title: Elevation of cortical C26:0 due to the decline of peroxisomal β-oxidation potentiates amyloid β generation and spatial memory deficits via oxidative stress in diabetic rats.
abstract: Diabetes mellitus correlates with subsequent development of Alzheimer's disease (AD). An accumulation of very long chain fatty acids (VLCFAs) was observed in AD brains. We found previously that inhibiting peroxisomal β-oxidation by an inhibitor caused increases in VLCFA and β-amyloid peptide (Aβ) in the cortex and primary cultured neurons of rats. Therefore, we investigated whether there was an impaired peroxisomal β-oxidation and elevated VLCFA related to the increased Aβ in the diabetic brain. This study was conducted in a type 2 diabetic rat model induced by a high-fat diet and low-dose streptozotocin. A decrease in peroxisomal β-oxidation activity caused by down-regulated thiolase expression and a consequent increase in C26:0 were observed. Meanwhile, decreases in eicosapentenoic acid (EPA) and increases in oxidative stress [indicated by levels of malondialdehyde (MDA), and the protein expression of NOX4, p47(phox) and HO-1], Aβ, and the expression of AβPP and BACE1, two proteins involved in Aβ production, were observed. C26:0 levels were positively correlated with Aβ and MDA. This work suggests that in addition to decreases in EPA, increases in C26:0 by impaired peroxisomal β-oxidation can be a potential risk factor contributing to the progression of AD in diabetic brains via inducing oxidative stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: L
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: M
authors.initials: M
authors.lastname: Yao
authors.affiliation: The School of Public Health, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: K
authors.initials: K
authors.lastname: Lian
authors.affiliation: Hebei People's Hospital, Shijiazhuang 050051, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: jianglingling1959@163.com.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000523:psychology; D003924:Diabetes Mellitus, Type 2; D005227:Fatty Acids / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008562:Membrane Glycoproteins; D008569:Memory Disorders / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1; D065852:Spatial Memory / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D005227:Fatty Acids; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D008315:Malondialdehyde; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Alzheimer’s disease; oxidative stress; peroxisomal β-oxidation; type 2 diabetes mellitus; very long chain fatty acid