title: (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle.
abstract: The flavanol (-)-epicatechin, a component of cacao (cocoa), has been shown to have multiple health benefits in humans. Using 1-year-old male mice, we examined the effects of 15 days of (-)-epicatechin treatment and regular exercise on: (1) exercise performance, (2) muscle fatigue, (3) capillarity, and (4) mitochondrial biogenesis in mouse hindlimb and heart muscles. Twenty-five male mice (C57BL/6N) were randomized into four groups: (1) water, (2) water-exercise (W-Ex), (3) (-)-epicatechin ((-)-Epi), and (4) (-)-epicatechin-exercise ((-)-Epi-Ex). Animals received 1 mg kg(-1) of (-)-epicatechin or water (vehicle) via oral gavage (twice daily). Exercise groups underwent 15 days of treadmill exercise. Significant increases in treadmill performance (∼50%) and enhanced in situ muscle fatigue resistance (∼30%) were observed with (-)-epicatechin. Components of oxidative phosphorylation complexes, mitofilin, porin, nNOS, p-nNOS, and Tfam as well as mitochondrial volume and cristae abundance were significantly higher with (-)-epicatechin treatment for hindlimb and cardiac muscles than exercise alone. In addition, there were significant increases in skeletal muscle capillarity. The combination of (-)-epicatechin and exercise resulted in further increases in oxidative phosphorylation-complex proteins, mitofilin, porin and capillarity than (-)-epicatechin alone. These findings indicate that (-)-epicatechin alone or in combination with exercise induces an integrated response that includes structural and metabolic changes in skeletal and cardiac muscles resulting in greater endurance capacity. These results, therefore, warrant the further evaluation of the underlying mechanism of action of (-)-epicatechin and its potential clinical application as an exercise mimetic.
authors.affiliation: Department of Medicine, School of Medicine, University of California, San Diego, CA, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nogueira
authors.forename: Israel
authors.initials: I
authors.lastname: Ramirez-Sanchez
authors.forename: Guy A
authors.initials: GA
authors.lastname: Perkins
authors.forename: Anne
authors.initials: A
authors.lastname: Murphy
authors.forename: Pam R
authors.initials: PR
authors.lastname: Taub
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Villarreal
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Moh H
authors.initials: MH
authors.lastname: Malek
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002196:Capillaries / Q000033:anatomy & histology; D002392:Catechin / Q000494:pharmacology*; D006614:Hindlimb; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000648:ultrastructure; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010805:Physical Conditioning, Animal / Q000502:physiology
chemical_list: D000975:Antioxidants; D002392:Catechin