High fat suppresses SOD1 activity by reducing copper chaperone for SOD1 associated with neurodegeneration and memory decline.
High fat consumption leads to reactive oxygen species (ROS) which is associated with age-progressive neurological disorders. Cu/Zn superoxide dismutase (SOD1) is a critical enzyme against ROS. However, the relationship between SOD1 and the high-fat-induced ROS and neurodegeneration is poorly known. Here we showed that, upon treatment with a saturated fatty acid palmitic acid (PA), the SOD1 activity was decreased in mouse neuronal HT-22 cell line accompanied by elevation of ROS, but not in mouse microglial BV-2 cell line. We further showed that PA decreased the levels of copper chaperone for SOD1 (CCS) in HT-22 cells, which promoted the nuclear import of SOD1 and decreased its activity. We demonstrated that the reduction of CCS is involved in the PA-induced decrease of SOD1 activity and elevation of ROS. In addition, compared with the adult mice fed with a standard diet, the high-fat-diet adult mice presented an increase of plasma free fatty acids, reduction of hippocampal SOD1 activity and CCS, mitochondrial degeneration and long-term memory decline. Taken together, our findings suggest that the high-fat-induced lower CCS level is essential for SOD1 suppression which may be associated with neurodegeneration and cognitive decline.
['Lu|Ping|P|', 'Yan|Hua-Juan|HJ|', 'Yang|Cui|C|', 'Feng|Wen-Cai|WC|', 'Hu|Fei|F|', 'Wu|Yue-Ying|YY|', 'Sun|Wei-Wen|WW|', 'Gao|Mei-Mei|MM|', 'Long|Yue-Sheng|YS|']
D000818:Animals D002460:Cell Line D002681:China D003300:Copper D059305:Diet, High-Fat D008297:Male D008568:Memory D008569:Memory Disorders D051379:Mice D008810:Mice, Inbred C57BL D008928:Mitochondria D018832:Molecular Chaperones D019636:Neurodegenerative Diseases D019308:Palmitic Acid D017382:Reactive Oxygen Species D013482:Superoxide Dismutase D000072105:Superoxide Dismutase-1
High fat Reactive oxygen species (ROS) Cu/Zn superoxide dismutase (SOD1) Copper chaperone for SOD1 (CCS) Mitochondrial degeneration Learning and memory