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The Peptidic GHS-R antagonist [D-Lys(3)]GHRP-6 markedly improves adiposity and related metabolic abnormalities in a mouse model of postmenopausal obesity
L. Maletínská, R. Matyšková, J. Maixnerová, D. Sýkora, M. Pýchová, A. Spolcová, M. Blechová, J. Drápalová, Z. Lacinová, M. Haluzík, B. Zelezná,
Language English Country Ireland
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Adiposity drug effects MeSH
- Behavior, Animal drug effects MeSH
- Diet, High-Fat MeSH
- Estrogens administration & dosage deficiency MeSH
- Ghrelin metabolism MeSH
- Adipose Tissue, Brown metabolism MeSH
- Ion Channels genetics metabolism MeSH
- Humans MeSH
- Mitochondrial Proteins genetics metabolism MeSH
- Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Obesity physiopathology MeSH
- Oligopeptides pharmacology MeSH
- Ovariectomy MeSH
- Motor Activity drug effects MeSH
- Postmenopause metabolism MeSH
- PPAR alpha genetics metabolism MeSH
- Glucose Transporter Type 1 genetics metabolism MeSH
- Eating drug effects MeSH
- Receptors, Ghrelin antagonists & inhibitors genetics metabolism MeSH
- Body Weight drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
References provided by Crossref.org
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