Anorexigenic lipopeptides ameliorate central insulin signaling and attenuate tau phosphorylation in hippocampi of mice with monosodium glutamate-induced obesity
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25624414
DOI
10.3233/jad-143150
PII: D0843686074J7946
Knihovny.cz E-resources
- Keywords
- Alzheimer's disease, insulin signaling, liraglutide, monosodium glutamate-obese mice, obesity, pre-diabetes, prolactin-releasing peptide, tau phosphorylation,
- MeSH
- Analysis of Variance MeSH
- Time Factors MeSH
- Flavoring Agents toxicity MeSH
- Phosphorylation drug effects MeSH
- Glucagon-Like Peptide 1 genetics pharmacology MeSH
- Glucose Tolerance Test MeSH
- Sodium Glutamate toxicity MeSH
- Hippocampus drug effects metabolism MeSH
- Prolactin-Releasing Hormone drug effects pharmacology MeSH
- Insulins metabolism MeSH
- Lipopeptides metabolism therapeutic use MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Obesity * chemically induced drug therapy pathology MeSH
- tau Proteins metabolism MeSH
- Receptors, G-Protein-Coupled metabolism MeSH
- Signal Transduction drug effects MeSH
- Body Weight drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Flavoring Agents MeSH
- Glucagon-Like Peptide 1 MeSH
- Sodium Glutamate MeSH
- Prolactin-Releasing Hormone MeSH
- Insulins MeSH
- Lipopeptides MeSH
- tau Proteins MeSH
- Receptors, G-Protein-Coupled 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
References provided by Crossref.org
NPFFR2-deficient mice fed a high-fat diet develop strong intolerance to glucose
Prolactin-Releasing Peptide: Physiological and Pharmacological Properties
