macimorelin and Weight-Gain

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 weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous 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 (ED(50)=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 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight 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.

Topics: Adipose Tissue, Brown; Agouti-Related Protein; Animals; Appetite Stimulants; Dose-Response Relationship, Drug; Eating; Ghrelin; Hypothalamus; Indoles; Injections, Subcutaneous; Ion Channels; Male; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Neuropeptide Y; Oligopeptides; Receptors, Ghrelin; RNA, Messenger; Signal Transduction; Tryptophan; Uncoupling Protein 1; Up-Regulation; Weight Gain