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Anorexigenic lipopeptides ameliorate central insulin signaling and attenuate tau phosphorylation in hippocampi of mice with monosodium glutamate-induced obesity
A. Špolcová, B. Mikulášková, M. Holubová, V. Nagelová, Z. Pirnik, J. Zemenová, M. Haluzík, B. Železná, MC. Galas, L. Maletínská,
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25624414
DOI
10.3233/jad-143150
Knihovny.cz E-zdroje
- MeSH
- analýza rozptylu MeSH
- časové faktory MeSH
- chuťové esence toxicita MeSH
- fosforylace účinky léků MeSH
- glukagonu podobný peptid 1 genetika farmakologie MeSH
- glukózový toleranční test MeSH
- glutamát sodný toxicita MeSH
- hipokampus účinky léků metabolismus MeSH
- hormon uvolňující prolaktin účinky léků farmakologie MeSH
- inzuliny metabolismus MeSH
- lipopeptidy metabolismus terapeutické užití MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- obezita * chemicky indukované farmakoterapie patologie MeSH
- proteiny tau metabolismus MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- signální transdukce účinky léků MeSH
- tělesná hmotnost účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Numerous epidemiological and experimental studies have demonstrated that patients who suffer from metabolic disorders, such as type 2 diabetes mellitus (T2DM) or obesity, have higher risks of cognitive dysfunction and of Alzheimer's disease (AD). Impaired insulin signaling in the brain could contribute to the formation of neurofibrillary tangles, which contain an abnormally hyperphosphorylated tau protein. This study aimed to determine whether potential tau hyperphosphorylation could be detected in an obesity-induced pre-diabetes state and whether anorexigenic agents could affect this state. We demonstrated that 6-month-old mice with monosodium glutamate (MSG) obesity, which represent a model of obesity-induced pre-diabetes, had increased tau phosphorylation at Ser396 and Thr231 in the hippocampus compared with the controls, as determined by western blots. Two weeks of subcutaneous treatment with a lipidized analog of prolactin-releasing peptide (palm-PrRP31) or with the T2DM drug liraglutide, which both had a central anorexigenic effect, resulted in increased phosphorylation of the insulin cascade kinases PDK1 (Ser241), Akt (Thr308), and GSK-3β (Ser9). Furthermore, these drugs attenuated phosphorylation at Ser396, Thr231, and Thr212 of tau and of the primary tau kinases in the hippocampi of 6-month-old MSG-obese mice. We identified tau hyperphosphorylation in the obesity-induced pre-diabetes state in MSG-obese mice and demonstrated the beneficial effects of palm-PrRP31 and liraglutide, both of known central anorexigenic effects, on hippocampal insulin signaling and on tau phosphorylation.
3rd Department of Medicine 1st Faculty of Medicine Charles University Prague Prague Czech Republic
Institute of Organic Chemistry and Biochemistry AS CR Prague Czech Republic
Citace poskytuje Crossref.org
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