Ghrelin agonist JMV 1843 increases food intake, body weight and expression of orexigenic neuropeptides in mice

Physiological Research (Prague, Czech Republic), Volume: 62, Issue: 4, Pages: 435-444, ISSN: 0862-8408

M. Holubova, A. Spolcova, Z. Demianova, D. Sykora, J. A. Fehrentz, J. Martinez, A. Stofkova, J. Jurcovicova, J. Drapalova, Z. Lacinova, M. Haluzik, B. Zelezna,  L. Maletinska


Ghrelin and agonists of its receptor GHS-R1a are potential substances for the treatment of cachexia.  In the present study, we investigated the acute and long-term effects of the GHS-R1a agonist JMV 1843 (H-Aib-DTrp-D-gTrp-CHO) on food intake, body wt. and metabolic parameters in lean C57BL/6 male mice.  Addnl., we examd. stability of JMV 1843 in mouse blood serum.  A single s.c. injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose-dependent manner, up to 5-times relative to the saline-treated group (ED50=1.94 mg/kg at 250 min).  JMV 1843 was stable in mouse serum in vitro for 24 h, but was mostly eliminated from mouse blood after 2 h in vivo.  Ten days of treatment with JMV 1843 (s.c. administration, 10 or 20 mg/kg/day) significantly increased food intake, body wt. and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hypothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue.  Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia.