The Peptidic GHS-R antagonist [D-Lys(3)]GHRP-6 markedly improves adiposity and related metabolic abnormalities in a mouse model of postmenopausal obesity
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21704671
DOI
10.1016/j.mce.2011.06.006
PII: S0303-7207(11)00314-5
Knihovny.cz E-resources
- 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
- Uncoupling Protein 1 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
- Names of Substances
- Estrogens MeSH
- Ghrelin MeSH
- growth hormone releasing hexapeptide MeSH Browser
- Ion Channels MeSH
- Mitochondrial Proteins MeSH
- Oligopeptides MeSH
- PPAR alpha MeSH
- Glucose Transporter Type 1 MeSH
- Receptors, Ghrelin MeSH
- UCP1 protein, human MeSH Browser
- Ucp1 protein, mouse MeSH Browser
- Uncoupling Protein 1 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.
Mol Cell Endocrinol. 2012 Jan 2;348(1):344 PubMed
References provided by Crossref.org
NPFFR2-deficient mice fed a high-fat diet develop strong intolerance to glucose
