Toyama Kensuke, Koibuchi Nobutaka, Hasegawa Yu, Uekawa Ken, Yasuda Osamu, Sueta Daisuke, Nakagawa Takashi, Ma Mingjie, Kusaka Hiroaki, Lin Bowen, Ogawa Hisao, Ichijo Hidenori, Kim-Mitsuyama Shokei
Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Kumamoto.
Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto.
Sci Rep. 2015 Jun 5;5:10844. doi: 10.1038/srep10844.
Although high-fat diet intake is known to cause obesity and diabetes, the effect of high-fat diet itself on cognitive function remains to be clarified. We have previously shown that apoptosis signal-regulating kinase 1 (ASK1) is responsible for cognitive impairment caused by chronic cerebral hypoperfusion. The present work, by using ASK1 deficient mice, was undertaken to explore the influence of chronic high-fat diet intake on cognitive function and the role of ASK1. Cognitive function in wild-type mice fed high-fat diet from 2 to 24 months of age was significantly impaired compared to those fed control diet, which was associated with the significant white matter lesions, reduction of hippocampal capillary density, and decrement of hippocampal neuronal cell. However, ASK1 deficiency abolished the development of cognitive impairment and cerebral injury caused by high-fat diet. Our results provided the evidence that high-fat diet itself causes cognitive impairment and ASK1 participates in such cognitive impairment.
尽管已知高脂饮食会导致肥胖和糖尿病，但高脂饮食本身对认知功能的影响仍有待阐明。我们之前已经表明，凋亡信号调节激酶1（ASK1）是慢性脑灌注不足所致认知障碍的原因。本研究利用ASK1基因敲除小鼠，探讨长期高脂饮食对认知功能的影响以及ASK1的作用。与喂食对照饮食的野生型小鼠相比，2至24月龄喂食高脂饮食的野生型小鼠的认知功能显著受损，这与明显的白质病变、海马毛细血管密度降低以及海马神经元细胞减少有关。然而，ASK1基因缺失消除了高脂饮食所致的认知障碍和脑损伤的发展。我们的结果证明，高脂饮食本身会导致认知障碍，且ASK1参与了这种认知障碍。
