SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(7), P. 443 - 462

Published: Jan. 6, 2023

Language: Английский

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Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1211 - 1211

Published: Jan. 19, 2024

This comprehensive review explores the critical role of fatty acid (FA) metabolism in cardiac diseases, particularly heart failure (HF), and implications for therapeutic strategies. The heart’s reliance on ATP, primarily sourced from mitochondrial oxidative metabolism, underscores significance metabolic flexibility, with oxidation (FAO) being a dominant source. In HF, shifts occur an altered FA uptake FAO, impacting function contributing to disease progression. Conditions like obesity diabetes also lead disturbances, resulting cardiomyopathy marked by over-reliance dysfunction, lipotoxicity. Therapeutic approaches targeting diseases have evolved, focusing inhibiting or stimulating FAO optimize energetics. Strategies include using CPT1A inhibitors, PPARα agonists, enhancing biogenesis function. However, effectiveness varies, reflecting complexity remodeling HF. Hence, treatment strategies should be individualized, considering that energy is intricate tightly regulated. aim overall function, recognizing pivotal FAs need further research develop effective therapies, promising new improve

Language: Английский

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Aldose reductase inhibition alleviates diabetic cardiomyopathy and is associated with a decrease in myocardial fatty acid oxidation

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 28, 2023

Abstract Background Cardiovascular diseases, including diabetic cardiomyopathy, are major causes of death in people with type 2 diabetes. Aldose reductase activity is enhanced hyperglycemic conditions, leading to altered cardiac energy metabolism and deterioration function adverse remodeling. Because disturbances can promote inefficiency, we hypothesized that aldose inhibition may mitigate cardiomyopathy via normalization metabolism. Methods Male C57BL/6J mice (8-week-old) were subjected experimental diabetes/diabetic (high-fat diet [60% kcal from lard] for 10 weeks a single intraperitoneal injection streptozotocin (75 mg/kg) at 4 weeks), following which animals randomized treatment either vehicle or AT-001, next-generation inhibitor (40 mg/kg/day) 3 weeks. At study completion, hearts perfused the isolated working mode assess Results by AT-001 improved diastolic efficiency This attenuation was associated decreased myocardial fatty acid oxidation rates (1.15 ± 0.19 vs 0.5 0.1 µmol min −1 g dry wt presence insulin) but no change glucose compared control group. In addition, fibrosis hypertrophy also mitigated cardiomyopathy. Conclusions Inhibiting ameliorates dysfunction diabetes, be due decline oxidation, indicating novel approach alleviate patients

Language: Английский

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Double-side role of short chain fatty acids on host health via the gut-organ axes

Animal nutrition, Journal Year: 2024, Volume and Issue: 18, P. 322 - 339

Published: May 17, 2024

Short chain fatty acids (SCFA) exist in dietary foods and are produced by the fermentation of gut microbiota, considered an important element for regulating host health. Through blood circulation, SCFA obtained from have impact on intestinal health as well vital organs host. It has been recognized that is "vital organ" As microbial metabolites, could create "axis" connecting to other organs. Therefore, "gut-organ axes" become a focus research recent years analyze organism In this review, we summarized sources, absorption properties, function both peripheral tissues (brain, kidney, liver, lung, bone cardiovascular) way axes". exert beneficial pathological role various ways, which effects more pronounced. addition, reflected preventive therapeutic effects. More importantly, mechanisms behinds provided insight into SCFA, assisting development novel strategies maintaining

Language: Английский

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Short-Chain Fatty Acids in Gut–Heart Axis: Their Role in the Pathology of Heart Failure

Journal of Personalized Medicine, Journal Year: 2022, Volume and Issue: 12(11), P. 1805 - 1805

Published: Nov. 1, 2022

Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Accumulating evidence has implicated the possible contribution of gut microbiota-derived metabolites, short-chain fatty acids (SCFAs), on pathology variety diseases. The changes SCFA concentration were reported be observed in various cardiovascular diseases including HF experimental animals humans. causes hypoperfusion and/or congestion gut, which may lead lowered production SCFAs, possibly through pathological microenvironment microbiota composition. Recent studies suggest that SCFAs play significant role HF, an agonistic effect G-protein-coupled receptors, histone deacetylases (HDACs) inhibition, restoration mitochondrial function, amelioration cardiac inflammatory response, utilization as energy source, remote attributable protective other organs. Collectively, might key mediator gut–heart axis. However, these mechanisms have not been entirely clarified need further investigation.

Language: Английский

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The Anti-Inflammatory and Antioxidant Impact of Dietary Fatty Acids in Cardiovascular Protection in Older Adults May Be Related to Vitamin C Intake

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 267 - 267

Published: Jan. 25, 2023

Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), docosahexaenoic (DHA), α-linolenic (ALA), or linoleic (LA), have a particular role in counteracting cardiovascular diseases. They may regulate antioxidant potential and inflammatory reactions. Little is known whether other saturated acids (e.g., short-chain (SCFA) butyric caproic acid) monounsaturated be involved the level of Vitamin C intake affect these processes. The purpose this study was to assess impact on plasma salivary total capacity (TAC), inflammation marker C-reactive protein (CRP). Eighty older adults (60-79 years old) were divided into two groups with high (n = 39) low 41) intake. In group SCFA, ALA, LA positively correlated TAC indices, intake, decreased subjects higher SCFA Salivary CRP negatively corresponded EPA, DHA whole (p < 0.05 for all). Fatty influence CRP.

Language: Английский

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Gut Failure: A Review of the Pathophysiology and Therapeutic Potentials in the Gut–Heart Axis

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(7), P. 2567 - 2567

Published: March 29, 2023

Despite considerable advances in the field, heart failure (HF) still poses a significant disease burden among affected individuals since it continues to cause high morbidity and mortality rates. Inflammation is considered play key role progression, but exact underlying pathophysiological mechanisms involved have not yet been fully elucidated. The gut, as potential source of inflammation, could feasibly explain state low-grade inflammation seen patients with chronic HF. Several derangements composition microbiota population, coupled an imbalance between favorable harmful metabolites followed by gut barrier disruption eventually bacterial translocation, contribute cardiac dysfunction aggravate On other hand, HF-associated congestion hypoperfusion alters intestinal function, thereby creating vicious cycle. Based on this evidence, novel pharmaceutical agents developed their therapeutic use has tested both animal human subjects. ultimate goal these efforts reverse aforementioned block cascade. This review summarizes gut-related causative pathways implicated HF pathophysiology, well associated interventions described literature.

Language: Английский

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Recent Advances in Microbiota-Associated Metabolites in Heart Failure

Biomedicines, Journal Year: 2023, Volume and Issue: 11(8), P. 2313 - 2313

Published: Aug. 21, 2023

Heart failure is a risk factor for adverse events such as sudden cardiac arrest, liver and kidney death. The gut microbiota its metabolites are directly linked to the pathogenesis of heart failure. As emerging studies have increased in literature on role specific development, this review highlights summarizes current evidence underlying mechanisms associated with We found that microbiota-derived short chain fatty acids, bile branched-chain amino tryptophan indole derivatives well trimethylamine-derived metabolite, trimethylamine N-oxide, play critical roles promoting through various mechanisms. Mainly, they modulate complex signaling pathways nuclear kappa-light-chain-enhancer activated B cells, Bcl-2 interacting protein 3, NLR Family Pyrin Domain Containing inflammasome, Protein kinase RNA-like endoplasmic reticulum kinase. also highlighted beneficial other cardiovascular metabolic diseases.

Language: Английский

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Gut-derived short-chain fatty acids bridge cardiac and systemic metabolism and immunity in heart failure

The Journal of Nutritional Biochemistry, Journal Year: 2023, Volume and Issue: 120, P. 109370 - 109370

Published: May 26, 2023

Language: Английский

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2-[18F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity

Molecular Imaging and Biology, Journal Year: 2025, Volume and Issue: 27(1), P. 109 - 119

Published: Jan. 14, 2025

Treatment of pediatric cancers with doxorubicin is a common and predictable cause cardiomyopathy. Early diagnosis treatment-induced cardiotoxicity intervention are major determinants for the prevention advanced disease. The onset cardiomyopathies often accompanied by profound changes in lipid metabolism, including an enhanced uptake short-chain fatty acids (SCFA). Therefore, we explored utility 2-[18F]fluoropropionic acid ([18F]FPA), SCFA analog, as imaging biomarker cardiac injury mice exposed to doxorubicin. Cardiotoxicity dysfunction were induced 8-dose regimen (cumulative dose 24 mg/kg) administered over 14 days. effects exposure assessed measurement heart weights, left ventricular ejection fractions, blood troponin levels. Whole body [18F]FPA uptakes determined PET tissue gamma counting presence or absence AZD3965, pharmacological inhibitor monocarboxylate transporter 1 (MCT1). Radiation absorbed doses estimated using time-activity concentrations. Significantly higher was observed doxorubicin-treated animals. This remained constant from 30 120 min post-injection. Pharmacological inhibition MCT1-mediated transport AZD3965 selectively decreased tissues other than heart. Co-administration contrast diseased while reducing overall radioactivity. [18F]FPA, especially when co-administered new tool metabolism occurring response doxorubicin-induced cardiomyopathy PET.

Language: Английский

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