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Gómez San Miguel, Ana Belén Villanúa Bernués, María Ángeles López-Calderón Barreda, Asunción Martín Velasco, Ana Isabel 2023-11-24T12:23:39Z 2023-11-24T12:23:39Z 2016 Gómez San Miguel, A. B., Villanúa Bernués, M. Á., López-Calderón Barreda, A. et al. «D-TRP(8)-γMSH Prevents the Effects of Endotoxin in Rat Skeletal Muscle Cells through TNFα/NF-KB Signalling Pathway». PLOS ONE, editado por Ashok Kumar, vol. 11, n.o 5, mayo de 2016, p. e0155645. https://doi.org/10.1371/journal.pone.0155645. 10.1371/journal.pone.0155645 https://hdl.handle.net/20.500.14352/88971 1932-6203 https://doi.org/10.1371/journal.pone.0155645 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155645 Sepsis induces anorexia and muscle wasting secondary to an increase in muscle proteolysis. Melanocyte stimulating hormones (MSH) is a family of peptides that have potent antiinflammatory effects. Melanocortin receptor-3 (MC3-R) has been reported as the predominant anti-inflammatory receptor for melanocortins. The aim of this work was to analyse whether activation of MC3-R, by administration of its agonist D-Trp(8)-γMSH, is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS) or TNFα. Adult male rats were injected with 250 μg/kg LPS and/or 500 μg/kg D-Trp(8)-γMSH 17:00 h and at 8:00 h the following day, and euthanized 4 hours afterwards. D-Trp(8)-γMSH decreased LPS-induced anorexia and prevented the stimulatory effect of LPS on hypothalamic IL-1β, COX-2 and CRH as well as on serum ACTH and corticosterone. Serum IGF-I and its expression in liver and gastrocnemius were decreased in rats injected with LPS, but not in those that also received D-Trp(8)-γMSH. However, D-Trp (8)-γMSH was unable to modify the effect of LPS on IGFBP-3. In the gastrocnemius D-Trp (8)-γMSH blocked LPS-induced decrease in pAkt, pmTOR, MHC I and MCH II, as well as the increase in pNF-κB(p65), FoxO1, FoxO3, LC3b, Bnip-3, Gabarap1, atrogin-1, MuRF1 and in LC3a/b lipidation. In L6 myotube cultures, D-Trp(8)-γMSH was able to prevent TNFαinduced increase of NF-κB(p65) phosphorylation and decrease of Akt phosphorylation as well as of IGF-I and MHC I expression. These data suggest that MC3-R activation prevents the effect of endotoxin on skeletal wasting by modifying inflammation, corticosterone and IGF-I responses and also by directly acting on muscle cells through the TNFα/NF-κB(p65) pathway eng open access D-TRP(8)-γMSH Prevents the Effects of Endotoxin in Rat Skeletal Muscle Cells through TNFα/NF-KB Signalling Pathway journal article