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  • Resveratrol ameliorates muscle atrophy in chronic kidney disease via the axis of SIRT1/FoxO1.

Resveratrol ameliorates muscle atrophy in chronic kidney disease via the axis of SIRT1/FoxO1.

Phytotherapy research : PTR (2022-05-25)
Ruiting Wang, Weidong Yuan, Lu Li, Fei Lu, Lingling Zhang, Haifeng Gong, Xinzhong Huang
ABSTRACT

Chronic kidney disease (CKD) is often associated with muscle atrophy. However, the underlying molecular mechanisms are still not well understood. Here, we treated 5/6-nephrectomized (5/6Nx) rats with resveratrol and found that this treatment greatly improves renal function as evidenced by reduced proteinuria and cystatin C. Moreover, resveratrol ameliorates renal fibrosis by reducing transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF). Meanwhile, muscle atrophy in these 5/6Nx rats was largely attenuated by resveratrol. Immunoprecipitation revealed that SIRT1 physically interacts with FoxO1 in muscle, and this interaction was weakened in 5/6Nx rats. As a consequence, acetylated FoxO1 was increased in muscle of 5/6Nx rats. The application of resveratrol markedly reverses this trend. These data point out that SIRT1 is a key factor for linking renal disease and muscle atrophy. Indeed, both renal dysfunction and muscle atrophy were further aggravated by 5/6Nx in Sirt1+/- mice. Taken together, our data indicate that SIRT1 plays a pivotal role in muscle atrophy in CKD, and FoxO1 might be a substrate of SIRT1 in this process. Furthermore, resveratrol, together with other agonists of SIRT1, may hold great therapeutic potentials for treating CKD and its related muscle atrophy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-GAPDH antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL3265, purified immunoglobulin
Sigma-Aldrich
Anti-Sirt1 antibody, Mouse monoclonal, clone SIR11, purified from hybridoma cell culture
Sigma-Aldrich
Resveratrol, ≥99% (HPLC)