Gómez San Miguel, Ana BelénMartín Velasco, Ana IsabelNieto Bona, María PazFernández Galaz, María Del CarmenVillanúa Bernués, María Ángeles2023-11-242023-11-242015-05-11Gómez-SanMiguel AB, Martín AI, Nieto-Bona MP, Fernández-Galaz C, Villanúa MÁ, López-Calderón A. The melanocortin receptor type 3 agonist d-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats. J Cachexia Sarcopenia Muscle. 2016 Mar;7(1):79-89. doi: 10.1002/jcsm.12036. Epub 2015 May 11. PMID: 27066320; PMCID: PMC4799854.2190-600910.1002/jcsm.12036https://hdl.handle.net/20.500.14352/88975Background: Chronic inflammatory diseases induce cachexia that increases mortality and morbidity of the illness. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. Alpha-melanocyte stimulating hormone has an anti-inflammatory effect in arthritic rats and decreases muscle wasting. The aim of this work was to elucidate whether the anti-cachectic action of alpha-melanocyte stimulating hormone is mediated by the melanocortin receptor type 3 pathway. Methods: Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant, and 6 days afterwards, arthritic rats were injected with the selective melanocortin receptor type 3 agonist d-Trp(8)-gammaMSH ( d-Trp(8)-γMSH) 500 µg/kg subcutaneously. or saline twice a day, for 10 days. Results: d-Trp(8)-γMSH decreased the external signs of inflammation and body weight loss, but it was not able to modify the anorexigenic effect of arthritis or the increase in hypothalamic cyclooxygenase-2 (COX-2) expression. In contrast, d-Trp(8)-γMSH prevented arthritis-induced increase in hypothalamic IL-1β and serum corticosterone levels and the decrease in serum IGF-I levels. d-Trp(8)-γMSH treatment also prevented arthritis-induced NF-kB(p65) phosphorylation and tumour necrosis factor-α mRNA increase in the gastrocnemius. d-Trp(8)-γMSH administration to arthritic rats increased gastrocnemius mass, its cross-sectional area, and mean fast fibre area. Those effects of d-Trp(8)-γMSH were associated with a decreased expression of atrogin-1 and muscle ring-finger protein-1 in the gastrocnemius. In rats treated with saline, arthritis increased the expression of autophagy marker genes LC3b, Bnip-3, and Gabarap1 as well as the conversion of LC3b I to LC3b II by lipidation in the gastrocnemius. d-Trp(8)-γMSH decreased gastrocnemius LC3b, Bnip-3, and Gabarap1 mRNA expression and prevented the increase in LC3b II in arthritic rats. Conclusion: These data suggest that d-Trp(8)-γMSH administration prevents the effect of arthritis on corticosterone and insulin-like growth factor-I serum levels and decreases muscle wasting, by down-regulating atrogenes and autophagy through modifying the NF-kB(p65)/tumour necrosis factor-α signalling transduction pathway.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://onlinelibrary.wiley.com/journal/1353921906009open access612AtrogenesAutophagyCorticosteroneIGF‐IMuscle wastingNF‐kBγMSHFisiología32 Ciencias Médicas