Muscle-specific deletion of SOCS3 does not reduce the anabolic response to leucine in a mouse model of acute inflammation. (August 2017)

• Record Type: Journal Article
• Authors: Caldow, M.K.; Ham, D.J.; Chee, A.; Trieu, J.; Naim, T.; Stapleton, D.I.; Swiderski, K.; Lynch, G.S.; Koopman, R.
• Is Part Of: Cytokine. Volume 96(2017)
• Page Start: 274
• Page End: 278
• Publication Date: 2017-08
• Subjects: SOCS3-MKO SOCS3 muscle-specific knockout -- LPS lipopolysaccharide; SOCS3 -- Inflammation -- Anabolic signaling -- Protein synthesis; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2017.05.016
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: SOCS3 deletion in skeletal muscle does not alter LPS-induced inflammation. SOCS3 does not mediate the anabolic response to leucine in skeletal muscle. Leucine augments the LPS-induced expression of IL-6 and STAT3 phosphorylation. Abstract: Excessive inflammation reduces skeletal muscle protein synthesis leading to wasting and weakness. The janus kinase/signal transducers and activators of transcription-3 (JAK/STAT3) pathway is important for the regulation of inflammatory signaling. As such, suppressor of cytokine signaling-3 (SOCS3), the negative regulator of JAK/STAT signaling, is thought to be important in the control of muscle homeostasis. We hypothesized that muscle-specific deletion of SOCS3 would impair the anabolic response to leucine during an inflammatory insult. Twelve week old (n = 8 per group) SOCS3 muscle-specific knockout mice (SOCS3-MKO) and littermate controls (WT) were injected with lipopolysaccharide (LPS, 1 mg/kg) or saline and were studied during fasted conditions or after receiving 0.5 g/kg leucine 3 h after the injection of LPS. Markers of inflammation, anabolic signaling, and protein synthesis were measured 4 h after LPS injection. LPS injection robustly increased mRNA expression of inflammatory molecules ( Socs3, Socs1, Il-6, Ccl2, Tnfα and Cd68 ). In muscles from SOCS3-MKO mice, the Socs3 mRNA response to LPS was significantly blunted (∼6-fold) while STAT3 Tyr705 phosphorylation was exacerbated (18-fold). Leucine administration increased protein synthesis in both WT (∼1.6-fold) and SOCS3-MKO mice (∼1.5-fold) compared to basal levels. LPS administration blunted this effect, but there were no differences between WT and SOCS3-MKO mice. Muscle-specific SOCS3 deletion did not alter the response of AKT, mTOR, S6 or 4EBP1 under any treatment conditions. Therefore, SOCS3 does not appear to mediate the early inflammatory or leucine-induced changes in protein synthesis in skeletal muscle.