Abstract
The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates. Regular physical activity is an effective strategy for maintaining endothelial health and function to prevent the development of atherosclerosis. Obesity is also a crucial risk factor for atherosclerotic progression in combination with various complications and systemic inflammation. Physiological homeostasis is modulated by the intestinal microbiota, but the mechanisms through which exercise attenuates atherosclerosis through the microbiota have not been elucidated. Therefore, we investigated the effects of endurance exercise on atherosclerosis induced by a Western diet (WD) and apolipoprotein E (ApoE) knockout in terms of microbiota parameters and metabolites. Genetically modified ApoE knockout mice (C57BL/6-Apoeem1Narl/Narl, ApoEKO) and wild-type mice (C57BL6/J) were divided into the following four groups (n = 6), namely, wild-type mice fed a chow diet (WT CD), ApoEKO mice fed a chow diet (ApoE CD), ApoEKO mice fed a WD (ApoE WD), and ApoEKO mice fed a WD and performing endurance exercise (ApoE WD EX), for a 12-week intervention. The WD significantly induced obesity and atherosclerotic syndrome in the ApoE WD group. Severe atherosclerotic lesions and arterial thickness were significantly elevated and accompanied by increases in VCAM-1, MCP-1, TNF-α, and IL-1β for immune cell chemotaxis and inflammation during atherosclerotic pathogenesis in the ApoE WD group. In addition, dysbiosis in the ApoE WD group resulted in the lowest short-chain fatty acid (SCFA) production. Endurance exercise intervention (ApoE WD EX) significantly alleviated atherosclerotic syndrome by reducing obesity, significantly inhibiting VCAM-1, MCP-1, TNF-α, and IL-1β expression, and increasing the production of SCFAs. Modulation of the microbiota associated with inflammation, such as Desulfovibrio, Tyzzerella, and Lachnospiraceae_ge, and increased SCFA production, particularly through an abundance of Rikenellaceae and Dubosiella, were also observed after exercise intervention. Endurance exercise can alleviate WD-induced atherosclerosis through the amelioration of obesity, inflammation, and chemotaxis signaling, which are modulated by the microbiota and derived SCFAs.
Highlights
The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates
The body weight and blood lipid profiles of the wild-type mice fed a chow diet (WT CD), apolipoprotein E (ApoE) CD, ApoE Western diet (WD), and ApoE WD EX groups exhibited significant differences after 3 months (Table 1); significant differences in the initial body weight, cholesterol, and triacylglycerol were observed among groups (F(3,20) = 4.25, P = 0.018; F(3,20) = 29.1, P < 0.0001; F(3,20) = 10.1, P < 0.0001, respectively) before the WD dietary and exercise intervention
The body weight in the ApoE CD group was significantly higher than those in the WT CD and ApoE WD groups before intervention, but no significant difference was noted among the WT CD, ApoE WD, and ApoE WD EX groups
Summary
The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates. We investigated the effects of endurance exercise on atherosclerosis induced by a Western diet (WD) and apolipoprotein E (ApoE) knockout in terms of microbiota parameters and metabolites. Endurance exercise can alleviate WD-induced atherosclerosis through the amelioration of obesity, inflammation, and chemotaxis signaling, which are modulated by the microbiota and derived SCFAs. Abbreviations ApoEKO ApoE genetical knockout CVDs Cardiovascular diseases HDL High-density lipoprotein cholesterol LDA Linear discriminant analysis LDL Low-density lipoprotein cholesterol LEfSe Linear discriminant analysis effect size MCP-1 Monocyte chemoattractant protein-1 PcoA Principal co-ordinates analysis SCFAs Short chain fatty acids TNF-α Tumor necrosis factor alpha VCAM-1 Vascular cell adhesion protein 1 WD Western diet DECIPHER Database of Genomic Variation and Phenotype in Humans Using Ensemble Resources. Regular aerobic exercise, such as running or swimming, provides physiological benefits that potentially minimize the risk of obesity-associated atherosclerosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
