Branched chain amino acids selectively promote cardiac growth at the end of the awake period

Latimer, Mary N.; Sonkar, Ravi; Mia, Sobuj; Frayne, Isabelle Robillard; Carter, Karen J.; Johnson, Christopher; Rana, Samir; Xie, Min; Rowe, Glenn C.; Wende, Adam R.; Prabhu, Sumanth D.; Frank, Stuart J.; Rosiers, Christine Des; Chatham, John C.; Young, Martin E.

doi:10.1016/j.yjmcc.2021.04.005

Cited by 34 publications

(38 citation statements)

References 48 publications

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“…These have reported significant age-related changes such as alterations in beta-oxidation mechanisms, with significantly lower levels of acylcarnitines, dysregulation of the TCA cycle, and a higher abundance of proteins involved in the process of glycolysis/gluconeogenesis such as glucose-6-phosphate and fructose-6-phosphate [ 67 , 68 ]. Nevertheless, our results report additional differences between the two groups not reported previously to be influenced by age, highlighting the increased concentrations of aspartate and the lower concentrations of BCAAs, as reports in the literature have suggested higher levels of BCAAs with increasing age, leading to activation of mTOR signaling and resulting in some of the structural and functional alterations observed in the aging myocardium [ 67 , 69 , 70 , 71 , 72 ]. On the other hand, the altered substrates in the TCA cycle in the present study have not been reported in other metabolomic profiling analyses related to aging.…”

Section: Discussionsupporting

confidence: 64%

Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy

Díaz

Burgess

Burchmore

et al. 2022

IJMS

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Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy.

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Section: Discussionsupporting

confidence: 64%

Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy

Díaz

Burgess

Burchmore

et al. 2022

IJMS

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“…As BCAA are essential amino acids and must be obtained from dietary sources, this signature suggests that increasing BCAA catabolism and thus reducing BCAA levels may signal that the body is fasting. Interestingly, recent studies have suggested that BCAA may contribute to cardiac and skeletal myocyte hypertrophy in a circadian manner [ 46 , 47 ]. In these studies, consumption of high BCAAs at the beginning or the end of the awake period led to differing effects on myocyte hypertrophy [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

BDK inhibition acts as a catabolic switch to mimic fasting and improve metabolism in mice

Bollinger¹,

Peloquin²,

Libera³

et al. 2022

Molecular Metabolism

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“…Another recent study found that doubling dietary BCAAs promoted hyperphagia, obesity, and early mortality (Solon‐Biet et al, 2019 ). A time‐of‐day feeding study also identified that feeding BCAA‐enriched meals at the end of wake periods in mice resulted in enhanced cardiovascular growth and detrimental remodeling in a circadian clock‐dependent manner (Latimer et al, 2021 ). These studies differ in means and degree of supplementation, which may explain some of these seemingly contradictory results.…”

Section: Dietary Intake Of Bcaas Affects Health and Longevitymentioning

confidence: 99%

Protein restriction and branched‐chain amino acid restriction promote geroprotective shifts in metabolism

2022

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Around the globe, human life expectancy increased by almost 20 years between 1950 (Collaborators, 2018. Despite the effect of the global COVID-19 pandemic, which has caused life expectancy in the United States to slightly decline (Arias et al., 2021), advances in medicine have shifted population demographics, and humans older than 65 now represent the fastest growing age group worldwide (United Nations, 2019). As a result, the portion of deaths attributed to noncommunicable diseases, such as age-related diseases, has risen and will continue to rise (Foreman et al., 2018).Though human life expectancy has largely increased, the prevalence of obesity and related disorders has grown rapidly, threatening the quality and duration of healthy years for an ever-expanding aged population. Obesity is more than tripled in men and doubled in women from 1975 to 2014, and 43% of American adults aged 40-59 are now obese (Collaboration, 2016). Obesity is increasingly impacting younger individuals, with about 40% of children now overweight

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Branched chain amino acids selectively promote cardiac growth at the end of the awake period

Cited by 34 publications

References 48 publications

Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy

Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy

BDK inhibition acts as a catabolic switch to mimic fasting and improve metabolism in mice

Protein restriction and branched‐chain amino acid restriction promote geroprotective shifts in metabolism

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