Ser6 (Serine protease 6) [NCBI Gene 33073], daf-2 (Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase) [NCBI Gene 175410], daf-16 (Forkhead box protein O) [NCBI Gene 172981]
- **Species:** Caenorhabditis elegans (taxon 6239)

## Full-text entities

- **Genes:** nhr-49 (NR LBD domain-containing protein;Nuclear hormone receptor family member nhr-49) [NCBI Gene 172839], sod-3 (Superoxide dismutase) [NCBI Gene 181748], daf-2 (Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase) [NCBI Gene 175410], daf-16 (Forkhead box protein O) [NCBI Gene 172981], ser-6 (G-protein coupled receptors family 1 profile domain-containing protein) [NCBI Gene 259560], tph-1 (Biopterin-dependent aromatic amino acid hydroxylase family profile domain-containing protein) [NCBI Gene 174227], gst-4 (Glutathione S-transferase 4) [NCBI Gene 177886]
- **Diseases:** Obesity (MESH:D009765)
- **Chemicals:** serotonin (MESH:D012701), ROS (MESH:D017382), Glucose (MESH:D005947), polyphenols (MESH:D059808), fatty acid (MESH:D005227), Silverskin (-), lipid (MESH:D008055), xanthines (MESH:D014970)
- **Species:** Caenorhabditis elegans (species) [taxon 6239]

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12986101/full.md

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Source: https://tomesphere.com/paper/PMC12986101