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Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice.

ABSTRACT: Mitochondrial dysfunction is widely reported in various diseases and contributes to their pathogenesis. We assessed the effect of cocoa flavanols supplementation on mitochondrial function and whole metabolism, and we explored whether the mitochondrial deacetylase sirtuin-3 (Sirt3) is involved or not. We explored the effects of 15 days of CF supplementation in wild type and Sirt3-/- mice. Whole-body metabolism was assessed by indirect calorimetry, and an oral glucose tolerance test was performed to assess glucose metabolism. Mitochondrial respiratory function was assessed in permeabilised fibres and the pyridine nucleotides content (NAD+ and NADH) were quantified. In the wild type, CF supplementation significantly modified whole-body metabolism by promoting carbohydrate use and improved glucose tolerance. CF supplementation induced a significant increase of mitochondrial mass, while significant qualitative adaptation occurred to maintain H2O2 production and cellular oxidative stress. CF supplementation induced a significant increase in NAD+ and NADH content. All the effects mentioned above were blunted in Sirt3-/- mice. Collectively, CF supplementation boosted the NAD metabolism that stimulates sirtuins metabolism and improved mitochondrial function, which likely contributed to the observed whole-body metabolism adaptation, with a greater ability to use carbohydrates, at least partially through Sirt3.

SUBMITTER: Daussin FN

PROVIDER: S-EPMC8538722 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice.

Daussin Frédéric Nicolas FN Cuillerier Alexane A Touron Julianne J Bensaid Samir S Melo Bruno B Al Rewashdy Ali A Vasam Goutham G Menzies Keir J KJ Harper Mary-Ellen ME Heyman Elsa E Burelle Yan Y

Nutrients 20210929 10

Mitochondrial dysfunction is widely reported in various diseases and contributes to their pathogenesis. We assessed the effect of cocoa flavanols supplementation on mitochondrial function and whole metabolism, and we explored whether the mitochondrial deacetylase sirtuin-3 (Sirt3) is involved or not. We explored the effects of 15 days of CF supplementation in wild type and Sirt3<sup>-/-</sup> mice. Whole-body metabolism was assessed by indirect calorimetry, and an oral glucose tolerance test was ...[more]

PMID: 34684467

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Project description:Background and objectivesHemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD.Design, setting, participants, & measurementsWe conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics.ResultsCF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01).ConclusionsDietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD.

Project description:IntroductionCocoa flavanols (CF) may exert health benefits through their potent vasodilatory effects, which are perpetuated by elevations in nitric oxide (NO) bioavailability. These vasodilatory effects may contribute to improved delivery of blood and oxygen (O2) to exercising muscle.PurposeTherefore, the objective of this study was to examine how CF supplementation impacts pulmonary O2 uptake ([Formula: see text]) kinetics and exercise tolerance in sedentary middle-aged adults.MethodsWe employed a double-blind cross-over, placebo-controlled design whereby 17 participants (11 male, 6 female; mean ± SD, 45 ± 6 years) randomly received either 7 days of daily CF (400 mg) or placebo (PL) supplementation. On day 7, participants completed a series of 'step' moderate- and severe-intensity exercise tests for the determination of [Formula: see text] kinetics.ResultsDuring moderate-intensity exercise, the time constant of the phase II [Formula: see text] kinetics ([Formula: see text]) was decreased by 15% in CF as compared to PL (mean ± SD; PL 40 ± 12 s vs. CF 34 ± 9 s, P = 0.019), with no differences in the amplitude of [Formula: see text] (A[Formula: see text]; PL 0.77 ± 0.32 l min-1 vs. CF 0.79 ± 0.34 l min-1, P = 0.263). However, during severe-intensity exercise, [Formula: see text], the amplitude of the slow component ([Formula: see text]) and exercise tolerance (PL 435 ± 58 s vs. CF 424 ± 47 s, P = 0.480) were unchanged between conditions.ConclusionOur data show that acute CF supplementation enhanced [Formula: see text] kinetics during moderate-, but not severe-intensity exercise in middle-aged participants. These novel effects of CFs, in this demographic, may contribute to improved tolerance of moderate-activity physical activities, which appear commonly present in daily life.Trial registrationRegistered under ClinicalTrials.gov Identifier no. NCT04370353, 30/04/20 retrospectively registered.

Dataset Information

Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice.

Publications

Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice.

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