α MSH Blunts Endotoxin-Induced MuRF1 and Atrogin-1 Upregulation in Skeletal Muscle by Modulating NF-κB and AktFoxO1 Pathway

Abstract EN

Alpha melanocyte stimulating hormone (αMSH) has been shown to have anti-inflammatory and anticachectic actions.

We hypothesized that αMSH 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 αMSH.

αMSH administration reduced LPS-induced increase in liver TNFα and serum nitrites as well as NF-κB 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-κB(p65), FoxO1, atrogin-1, and MuRF1 levels.

These results suggest that αMSH blunts skeletal muscle response to endotoxin by downregulating atrogenes and FoxO1 at least in part by controlling NF-κB activation and Akt signalling, but not through modifications in the secretion of corticosterone or IGF-I.