title: Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting.
abstract: Rheumatoid cachexia is associated with rheumatoid arthritis and it increases mortality and morbidity. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that causes anorexia and muscle wasting. α-Melanocyte-stimulating hormone (α-MSH) has anti-inflammatory actions, and it is able to decrease inflammation in several inflammatory diseases including experimental arthritis. In this study we tested whether systemic α-MSH treatment is able to ameliorate cachexia in arthritic rats. On day 8 after adjuvant injection control and arthritic rats were treated with α-MSH (50 μg/rat ip) twice a day, until day 16 when all rats were euthanized. Arthritis decreased food intake, but it increased hypothalamic expression of neuropeptide Y (NPY) and Agouti-related peptides (AgRP) as well as interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) mRNA. In arthritic rats, α-MSH decreased the external signs of arthritis and increased food intake (P < 0.01). In addition, α-MSH decreased hypothalamic expression of IL-1β, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. In control rats, α-MSH did not modify food intake or hypothalamic expression of aforementioned mRNA. α-MSH prevented arthritis-induced increase in gastrocnemius COX-2, muscle-specific RING-finger protein-1 (MuRF1), and atrogin-1 expression, and it increased fast myofiber size. In conclusion our data show that in arthritic rats peripheral α-MSH treatment has an anti-cachectic action increasing food intake and decreasing muscle wasting.
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Gómez-SanMiguel
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Martín
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Nieto-Bona
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Galaz
authors.forename: María
authors.initials: M
authors.lastname: López-Menduiña
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Villanúa
authors.forename: Asunción
authors.initials: A
authors.lastname: López-Calderón
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000521:alpha-MSH / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D053583:Interleukin-1beta; D009478:Neuropeptide Y; D000521:alpha-MSH; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: COX-2; IL-10; IL-1β; adjuvant-induced arthritis; atrogin-1; food intake; muscle-specific RING-finger protein-1 1; proopiomelanocortin; ubiquitin-proteasome system