Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure.
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 (~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 O2consumption 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 & NOTEWORTHYResveratrol 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.
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Miranda M
MM
Sung
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Nikole J
NJ
Byrne
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Ian M
IM
Robertson
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Ty T
TT
Kim
Faculty of Pharmacy & Pharmaceutical Sciences, Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada.
Victor
V
Samokhvalov
Alberta Heart Failure Etiology and Analysis Research Team, Alberta Heritage Foundation for Medical Research Interdisciplinary Team Grant, Edmonton, Alberta, Canada.
Jody
J
Levasseur
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Carrie-Lynn
CL
Soltys
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
David
D
Fung
Department of Physical Education, University of Alberta, Edmonton, Alberta, Canada; and.
Neil
N
Tyreman
Department of Biochemistry and Biomedical Sciences and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Emmanuel
E
Denou
Department of Physical Education, University of Alberta, Edmonton, Alberta, Canada; and.
Kelvin E
KE
Jones
Faculty of Pharmacy & Pharmaceutical Sciences, Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada.
John M
JM
Seubert
Department of Biochemistry and Biomedical Sciences and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Jonathan D
JD
Schertzer
Faculty of Medicine and Dentistry, Department of Pediatrics, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; jason.dyck@ualberta.ca.|Alberta Heart Failure Etiology and Analysis Research Team, Alberta Heritage Foundation for Medical Research Interdisciplinary Team Grant, Edmonton, Alberta, Canada.
Jason R B
JR
Dyck
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects; D005221:Fatigue / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D018482:Muscle, Skeletal / Q000187:drug effects*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects
D000975:Antioxidants; D013267:Stilbenes; D005947:Glucose; D000077185:Resveratrol
exercise tolerance; gut microbiome; heart failure; resveratrol