α MSH Blunts Endotoxin-Induced MuRF1 and Atrogin-1 Upregulation in Skeletal Muscle by Modulating NF- B and Akt/FoxO1 Pathway

Abstract

Alpha melanocyte stimulating hormone (α MSH) has been shown to have anti-inflammatory and anticachectic actions. We hypothesized that α 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 α MSH. α MSH administration reduced LPS-induced increase in liver TNF α 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 (P < 0.01). 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 α 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.