title: Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa.
abstract: (-)-Epicatechin (Epi), a flavanol in cacao stimulates mitochondrial volume and cristae density and protein markers of skeletal muscle (SkM) mitochondrial biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are diseases associated with defects in SkM mitochondrial structure/function. A study was implemented to assess perturbations and to determine the effects of Epi-rich cocoa in SkM mitochondrial structure and mediators of biogenesis. Five patients with DM2 and stage II/III HF consumed dark chocolate and a beverage containing approximately 100 mg of Epi per day for 3 months. We assessed changes in protein and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin, nNOS, nitric oxide, cGMP, SIRT1, PGC1α, Tfam, and mitochondria volume and cristae abundance by electron microscopy from SkM. Apparent major losses in normal mitochondria structure were observed before treatment. Epi-rich cocoa increased protein and/or activity of mediators of biogenesis and cristae abundance while not changing mitochondrial volume density. Epi-rich cocoa treatment improves SkM mitochondrial structure and in an orchestrated manner, increases molecular markers of mitochondrial biogenesis resulting in enhanced cristae density. Future controlled studies are warranted using Epi-rich cocoa (or pure Epi) to translate improved mitochondrial structure into enhanced cardiac and/or SkM muscle function.
authors.affiliation: School of Medicine, University of California, San Diego, California, USA.
authors.forename: Pam R
authors.initials: PR
authors.lastname: Taub
authors.forename: Israel
authors.initials: I
authors.lastname: Ramirez-Sanchez
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Ciaraldi
authors.forename: Guy
authors.initials: G
authors.lastname: Perkins
authors.forename: Anne N
authors.initials: AN
authors.lastname: Murphy
authors.forename: Robert
authors.initials: R
authors.lastname: Naviaux
authors.forename: Michael
authors.initials: M
authors.lastname: Hogan
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos
authors.forename: Francisco
authors.initials: F
authors.lastname: Villarreal
mesh_terms: D000368:Aged; D001628:Beverages; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002099:Cacao; D002140:California; D002182:Candy; D002392:Catechin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055951:Functional Food; D006442:Glycated Hemoglobin / Q000378:metabolism; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002392:Catechin; D006442:Glycated Hemoglobin; D008055:Lipids; D024101:Mitochondrial Proteins; D020097:Natriuretic Peptide, Brain; C517652:hemoglobin A1c protein, human