title: The Peptidic GHS-R antagonist [D-Lys(3)]GHRP-6 markedly improves adiposity and related metabolic abnormalities in a mouse model of postmenopausal obesity.
abstract: It was demonstrated that estrogen deficiency and consuming high fat (HF) diet enhanced orexigenic activity of ghrelin. Therefore, we hypothesized that antagonizing of ghrelin action would attenuate food intake and body weight in mice obese both from ovariectomy (OVX) and feeding a HF diet. Ghrelin receptor antagonist [D-Lys(3)]GHRP-6 after seven days of subcutaneous treatment markedly decreased food intake in OVX mice fed both HF and standard diets; furthermore, it reduced body weight and blood glucose, insulin and leptin, and increased β-hydroxybutyrate level and uncoupling-protein-1 mRNA in brown adipose tissue. Pair-feeding revealed that effect of [D-Lys(3)]GHRP-6 was primary anorexigenic. Estrogen supplementation reduced anorexigenic effects of [D-Lys(3)]GHRP-6. OVX [D-Lys(3)]GHRP-6 treatment in mice on HF diet resulted in markedly increased circulating level and liver expression of a major metabolic regulator, fibroblast growth factor 21. Our data suggest that ghrelin antagonists could be especially beneficial in individuals with common obesity combined with estrogen deficiency.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic. maletin@uochb.cas.cz
authors.forename: L
authors.initials: L
authors.lastname: Maletínská
authors.forename: R
authors.initials: R
authors.lastname: Matyšková
authors.forename: J
authors.initials: J
authors.lastname: Maixnerová
authors.forename: D
authors.initials: D
authors.lastname: Sýkora
authors.forename: M
authors.initials: M
authors.lastname: Pýchová
authors.forename: A
authors.initials: A
authors.lastname: Spolcová
authors.forename: M
authors.initials: M
authors.lastname: Blechová
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
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D004967:Estrogens / Q000008:administration & dosage / Q000172:deficiency; D005260:Female; D054439:Ghrelin / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000503:physiopathology*; D009842:Oligopeptides / Q000494:pharmacology*; D010052:Ovariectomy; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D017698:Postmenopause / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D004967:Estrogens; D054439:Ghrelin; D051272:Glucose Transporter Type 1; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009842:Oligopeptides; D047493:PPAR alpha; D054440:Receptors, Ghrelin; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C041048:growth hormone releasing hexapeptide