title: (-)-Epicatechin is associated with increased angiogenic and mitochondrial signalling in the hindlimb of rats selectively bred for innate low running capacity.
abstract: Alternative approaches to reduce congenital muscle dysfunction are needed in cases where the ability to exercise is limited. (-)-Epicatechin is found in cocoa and may stimulate capillarity and mitochondrial proliferation in skeletal muscle. A total of 21 male rats bred for LCR (low running capacity) from generation 28 were randomized into three groups: vehicle for 30 days (control); (-)-epicatechin for 30 days; and (-)-epicatechin for 30 days followed by 15 days without (-)-epicatechin. Groups 2 and 3 received 1.0 mg of (-)-epicatechin/kg of body mass twice daily, whereas water was given to the control group. The plantaris muscle was harvested for protein and morphometric analyses. In addition, in vitro experiments were conducted to examine the role of (-)-epicatechin on mitochondrial respiratory kinetics at different incubation periods. Treatment for 30 days with (-)-epicatechin increased capillarity (P<0.001) and was associated with increases in protein expression of VEGF (vascular endothelial growth factor)-A with a concomitant decrease in TSP-1 (thrombospondin-1) and its receptor, which remained after 15 days of (-)-epicatechin cessation. Analyses of the p38 MAPK (mitogen-activated protein kinase) signalling pathway indicated an associated increase in phosphorylation of MKK3/6 (MAPK kinase 3/6) and p38 and increased protein expression of MEF2A (myocyte enhancer factor 2A). In addition, we observed significant increases in protein expression of PGC-1α (peroxisome-proliferator-activated receptor γ co-activator 1α), PGC-1β, Tfam and cristae abundance. Interestingly, these increases associated with (-)-epicatechin treatment remained after 15 days of cessation. Lastly, in vitro experiments indicated that acute exposure of LCR muscle to (-)-epicatechin incubation was not sufficient to increase mitochondrial respiration. The results suggest that increases in skeletal muscle capillarity and mitochondrial biogenesis are associated with 30 days of (-)-epicatechin treatment and sustained for 15 days following cessation of treatment. Clinically, the use of this natural compound may have potential application in populations that experience muscle fatigue and are unable to perform endurance exercise.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.forename: Icksoo
authors.initials: I
authors.lastname: Lee
authors.forename: Guy A
authors.initials: GA
authors.lastname: Perkins
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.forename: Moh H
authors.initials: MH
authors.lastname: Malek
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D051928:CD47 Antigen / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D006614:Hindlimb / Q000378:metabolism; D007700:Kinetics; D026161:MADS Domain Proteins / Q000378:metabolism; D048371:MAP Kinase Kinase 3 / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D064326:MEF2 Transcription Factors; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D010807:Physical Endurance; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D012420:Running / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D019700:Thrombospondin 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D018955:CD36 Antigens; D051928:CD47 Antigen; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578037:MEF2A protein, rat; D018006:Myogenic Regulatory Factors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D019700:Thrombospondin 1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D002392:Catechin; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6