PKR modulates abnormal brain signaling in experimental obesity
| Autor: | Sarah Gourmaud, James A. R. Nicoll, Malha Sadoune, Jacques Hugon, Mariko Taga, Sylvie Thomasseau, Marion Tible, Jenny Norman, Claire Paquet, François Mouton-Liger, Delphine Boche |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine MAP Kinase Kinase 4 Physiology medicine.medical_treatment viruses lcsh:Medicine Type 2 diabetes Weight Gain Alzheimer's Disease Biochemistry environment and public health Mice eIF-2 Kinase Endocrinology 0302 clinical medicine Glucose Metabolism Medicine and Health Sciences Insulin lcsh:Science Mice Knockout Glucose tolerance test Multidisciplinary medicine.diagnostic_test Brain Neurodegenerative Diseases Inflammasome Animal Models I-kappa B Kinase Type 2 Diabetes Physiological Parameters Neurology Experimental Organism Systems Carbohydrate Metabolism medicine.symptom Signal Transduction Research Article medicine.drug medicine.medical_specialty Endocrine Disorders Mouse Models Inflammation Diet High-Fat Research and Analysis Methods 03 medical and health sciences Model Organisms Diabetes mellitus Internal medicine Mental Health and Psychiatry Diabetes Mellitus medicine Animals Obesity Triglycerides Diabetic Endocrinology business.industry Cholesterol HDL Body Weight lcsh:R Biology and Life Sciences Cholesterol LDL Glucose Tolerance Test medicine.disease Protein kinase R Hormones IRS1 Mice Inbred C57BL Metabolism 030104 developmental biology Gene Expression Regulation Metabolic Disorders Insulin Receptor Substrate Proteins Dementia lcsh:Q business 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE, Vol 13, Iss 5, p e0196983 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Metabolic disorders including obesity and type 2 diabetes are known to be associated with chronic inflammation and are obvious risk factors for Alzheimer’s disease. Recent evidences concerning obesity and diabetes suggest that the metabolic inflammasome (“metaflammasome”) mediates chronic inflammation. The double-stranded RNA-dependent protein kinase (PKR) is a central component of the metaflammasome. In wild type (WT) and PKR-/- mice, blood glucose, insulin and lipid levels and the brain expression of the phosphorylated components of the metaflammasome - PKR, JNK, IRS1 and IKKβ - were studied after the induction of obesity by a high fat diet (HFD). The results showed significant increased levels of activated brain metaflammasome proteins in exposed WT mice but the changes were not significant in PKR-/- mice. In addition, gain weight was observed in WT mice and also in PKR-/- mice exposed to HFD. Increased blood insulin level was more accentuated in PKR -/- mice. The modulation of PKR activity could be an appropriate therapeutic approach, aimed at reducing abnormal brain metabolism and inflammation linked to metabolic disorders in order to reduce the risk of neurodegeneration. |
| Databáze: | OpenAIRE |
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