Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, β-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease
| Autor: | Anjelica C. Saulsberry, Shilpy Dixit, James M. May, Fiona E. Harrison, Jennifer M. Walker |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse medicine.medical_specialty Calorie Inflammatory response Mice Transgenic Disease Diet High-Fat Article lcsh:RC321-571 Inflammatory response β-amyloid high fat diet Amyloid beta-Protein Precursor 03 medical and health sciences Cognition 0302 clinical medicine Alzheimer Disease Weight loss Internal medicine Presenilin-1 medicine PSEN1 Animals Cognitive Dysfunction Obesity Cognitive decline lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Behavior Memory Disorders Amyloid beta-Peptides medicine.disease Mice Inbred C57BL Disease Models Animal Glucose 030104 developmental biology Endocrinology Neurology Female medicine.symptom Psychology 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Disease, Vol 100, Iss, Pp 87-98 (2017) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2017.01.004 |
| Popis: | This study assessed the extent to which high fat diet (HFD)-induced β-amyloid accumulation and cognitive decline in APP/PSEN1 mice are reversible through control of fat intake. Ten months of HFD (60% calories from fat) led to significant deficits in a 2-trial Y maze task, and nest building assay, and decreased voluntary locomotor activity. The HFD induced an inflammatory response, indicated by increased expression of several inflammatory markers. Substituting a low fat diet led to pronounced weight loss and correction of glucose intolerance, decreases in the inflammatory response, and improved performance on behavioral tasks in both wild-type and APP/PSEN1 transgenic mice. Insoluble β-amyloid levels, and extent of tau phosphorylation were also lower following dietary reversal in APP/PSEN1 mice compared to high fat-fed animals, indicating that the inflammatory response may have contributed to key pathogenic pathways in the Alzheimer's disease model. The data suggest that weight loss can be a vital strategy for cognitive protection, but also highlight potential mechanisms for intervention when sustained weight loss is not possible. |
| Databáze: | OpenAIRE |
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