Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model

Abstract Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-...

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Main Authors: Yu Fujita, Kuniyuki Kano, Shigenobu Kishino, Toshihiro Nagao, Xuefeng Shen, Chiharu Sato, Hatsune Hatakeyama, Yume Ota, Sho Niibori, Ayako Nomura, Kota Kikuchi, Wataru Yasuno, Sho Takatori, Kazunori Kikuchi, Yoshitake Sano, Taisuke Tomita, Toshiharu Suzuki, Junken Aoki, Kun Zou, Shunji Natori, Hiroto Komano
Format: Article
Language:English
Published: Nature Publishing Group 2021-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-88870-9
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spelling doaj-fb153ff6b32e481daa74b997a95644a62021-05-16T11:24:22ZengNature Publishing GroupScientific Reports2045-23222021-05-0111111310.1038/s41598-021-88870-9Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse modelYu Fujita0Kuniyuki Kano1Shigenobu Kishino2Toshihiro Nagao3Xuefeng Shen4Chiharu Sato5Hatsune Hatakeyama6Yume Ota7Sho Niibori8Ayako Nomura9Kota Kikuchi10Wataru Yasuno11Sho Takatori12Kazunori Kikuchi13Yoshitake Sano14Taisuke Tomita15Toshiharu Suzuki16Junken Aoki17Kun Zou18Shunji Natori19Hiroto Komano20Division of Neuroscience, School of Pharmacy, Iwate Medical UniversityLaboratory of Molecular and Cellular Biochemistry, Graduates School of Pharmaceutical Sciences, Tohoku UniversityDivision of Applied Life Sciences, Graduate School of Agriculture, Kyoto UniversityOsaka Research Institute of Industrial Science and Technology, Morinomiya CenterDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityInstitute for Biomedical Sciences, Library, Iwate Medical UniversityLaboratory of Neuropathology and Neuroscience, Graduates School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, The University of TokyoLaboratory of Neuropathology and Neuroscience, Graduates School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, The University of TokyoDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of ScienceLaboratory of Neuropathology and Neuroscience, Graduates School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, The University of TokyoLaboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityLaboratory of Molecular and Cellular Biochemistry, Graduates School of Pharmaceutical Sciences, Tohoku UniversityDepartment of Biochemistry, School of Medicine, Nagoya City UniversityGraduates School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, University of TokyoDivision of Neuroscience, School of Pharmacy, Iwate Medical UniversityAbstract Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.https://doi.org/10.1038/s41598-021-88870-9
collection DOAJ
language English
format Article
sources DOAJ
author Yu Fujita
Kuniyuki Kano
Shigenobu Kishino
Toshihiro Nagao
Xuefeng Shen
Chiharu Sato
Hatsune Hatakeyama
Yume Ota
Sho Niibori
Ayako Nomura
Kota Kikuchi
Wataru Yasuno
Sho Takatori
Kazunori Kikuchi
Yoshitake Sano
Taisuke Tomita
Toshiharu Suzuki
Junken Aoki
Kun Zou
Shunji Natori
Hiroto Komano
spellingShingle Yu Fujita
Kuniyuki Kano
Shigenobu Kishino
Toshihiro Nagao
Xuefeng Shen
Chiharu Sato
Hatsune Hatakeyama
Yume Ota
Sho Niibori
Ayako Nomura
Kota Kikuchi
Wataru Yasuno
Sho Takatori
Kazunori Kikuchi
Yoshitake Sano
Taisuke Tomita
Toshiharu Suzuki
Junken Aoki
Kun Zou
Shunji Natori
Hiroto Komano
Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
Scientific Reports
author_facet Yu Fujita
Kuniyuki Kano
Shigenobu Kishino
Toshihiro Nagao
Xuefeng Shen
Chiharu Sato
Hatsune Hatakeyama
Yume Ota
Sho Niibori
Ayako Nomura
Kota Kikuchi
Wataru Yasuno
Sho Takatori
Kazunori Kikuchi
Yoshitake Sano
Taisuke Tomita
Toshiharu Suzuki
Junken Aoki
Kun Zou
Shunji Natori
Hiroto Komano
author_sort Yu Fujita
title Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
title_short Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
title_full Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
title_fullStr Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
title_full_unstemmed Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model
title_sort dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an alzheimer’s disease mouse model
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-05-01
description Abstract Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.
url https://doi.org/10.1038/s41598-021-88870-9
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