title: ASK1 is involved in cognitive impairment caused by long-term high-fat diet feeding in mice.
abstract: 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.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Toyama
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Ken
authors.initials: K
authors.lastname: Uekawa
authors.affiliation: Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Kumamoto.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sueta
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Mingjie
authors.initials: M
authors.lastname: Ma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kusaka
authors.forename: Bowen
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
authors.forename: Hidenor
authors.initials: H
authors.lastname: Ichijo
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D066127:White Matter / Q000378:metabolism / Q000473:pathology
chemical_list: D052242:Adiponectin; D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha; D019255:NADPH Oxidases; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse