RT Journal Article
T1 The melanocortin receptor type 3 agonist d-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats
A1 Gómez San Miguel, Ana Belén
A1 Martín Velasco, Ana Isabel
A1 Nieto Bona, María Paz
A1 Fernández Galaz, María Del Carmen
A1 Villanúa Bernués, María Ángeles
AB Background: 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.
PB Wiley
SN 2190-6009
YR 2015
FD 2015-05-11
LK https://hdl.handle.net/20.500.14352/88975
UL https://hdl.handle.net/20.500.14352/88975
LA eng
NO Gómez-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.
NO MINECO
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 7 abr 2025