Mechanism of high-fat diet causing metabolic cognitive decline in lipid metabolism disorders

Abstract Recent findings support the notion that High fat homeostasis can cause dementia progressively. We investigate the relationship between glucose intolerance and cognitive impairment. Increasing body weights with high fat diet in transgenic mice in which the low-density-lipoprotein receptor (LDLr) was deleted, induce the glucose intolerance. This metabolic disorder for long period make the integrity of blood-brain barrier on hippocampal region disrupt and cognitive impairment. Cognitive dysfunction includes decreased short-term and working memory and motor functioning. Fasting blood glucose due to high fat intake in transgenic mice in which the low-density-lipoprotein receptor (LDLr) was deleted, and traced the association between metabolic disorders and the blood-brain barrier, and the alignment and integrity of the hippocampal region. And we tried to confirm the changes in motor ability and cognitive function through behavioral analysis. Therefore, this study investigated the effects of high-fat diet exposure on cognitive function, motor performance, blood-brain barrier (BBB) integrity, and hippocampal array changes in transgenic mice with ablated LDLR receptor (LDLr). We also wanted to determine changes the adverse effects of these changes on the development of dementia caused by a high-fat diet. It was confirmed that stabilization and permeability of the BBB structure deteriorated due to a high-fat diet, and genes expressed in precursors for neurogenesis were reduced. The BBB regulates the transport of molecules into the central nervous system (CNS) maintaining tight control over the chemical composition of the nervous environment required for proper nerve function. In this sense, it can be hypothesized that high-fat diet-induced BBB dysfunction alters the neurogenic environment contributing to cognitive impairment. Changes in the BBB structure resulted in weakening of the cortical and hippocampal arrangements, and prolonged high-fat diets resulted in general motor and cognitive dysfunction.