期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 312, 期 4, 页码 H842-H853出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00455.2016
关键词
exercise tolerance; gut microbiome; heart failure; resveratrol
资金
- Canadian Institute of Health Research (CIHR)
- Natural Sciences and Engineering Research Council of Canada
- Neuromuscular Research Partnership
- Alberta Innovates Health Services
- Motyl Studentship in Cardiac Sciences from the University of Alberta
- Alberta Innovates-Health Solutions
- CIHR New Investigator awards [MSH-136665]
- Alberta Innovates [201500030, 201600257] Funding Source: researchfish
We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (% ejection fraction <45) was administered resveratrol (similar to 450 mg.kg(-1).day(-1)) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O-2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients. NEW & NOTEWORTHY Resveratrol treatment of mice with heart failure leads to enhanced exercise performance that is associated with altered gut microbiota composition, increased whole body glucose utilization, and enhanced skeletal muscle metabolism and function. Together, these preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in heart failure via these mechanisms.
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