Hyperpolarized [1-13C] pyruvate MR spectroscopy detect altered glycolysis in the brain of a cognitively impaired mouse model fed high-fat diet

Abstract

Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p < 0.01) and increased conversion from pyruvate to lactate (p < 0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p < 0.01) and striatum (p < 0.05), while PDH activity was decreased in the cortex (p < 0.01) and striatum (p < 0.001) and the phosphorylated PDH was increased in the striatum (p < 0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p < 0.05). To determine whether hyperpolarized 13C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3 months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1-13C] pyruvate MR spectroscopy showed increased lactate conversion (P