Impact of Highly Palatable Diet on Brain Metabolism In vivo

Introduction: Obesity is currently a global public health issue, and its association with several pathological conditions is well known. Recent epidemiological data indicate it as an important risk factor for developing neurodegenerative diseases, such as Alzheimer's Disease (AD). However, the pathological mechanisms that connect these two conditions are still elusive. Evidence points towards glucose metabolism dysregulation, as well as defective insulin signaling, and peripheral and central inflammation. OBJECTIVES: Our main goal is to use a mice model fed with a highly palatable (HP) diet to study brain glucose metabolism with 18F-fluorodeoxiglucose ([18F]FDG) positron emission microtomography (microPET), a widely used marker of neurodegeneration in AD patients. Materials and methods: Male C57BL/6J mice (45 days old) were fed HP diet (rich in simple sugars and fat) for four months. They were then examined using [18F]FDG microPET neuroimaging. Data from images were used to assemble [18F]FDG-derived brain metabolic network. A glucose tolerance test (GTT) was performed to assess peripheral insulin response. Post-mortem, the brain tissue was used in a high resolution respirometry test for mitochondrial activity. Discussion and results: HP diet animals present increased body weight and abnormal tolerance to glucose (indexed by GTT). HP diet also induced [18F]FDG hypermetabolism in the prefrontal cortex and hypersynchronicity in the metabolic network with hypothalamus being highly connected to the hippocampus, thalamus, prefrontal cortex, and striatum. Brain post-mortem analysis indicates a less efficient mitochondrial oxidative phosphorylation in HP diet fed animals. Conclusion: These preliminary results show that HP diet causes peripheral and central disturbances in the glucose metabolism, with altered brain mitochondrial activity. Interestingly, In vivo imaging indicates that prefrontal cortex is highly active and the hypothalamus is highly connected in HP diet fed animals.