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

Daussin, Frédéric N.; Cuillerier, Alexane; Touron, Julianne; Bensaid, Samir; Melo, Berildo de; Rewashdy, Ali Al; Vasam, Goutham; Menzies, Keir J.; Harper, Mary‐Ellen; Heyman, Elsa; Burelle, Yan

doi:10.3390/nu13103466

Cited by 6 publications

(5 citation statements)

References 73 publications

(106 reference statements)

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“…Oral administration of NAD + precursors, such as tryptophan, nicotinic acid (niacin), nicotinamide, and nicotinamide riboside (NR), could increase tissue NAD + levels 525 , 526 . Food supplement cocoa flavanol is shown to boost the NAD + and NADH content, stimulate sirtuin metabolism, reduce cellular H 2 O 2 production as well as OxS, and improve mitochondrial function in PASC patients 527 . Increasing NAD + levels could also stabilize telomeres and help recovery of elderly PASC patients 528 .…”

Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

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Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

View full text Add to dashboard Cite

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“…A recent study has reported that epicatechin reduced the cardiac fibrosis in an aged female rat model of pre-heart failure, which correlates with significant reductions in oxidative stress and cytokine levels in the absence of changes in contractile function [130]. Another study by Daussin et al [131] also showed that the administration of cocoa flavanols to mice for 15 days stimulated the NAD metabolism which enhanced the SIRT metabolism and improved the mitochondrial function [131]. In addition, supplementation with a cocoa-carob blend diet rich in flavanols to Zucker diabetic fatty rats counteracted the oxidative stress in diabetic hearts by downregulating the NADPH oxidases, reducing the ROS generation, and modulating the SIRT1/Nrf2 signaling pathway, overall improving the antioxidant defense.…”

Section: Recent Advances In Cocoa Flavanols On Nrf2 Pathway/antioxida...mentioning

confidence: 96%

From Cocoa to Chocolate: Effect of Processing on Flavanols and Methylxanthines and Their Mechanisms of Action

Goya

Kongor

Pascual‐Teresa

2022

IJMS

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Despite the health benefits associated with the ingestion of the bioactive compounds in cocoa, the high concentrations of polyphenols and methylxanthines in the raw cocoa beans negatively influence the taste, confer the astringency and bitterness, and affect the stability and digestibility of the cocoa products. It is, therefore, necessary to process cocoa beans to develop the characteristic color, taste, and flavor, and reduce the astringency and bitterness, which are desirable in cocoa products. Processing, however, affects the composition and quantities of the bioactive compounds, resulting in the modification of the health-promoting properties of cocoa beans and chocolate. In this advanced review, we sought to better understand the effect of cocoa’s transformational process into chocolate on polyphenols and methylxanthine and the mechanism of action of the original flavanols and methylxanthines. More data on the cocoa processing effect on cocoa bioactives are still needed for better understanding the effect of each processing step on the final polyphenolic and methylxanthine composition of chocolate and other cocoa products. Regarding the mechanisms of action, theobromine acts through the modulation of the fatty acid metabolism, mitochondrial function, and energy metabolism pathways, while flavanols mainly act though the protein kinases and antioxidant pathways. Both flavanols and theobromine seem to be involved in the nitric oxide and neurotrophin regulation.

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“…One of the primary targets of SIRT3 deacetylase is metabolism-associated proteins. Studies using SIRT3 knockout mice suggest that SIRT3 has a prominent role in maintaining metabolism homeostasis [ 47 , 85 , 86 , 87 ]. In fact, SIRT3 is heavily involved in various physiological metabolic processes through deacetylation, and thus involved in the process of several diseases of aging, including cancer, heart diseases, metabolic diseases, etc.…”

Section: The Effects Of Sirt3 On Agingmentioning

confidence: 99%

The Role of SIRT3 in Exercise and Aging

Zhou

Pinho

et al. 2022

Cells

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The health benefits of regular exercise are well established. Nonetheless, the molecular mechanism(s) responsible for exercise-induced health benefits remain a topic of debate. One of the key cell-signaling candidates proposed to provide exercise-induced benefits is sirtuin 3 (SIRT3). SIRT3, an NAD+ dependent mitochondrial deacetylase, positively modulates many cellular processes, including energy metabolism, mitochondrial biogenesis, and protection against oxidative stress. Although the exercise-induced change in SIRT3 signaling is a potential mechanism contributing to the health advantages of exercise on aging, studies investigating the impact of exercise on SIRT3 abundance in cells provide conflicting results. To resolve this conundrum, this narrative review provides a detailed analysis of the role that exercise-induced changes in SIRT3 play in providing the health and aging benefits associated with regular physical activity. We begin with an overview of SIRT3 function in cells followed by a comprehensive review of the impact of exercise on SIRT3 expression in humans and other mammalians. We then discuss the impact of SIRT3 on aging, followed by a thorough analysis of the cell-signaling links between SIRT3 and exercise-induced adaptation. Notably, to stimulate future research, we conclude with a discussion of key unanswered questions related to exercise, aging, and SIRT3 expression.

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

Cited by 6 publications

References 73 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

From Cocoa to Chocolate: Effect of Processing on Flavanols and Methylxanthines and Their Mechanisms of Action

The Role of SIRT3 in Exercise and Aging

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