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

作者：Isabel Martin Ana; Belen Gomez SanMiguel Ana; Gomez Moreira Carolina; Angeles Villanua Maria; Lopez Calderon Asuncion^*

来源：Mediators of Inflammation, 2014, 2014: 179368.

DOI：10.1155/2014/179368

Alpha melanocyte stimulating hormone (alpha MSH) has been shown to have anti-inflammatory and anticachectic actions. We hypothesized that alpha 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 alpha MSH. alpha MSH administration reduced LPS-induced increase in liver TNF alpha and serum nitrites as well as NF-kappa B activation in skeletal muscle. In contrast, alpha MSH 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 alpha MSH prevented the effects of LPS on IGFBP3 but not on IGF-I. In the gastrocnemius alpha MSH blocked LPS-induced decrease in pAkt as well as the increase in pNF-kappa B(p65), FoxO1, atrogin-1, and MuRF1 levels. These results suggest that alpha MSH blunts skeletal muscle response to endotoxin by downregulating atrogenes and FoxO1 at least in part by controlling NF-kappa B activation and Akt signalling, but not through modifications in the secretion of corticosterone or IGF-I.

• 出版日期2014