𝛼MSH Blunts Endotoxin-Induced MuRF1 and Atrogin-1 Upregulation in Skeletal Muscle by Modulating NF-𝜅B and Akt/FoxO1 Pathway

Abstract

Alpha melanocyte stimulating hormone (MSH) has been shown to have anti-inflammatory and anticachectic actions. We hypothesized that MSH administration could attenuate the effect of lipopolysaccharide (LPS) on the skeletal muscle through modifications in IGF-Akt-FoxO1 pathway, or/and in serum corticosterone. Adult male Wistar rats were injected with LPS and/or MSH. MSH administration reduced LPS-induced increase in liver TNF and serum nitrites as well as NF-B activation in skeletal muscle. In contrast, αMSH was not able to prevent the stimulatory effect of LPS on serum concentration of ACTH and corticosterone. LPS decreased serum levels of IGF-I and IGFBP3 and their expression in the liver (). However IGFBP3 expression in the gastrocnemius was increased by LPS. Treatment with αMSH prevented the effects of LPS on IGFBP3 but not on IGF-I. In the gastrocnemius αMSH blocked LPS-induced decrease in pAkt as well as the increase in pNF-B(p65), FoxO1, atrogin-1, and MuRF1 levels. These results suggest that MSH blunts skeletal muscle response to endotoxin by downregulating atrogenes and FoxO1 at least in part by controlling NF-B activation and Akt signalling, but not through modifications in the secretion of corticosterone or IGF-I.