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

Abstract(-)-Epicatechin (Epi), a fl avanol 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, mitofi lin, nNOS, nitric oxide, cGMP, SIRT1, PGC1␣, 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.

(–)-Epicatechin Suppresses Angiotensin II-induced Cardiac Hypertrophy via the Activation of the SP1/SIRT1 Signaling Pathway

“…The protective effect of EPI may occur via a reduction in oxidative stress, and improvement of mitochondrial structure and function [15-17]. Previous studies have also revealed that EPI-rich cocoa treatment improved mitochondrial structure and enhanced cardiac and/or SkM muscle function in patients with heart failure [18]. Furthermore, some studies have indicated that the epicatechin conjugate (EGCG) can alleviate cardiomyocyte hypertrophy [30-32].…”

“…EPI treatment also improved mitochondrial structure in enhanced cardiac and/or SkM muscle function in patients with heart failure. Moreover, EPI increased the protein expression of SIRT1 [18]. Taken together, these results indicate a beneficial role for EPI in cardioprotective function and specifically in the protection of heart failure.…”

Mitochondrial Quality Control as a Therapeutic Target

“…In humans (Taub et al, 2012), the administration of an epicatechin-rich cocoa (total epicatechin was 100 mg/day during 3 months) to patients with type 2 diabetes and heart failure stimulates mitochondrial biogenesis in skeletal muscle biopsies, as expressed by an increment in SIRT1-dependent activation of PGC-1a and as an elevation in mitofilin, porin, and mitochondrial complexes I and V protein levels. The long-term effect of curcumin, a dietary polyphenol derived from turmeric has been investigated on various markers of mitochondrial biogenesis.…”

Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy

“…They showed that the beneficial effect of epicatechin could be due in part to protection of mitochondria (36). Huttemann et al (18) also recently reported that epicatechin could maintain exercise-induced mitochondrial capacity in the hindlimb muscles of mice even after discontinuation of exercise.…”

“…Recently, Villarreal's research group (28,31,32,36,41,42) has examined the effects of epicatechin in the setting of cardiovascular disease. They showed that the beneficial effect of epicatechin could be due in part to protection of mitochondria (36).…”