LAUSR

HighlightsSOCS3 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, Tnf&agr; 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.