Defective protein persulfidation is involved in obesity associated skeletal muscle dysfunction: role of SIRT-1
Ectopic fat deposition in skeletal muscle (SKM) due to obesity leads to biochemical and morphological alterations that deteriorate SKM quality and performance. Here, we show that impaired MPST-derived hydrogen sulfide (H<sub>2</sub>S) signaling contributes to obesity-related SKM dysfunction. Muscle tissues from obese db/db mice exhibit reduced MPST expression, correlating with decreased protein persulfidation and muscle performance in vivo. Mpst<sup>-/-</sup> mice show similar deficits as db/db mice, confirming the role of MPST. H<sub>2</sub>S supplementation improves locomotor activity in db/db mice and restores protein persulfidation, including SIRT-1. Myotubes placed in an "obese environment" display a downregulation of MPST, coupled with a reduced SIRT-1 persulfidation leading to an inflammatory state. Exogenous H<sub>2</sub>S exerts beneficial effects recovering SIRT-1 persulfidation/activity. Finally, muscle biopsies from obese individuals show reduced MPST expression, underscoring the translational relevance to human SKM health. Our study unveils a crucial role for MPST-derived H<sub>2</sub>S in obesity-associated SKM dysfunction via SIRT-1 persulfidation, highlighting the importance of the MPST/H<sub>2</sub>S pathway in maintaining healthy SKM function.
Authors
- I Bello
- Giuseppe Cirino (ORCID: https://orcid.org/0000-0003-3954-4083)
- Miloš R. Filipović (ORCID: https://orcid.org/0000-0003-0060-0041)
- Emma Mitidieri (ORCID: https://orcid.org/0000-0003-4372-9611)
- Nunzia Iaccarino (ORCID: https://orcid.org/0000-0001-7544-5512)
- Adele Romano (ORCID: https://orcid.org/0000-0003-3874-2627)
- Martina Smimmo (ORCID: https://orcid.org/0000-0001-9643-7378)
- Vincenzo Brancaleone (ORCID: https://orcid.org/0000-0002-0063-659X)
- D D'Andrea
- Federica Maione (ORCID: https://orcid.org/0000-0003-2789-799X)
- A. Katsouda
- Francesca Romano (ORCID: https://orcid.org/0000-0001-9803-0635)
- Marzia Friuli (ORCID: https://orcid.org/0000-0001-7481-3424)
- Valentina Vellecco (ORCID: https://orcid.org/0000-0002-5674-9112)
- Mariarosaria Bucci (ORCID: https://orcid.org/0000-0001-5502-4315)
- Antonio Randazzo (ORCID: https://orcid.org/0000-0002-9192-7586)
- Raffaella Sorrentino (ORCID: https://orcid.org/0000-0002-0284-5424)
- Andreas Papapetropoulos (ORCID: https://orcid.org/0000-0002-4253-5930)
- Roberta d’Emmanuele di Villa Bianca (ORCID: https://orcid.org/0000-0003-0992-6400)
- Ivi Antoniadou (ORCID: https://orcid.org/0000-0002-0307-9880)
- Elisabetta Panza (ORCID: https://orcid.org/0000-0003-0274-4671)
- V. Casale
- Silvana Gaetani
- Sigismondo Castaldo (ORCID: https://orcid.org/0000-0002-2886-6856)
Institutions
- Academy of Athens (GR)
- Ospedale Antonio Cardarelli (IT)
- University of Naples Federico II (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Redox Biology
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1016/j.redox.2025.103645
- Citations
- 3
- Primary Topic
- Biochemical effects in animals
- Type
- article
- Field-Weighted Citation Impact
- 3.49
Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Ministero dell'Università e della Ricerca
- Horizon 2020 Framework Programme
- European Research Council
- HORIZON EUROPE European Research Council