Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice

Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic bene...

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Main Authors: Yiwei Li, Zhi Yu, Yuanyuan Liu, Ting Wang, Yajuan Liu, Zhixia Bai, Yi Ren, Huiyan Ma, Ting Bao, Haixia Lu, Rui Wang, Libo Yang, Ning Yan, Ru Yan, Shaobin Jia, Xiaoxia Zhang, Hao Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2022.830781/full
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author Yiwei Li
Zhi Yu
Yuanyuan Liu
Ting Wang
Yajuan Liu
Yajuan Liu
Yajuan Liu
Zhixia Bai
Zhixia Bai
Zhixia Bai
Yi Ren
Huiyan Ma
Huiyan Ma
Huiyan Ma
Ting Bao
Haixia Lu
Rui Wang
Libo Yang
Libo Yang
Ning Yan
Ning Yan
Ru Yan
Ru Yan
Shaobin Jia
Shaobin Jia
Xiaoxia Zhang
Hao Wang
author_facet Yiwei Li
Zhi Yu
Yuanyuan Liu
Ting Wang
Yajuan Liu
Yajuan Liu
Yajuan Liu
Zhixia Bai
Zhixia Bai
Zhixia Bai
Yi Ren
Huiyan Ma
Huiyan Ma
Huiyan Ma
Ting Bao
Haixia Lu
Rui Wang
Libo Yang
Libo Yang
Ning Yan
Ning Yan
Ru Yan
Ru Yan
Shaobin Jia
Shaobin Jia
Xiaoxia Zhang
Hao Wang
author_sort Yiwei Li
collection DOAJ
description Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic Apolipoprotein E (ApoE)−/− mice. In the initial portion, the ApoE−/− mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated ApoE−/− mice were divided into two groups: AB-treated model group (AB/MOD) and FO-fed AB-treated model group (AB/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic/vascular inflammatory cytokines and in situ macrophages (Mψs) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in ApoE−/− mice via the gut microbiota-inflammation-artery axis.
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spelling doaj.art-de2e49174032490c8b325eb92be2a1d62022-12-21T19:29:08ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-02-01910.3389/fcvm.2022.830781830781Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− MiceYiwei Li0Zhi Yu1Yuanyuan Liu2Ting Wang3Yajuan Liu4Yajuan Liu5Yajuan Liu6Zhixia Bai7Zhixia Bai8Zhixia Bai9Yi Ren10Huiyan Ma11Huiyan Ma12Huiyan Ma13Ting Bao14Haixia Lu15Rui Wang16Libo Yang17Libo Yang18Ning Yan19Ning Yan20Ru Yan21Ru Yan22Shaobin Jia23Shaobin Jia24Xiaoxia Zhang25Hao Wang26School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaDepartment of Anesthesiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, ChinaSchool of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaSchool of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaClinical Medical College, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaClinical Medical College, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaClinical Medical College, Ningxia Medical University, Yinchuan, ChinaClinical Medical College, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaClinical Medical College, Ningxia Medical University, Yinchuan, ChinaDepartment of Anesthesiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, ChinaClinical Medical College, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaDepartment of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, ChinaCollege of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, ChinaSchool of Basic Medical Sciences, Ningxia Medical University, Yinchuan, ChinaAtherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic Apolipoprotein E (ApoE)−/− mice. In the initial portion, the ApoE−/− mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated ApoE−/− mice were divided into two groups: AB-treated model group (AB/MOD) and FO-fed AB-treated model group (AB/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic/vascular inflammatory cytokines and in situ macrophages (Mψs) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in ApoE−/− mice via the gut microbiota-inflammation-artery axis.https://www.frontiersin.org/articles/10.3389/fcvm.2022.830781/fullALA-rich flaxseed oilatherosclerosisinflammationgut microbiotaintestinal metabolites
spellingShingle Yiwei Li
Zhi Yu
Yuanyuan Liu
Ting Wang
Yajuan Liu
Yajuan Liu
Yajuan Liu
Zhixia Bai
Zhixia Bai
Zhixia Bai
Yi Ren
Huiyan Ma
Huiyan Ma
Huiyan Ma
Ting Bao
Haixia Lu
Rui Wang
Libo Yang
Libo Yang
Ning Yan
Ning Yan
Ru Yan
Ru Yan
Shaobin Jia
Shaobin Jia
Xiaoxia Zhang
Hao Wang
Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice
Frontiers in Cardiovascular Medicine
ALA-rich flaxseed oil
atherosclerosis
inflammation
gut microbiota
intestinal metabolites
title Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice
title_full Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice
title_fullStr Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice
title_full_unstemmed Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice
title_short Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice
title_sort dietary α linolenic acid rich flaxseed oil ameliorates high fat diet induced atherosclerosis via gut microbiota inflammation artery axis in apoe mice
topic ALA-rich flaxseed oil
atherosclerosis
inflammation
gut microbiota
intestinal metabolites
url https://www.frontiersin.org/articles/10.3389/fcvm.2022.830781/full
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