Research has already established that a high-fat diet is unhealthy for many reasons; however, new research conducted by scientists from Australia and China published in Metabolic Brain Disease in June indicated that fatty foods may contribute to cognitive deficits and exacerbate depression-like behavior.
According to Associate Professor Larisa Bobrovskaya, author of the study and University of South Australia neuroscientist and biochemist, her team's research will augment the currently evolving body of evidence that links metabolic diseases like diabetes and obesity to Alzheimer's disease (AD)—which to date, has no cure—while worldwide diagnoses only continue to grow as the population ages. Although obesity is a consequence of excess calories from all sources not otherwise burned, high-fat foods may be especially problematic.
The research team set out to provide a mouse model that mimics AD patients with obesity and type 2 diabetes (T2DM) for use in studies of "the relationships between AD, T2DM and obesity, and the underlying biological changes and mechanisms associated with metabolic disorders and AD tauopathy." They randomly assigned pR5 mice expressing P301L mutant human tau and C57BL/6 (WT) mice at age 8 weeks to either a standard diet (STD) or high-fat diet (HFD) for 30 weeks.
Measurements of food intake were performed weekly, and measurements of body weight and fasting glucose levels were performed every 2 weeks. There was also a comprehensive test battery to assess anxiety, depression, and cognitive dysfunction. After 30 weeks of a HFD, glucose and insulin tolerance tests were conducted. Western blotting of the whole brain homogenates for total tau, phosphorylated tau at Ser396, and Thr231 was performed to determine the impact of HFD on tau pathology in the brains of both mice groups.
The study results indicated that the pR5 mice, compared with the WT mice, were more vulnerable to diet-induced obesity, with greater discrepancies as they aged. The results also indicated that pR5 mice developed glucose intolerance on a HFD and exhibited behavior consistent with depression and impaired cognitive function when on a long-term HFD. The researchers observed changes to tau hyperphosphorylation in what they labeled the "pR5 transgenic mice." The authors stated that the results support their goal of developing a mouse model that mimics AD patients with obesity and T2DM that will be useful in future studies.
The pR5 mice display worsened glucose tolerance compared with obese WT mice despite similar body weight, fat mass, and total time on the HFD. "Obese individuals have about a 55% increased risk of developing depression, and diabetes will double that risk," Dr. Bobrovskaya stated.
Additionally, Dr. Bobrovskaya proclaimed, "Our findings underline the importance of addressing the global obesity epidemic. A combination of obesity, age and diabetes is very likely to lead to a decline in cognitive abilities, Alzheimer's disease, and other mental health disorders." She elaborated further, "Obesity and diabetes impair the central nervous system, exacerbating psychiatric disorders and cognitive decline. We demonstrated this in our study with mice."
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