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Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity
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SYSNO ASEP 0443999 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity Author(s) Špolcová, Andrea (UOCHB-X) RID, ORCID
Mikulášková, Barbora (UOCHB-X)
Holubová, Martina (UOCHB-X) RID, ORCID
Nagelová, Veronika (UOCHB-X) RID, ORCID
Pirník, Zdenko (UOCHB-X)
Zemenová, Jana (UOCHB-X)
Haluzík, M. (CZ)
Železná, Blanka (UOCHB-X) RID, ORCID
Galas, M. C. (FR)
Maletínská, Lenka (UOCHB-X) RID, ORCIDNumber of authors 10 Source Title Journal of Alzheimer's Disease. - : IOS Press - ISSN 1387-2877
Roč. 45, č. 3 (2015), s. 823-835Number of pages 13 s. Language eng - English Country NL - Netherlands Keywords Alzheimer's disease ; insulin signaling ; liraglutide ; monosodium glutamate-obese mice ; obesity ; pre-diabetes ; prolactin-releasing peptide Subject RIV CE - Biochemistry R&D Projects GAP303/12/0576 GA ČR - Czech Science Foundation (CSF) Institutional support UOCHB-X - RVO:61388963 UT WOS 000351608700013 EID SCOPUS 84925821657 DOI 10.3233/JAD-143150 Annotation 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-3 beta (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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2016
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