Interleukin 38 improves insulin resistance in hyperlipidemic skeletal muscle cells via PPARδ/SIRT1-mediated suppression of STAT3 signaling and oxidative stress

The cytokine interleukin-38 (IL-38), a recently discovered member of the IL-1 family, has been shown to regulate inflammation and improve hepatic endoplasmic reticulum stress and lipid metabolism in individuals with obesity. However, its impact on insulin signaling in skeletal muscle cells and the u...

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Veröffentlicht in:Biochemical and biophysical research communications 2024-08, Vol.722, p.150158, Article 150158
Hauptverfasser: Sun, Jaw Long, Kim, Young Jin, Cho, Wonjun, Lim, Do Su, Gwon, Hyeon Ji, Abd El-Aty, A.M., Nas, Mehmet Akif, Jeong, Ji Hoon, Jung, Tae Woo
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Sprache:eng
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Zusammenfassung:The cytokine interleukin-38 (IL-38), a recently discovered member of the IL-1 family, has been shown to regulate inflammation and improve hepatic endoplasmic reticulum stress and lipid metabolism in individuals with obesity. However, its impact on insulin signaling in skeletal muscle cells and the underlying mechanisms remain unclear. In vitro obesity models were established using palmitate treatment, and Western blot analysis was performed to assess target proteins. Commercial kits were used to measure glucose uptake in cultured myocytes. Our study showed that IL-38 treatment alleviated the impairment of insulin signaling, including IRS-1 and Akt phosphorylation, and increased glucose uptake in palmitate-treated C2C12 myocytes. Increased levels of STAT3-mediated signaling and oxidative stress were observed in these cells following palmitate treatment, and these effects were reversed by IL-38 treatment. In addition, IL-38 treatment upregulated the expression of PPARδ, SIRT1 and antioxidants. Knockdown of PPARδ or SIRT1 using appropriate siRNAs abrogated the effects of IL-38 on insulin signaling, oxidative stress, and the STAT3-dependent pathway. These results suggest that IL-38 alleviates insulin resistance by inhibiting STAT3-mediated signaling and oxidative stress in skeletal muscle cells through PPARδ/SIRT1. This study provides fundamental evidence to support the potential use of IL-38 as a safe therapeutic agent for the treatment of insulin resistance and type 2 diabetes. [Display omitted] •IL-38 attenuates palmitate-induced insulin resistance in C2C12 myocytes.•IL-38 suppresses STAT3 signaling and oxidative stress in palmitate-treated C2C12 myocytes.•IL-38 enhances PPARδ/SIRT1 pathway and augments antioxidants.•IL-38 improves insulin resistance in muscle cells via the PPARδ/SIRT1 pathway, reducing STAT3 signaling and oxidative stress.
ISSN:0006-291X
1090-2104
1090-2104
DOI:10.1016/j.bbrc.2024.150158