Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting

Am J Physiol Regul Integr Comp Physiol. 2013 May 15;304(10):R877-86. doi: 10.1152/ajpregu.00447.2012. Epub 2013 Mar 20.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / metabolism
  • Animals
  • Anorexia / drug therapy*
  • Anorexia / etiology
  • Anorexia / metabolism
  • Arthritis, Experimental / complications
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Cachexia / drug therapy*
  • Cachexia / etiology
  • Cachexia / metabolism
  • Cyclooxygenase 2 / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Neuropeptide Y / metabolism
  • Rats
  • Rats, Wistar
  • alpha-MSH / pharmacology
  • alpha-MSH / therapeutic use*


  • AGRP protein, rat
  • Agouti-Related Protein
  • Interleukin-1beta
  • Neuropeptide Y
  • alpha-MSH
  • Cyclooxygenase 2
  • Ptgs2 protein, rat