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Long term high fat diet induces metabolic disorders and aggravates behavioral disorders and cognitive deficits in MAPT P301L transgenic mice
Alzheimer’s disease (AD) is an uncommon condition that usually occurs late in life, a condition where several metabolic factors were found to contribute to its onset and course. Peripheral tissue insulin resistance and pathologies observed in tau proteins were demonstrated through studies of diabetes employing streptozotocin-injected and db/db mouse models. In their study, Xiong et al. (2022) fed pR5 mice (exhibiting P301L mutant human tau) a high-fat diet (HFD) in their attempt to create and characterize a new mouse model for the study of obesity, Type-II Diabetes Mellitus (T2DM) and AD, aimed to mirror AD patients whose clinical course is worsened by obesity and diabetes, two pervasive conditions in our modern society. Eight-week-old pR5 and C57BL/6 (wild type – WT) mice were given either a standard diet (STD) or HFD for a period of 30 weeks, during which their food consumption and weight were measured weekly, while their fasting glucose levels were recorded every fortnight. The mice were subjected to a series of behavioral tests to determine their depression, anxiety, and cognitive function statuses. Finally, insulin tolerance and glucose levels were investigated after 30 weeks of HFD, and tau protein pathology was investigated in both WT and P301L mice. Analysis of the results demonstrated that HFD led to enhancing obesity in pR5 mice compared to WTs and that this effect was more profound as the mice got older. Secondly, HFD increased glucose intolerance and insulin resistance, in addition to substantially worsening cognitive function and well-being (evident by increased depressive and anxiety-like behavior) in pR5 and WT mice. Finally, an increase in tau hyperphosphorylation in pR5 mice and overall total and hyperphosphorylated tau in WT mice was observed in long-term exposure to HFD, a known mechanism of AD pathology. The authors conclude that their results show the impact of obesity on pR5 transgenic mice expressing mutant human tau P301L in developing T2DM and enhancing tau phosphorylation, thus proving the model a viable platform to explore the links between AD, obesity, and T2DM, in addition to the biochemical and the mechanistic factors that govern AD tauopathies and metabolic diseases. [NPID: Alzheimer’s disease, high fat diet, obesity, T2DM, tauopathy]
Year: 2022
