Ketone Ester Treatment Increases Cardiac Ketone Utilization and Reduces Cardiac Inflammation in a Porcine Model of Acute Myocardial Infarction

Yurista, Salva; Welsh, Aidan; Jiang, William; Eder, R.; Chen, Shi; Bonner, Benjamin; Foster, A. E.; Coll‐Font, Jaume; Rosenzweig, Anthony; Nguyen, Christopher

doi:10.1016/s0735-1097(22)02030-7

Cited by 3 publications

(2 citation statements)

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“…These results may suggest the activation of adaptive and functional changes in fatty acid liver metabolism in the early phase of CHF, resulting in increased production of ketone bodies. Ketone bodies display not only liver protective effects 59 but also pronounced cardioprotective effects, 60 thus excessive ketone release in postprandial phase might represent an important mechanism by which liver regulates cardiac metabolism. Of note, downregulation of ACAT1 together with changes in other proteins related to lipid metabolism in isolated hepatocytes in 12‐month‐old Tgαq*44 mice indicated a downregulation of fatty acid synthesis.…”

Section: Discussionmentioning

confidence: 99%

Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice

Wojnar‐Lason,

Tyrankiewicz,

Kij

et al. 2024

Acta Physiologica

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AimChronic heart failure (CHF) is often linked to liver malfunction and systemic endothelial dysfunction. However, whether cardio‐hepatic interactions in heart failure involve dysfunction of liver sinusoidal endothelial cells (LSECs) is not known. Here we characterize LSECs phenotype in early and end stages of chronic heart failure in a murine model.MethodsRight ventricle (RV) function, features of congestive hepatopathy, and the phenotype of primary LSECs were characterized in Tgαq*44 mice, with cardiomyocyte‐specific overexpression of the Gαq protein, at the age of 4‐ and 12‐month representative for early and end‐stage phases of CHF, respectively.Results4‐ and 12‐month‐old Tgαq*44 mice displayed progressive impairment of RV function and alterations in hepatic blood flow velocity resulting in hepatic congestion with elevated GGT and bilirubin plasma levels and decreased albumin concentration without gross liver pathology. LSECs isolated from 4‐ and 12‐month‐old Tgαq*44 mice displayed significant loss of fenestrae with impaired functional response to cytochalasin B, significant changes in proteome related to cytoskeleton remodeling, and altered vasoprotective function. However, LSECs barrier function and bioenergetics were largely preserved. In 4‐ and 12‐month‐old Tgαq*44 mice, LSECs defenestration was associated with prolonged postprandial hypertriglyceridemia and in 12‐month‐old Tgαq*44 mice with proteomic changes of hepatocytes indicative of altered lipid metabolism.ConclusionTgαq*44 mice displayed right‐sided HF and altered hepatic blood flow leading to LSECs dysfunction involving defenestration, shift in eicosanoid profile, and proteomic changes. LSECs dysfunction appears as an early and persistent event in CHF, preceding congestive hepatopathy and contributing to alterations in lipoprotein transport and CHF pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice

Wojnar‐Lason,

Tyrankiewicz,

Kij

et al. 2024

Acta Physiologica

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“…Consistent with metabolism-independent effects of ketones, preclinical models of myocardial infarction and HF demonstrate that elevated levels of ketones in the circulation can improve resting cardiac function and cardiac remodeling (eg, hypertrophy, fibrosis) in both HFrEF 8 and HF with preserved ejection fraction, 10 and higher levels of ketones through KE treatment can also improve exercise tolerance in HF with preserved ejection fraction. 10 Moreover, ketone signaling can protect the heart by enhancing oxidative stress defense 11,12 and favorably affecting pathways such as autophagy and apoptosis, 12,13 further supporting the notion that elevating circulating ketone levels may provide benefit in HF through mechanisms beyond improving myocardial metabolism.…”

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confidence: 89%

Unlocking Pathways That Improve Cardiac Function in Chronic Heart Failure: Are Ketones the Key?

Sarma,

Dyck

2024

Circulation

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Fueling the Heart: What Are the Optimal Dietary Strategies in Heart Failure?

Ataran,

Pompian,

Hajirezaei

et al. 2024

Nutrients

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Objectives: Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF. Methods: In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression. Results: Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e., with ketones) and dietary strategies that impact ketogenesis. Conclusion: This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies in preventing progression and improving outcomes in the context of HF.

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Ketone Ester Treatment Increases Cardiac Ketone Utilization and Reduces Cardiac Inflammation in a Porcine Model of Acute Myocardial Infarction

Cited by 3 publications

References 0 publications

Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice

Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice

Unlocking Pathways That Improve Cardiac Function in Chronic Heart Failure: Are Ketones the Key?

Fueling the Heart: What Are the Optimal Dietary Strategies in Heart Failure?

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