title: Gender differences of peripheral plasma and liver metabolic profiling in APP/PS1 transgenic AD mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment. Currently, there is less knowledge of the involvement of the peripheral biofluid/organ in AD, compared with the central nervous system. In addition, with reported high morbidity in women in particular, it has become very important to explore whether gender difference in the peripheral metabolome is associated with AD. Here, we investigated metabolic responses of both plasma and liver tissues using an APP/PS1 double mutant transgenic mouse model with NMR spectroscopy, as well as analysis from serum biochemistry and histological staining. Fatty acid composition from plasma and liver extracts was analyzed using GC-FID/MS. We found clear gender differences in AD transgenic mice when compared with their wild-type counterparts. Female AD mice displayed more intensive responses, which were highlighted by higher levels of lipids, 3-hydroxybutyrate and nucleotide-related metabolites, together with lower levels of glucose. These observations indicate that AD induces oxidative stress and impairs cellular energy metabolism in peripheral organs. Disturbances in AD male mice were milder with depletion of monounsaturated fatty acids. We also observed a higher activity of delta-6-desaturate and suppressed activity of delta-5-desaturate in female mice, whereas inhibited stearoyl-CoA-desaturase in male mice suggested that AD induced by the double mutant genes results in different fatty acids catabolism depending on gender. Our results provide metabolic clues into the peripheral biofluid/organs involved in AD, and we propose that a gender-specific scheme for AD treatment in men and women may be required.
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurology, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan 430015, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fu
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Hehua
authors.initials: H
authors.lastname: Lei
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Ministry of Education Key Laboratory of Contemporary Anthropology, Metabonomics and Systems Biology Laboratory, School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: huiru_tang@fudan.edu.cn.
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China. Electronic address: yulan.wang@wipm.ac.cn.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000502:physiology; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy; D012727:Sex Characteristics
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer’s disease; fatty acids; gender difference; liver extracts; metabonomics; peripheral