Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity
| Autor: | Martin Haluzik, Marie-Christine Galas, Blanka Železná, Jana Zemenová, Lenka Maletínská, Zdenko Pirnik, Martina Holubová, Barbora Mikulášková, Andrea Špolcová, Veronika Nagelová |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Time Factors Monosodium glutamate medicine.medical_treatment [SDV]Life Sciences [q-bio] [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Insulins Hippocampus Receptors G-Protein-Coupled chemistry.chemical_compound Mice 0302 clinical medicine Glucagon-Like Peptide 1 Sodium Glutamate Phosphorylation ComputingMilieux_MISCELLANEOUS 0303 health sciences Prolactin-Releasing Hormone biology Kinase General Neuroscience General Medicine 3. Good health Psychiatry and Mental health Clinical Psychology medicine.drug Signal Transduction medicine.medical_specialty Tau protein tau Proteins 03 medical and health sciences Lipopeptides Internal medicine medicine Animals Obesity Protein kinase B 030304 developmental biology Analysis of Variance business.industry Liraglutide Insulin Body Weight Glucose Tolerance Test Flavoring Agents Insulin receptor Disease Models Animal Endocrinology chemistry biology.protein Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease Journal of Alzheimer's Disease, IOS Press, 2015, 45 (3), pp.823-835. ⟨10.3233/JAD-143150⟩ |
| ISSN: | 1387-2877 |
| DOI: | 10.3233/JAD-143150⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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