Počet záznamů: 1

Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity

SYSNO ASEP	0443999
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity
Tvůrce(i)	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, ORCID}
Celkový počet autorů	10
Zdroj.dok.	Journal of Alzheimer's Disease. - : IOS Press - ISSN 1387-2877 Roč. 45, č. 3 (2015), s. 823-835
Poč.str.	13 s.
Jazyk dok.	eng - angličtina
Země vyd.	NL - Nizozemsko
Klíč. slova	Alzheimer's disease ; insulin signaling ; liraglutide ; monosodium glutamate-obese mice ; obesity ; pre-diabetes ; prolactin-releasing peptide
Vědní obor RIV	CE - Biochemie
CEP	GAP303/12/0576 GA ČR - Grantová agentura ČR
Institucionální podpora	UOCHB-X - RVO:61388963
UT WOS	000351608700013
EID SCOPUS	84925821657
DOI	10.3233/JAD-143150
Anotace	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.
Pracoviště	Ústav organické chemie a biochemie
Kontakt	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Rok sběru	2016

Počet záznamů: 1