Defective protein persulfidation is involved in obesity associated skeletal muscle dysfunction: role of SIRT-1

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 (H2S) signaling contributes to obesity-related SKM dysfunction. Muscle tissues fro...

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Main Authors: M. Smimmo, V. Casale, D. D'Andrea, I. Bello, N. Iaccarino, F. Romano, V. Brancaleone, E. Panza, R. d’Emmanuele di Villa Bianca, A. Katsouda, E. Mitidieri, I. Antoniadou, A. Papapetropoulos, F. Maione, S. Castaldo, M. Friuli, A. Romano, S. Gaetani, R. Sorrentino, A. Randazzo, G. Cirino, M. Bucci, M. Filipovic, V. Vellecco
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Redox Biology
Subjects:
H2S donors
Skeletal muscle
Persulfidation
Sodium palmitate
Db/db mice
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231725001582
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Summary: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 (H2S) 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−/− mice show similar deficits as db/db mice, confirming the role of MPST. H2S 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 H2S 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 H2S in obesity-associated SKM dysfunction via SIRT-1 persulfidation, highlighting the importance of the MPST/H2S pathway in maintaining healthy SKM function.
ISSN:2213-2317

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