title: Ghrelin agonist JMV 1843 increases food intake, body weight and expression of orexigenic neuropeptides in mice.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic. maletin@uochb.cas.cz
authors.forename: M
authors.initials: M
authors.lastname: Holubová
authors.forename: A
authors.initials: A
authors.lastname: Spolcová
authors.forename: Z
authors.initials: Z
authors.lastname: Demianová
authors.forename: D
authors.initials: D
authors.lastname: Sýkora
authors.forename: J A
authors.initials: JA
authors.lastname: Fehrentz
authors.forename: J
authors.initials: J
authors.lastname: Martinez
authors.forename: A
authors.initials: A
authors.lastname: Stofková
authors.forename: J
authors.initials: J
authors.lastname: Jurčovičová
authors.forename: J
authors.initials: J
authors.lastname: Drápalová
authors.forename: Z
authors.initials: Z
authors.lastname: Lacinová
authors.forename: M
authors.initials: M
authors.lastname: Haluzík
authors.forename: B
authors.initials: B
authors.lastname: Zelezná
authors.forename: L
authors.initials: L
authors.lastname: Maletínská
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019167:Appetite Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D054439:Ghrelin / Q000819:agonists* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles; D007279:Injections, Subcutaneous; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014364:Tryptophan / Q000031:analogs & derivatives; D000071256:Uncoupling Protein 1; D015854:Up-Regulation; D015430:Weight Gain / Q000187:drug effects*
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D019167:Appetite Stimulants; D054439:Ghrelin; D007211:Indoles; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D009842:Oligopeptides; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C582727:macimorelin; D014364:Tryptophan