Circulating metabolic signatures of heart failure in precision cardiology

Abstract

Precision cardiology aims to implement personalized health care and precise medical decisions based on the specific characteristics of individuals. Metabolic remodeling plays a causal role in the pathogenesis of heart failure (HF). Changes in metabolic pathways such as substrate preference, high-energy phosphate metabolism and amino acid metabolism, are involved in pathological structural remodeling and functional impairment. These metabolic alterations are usually not restricted in the cardiac tissue, but also manifest in circulation. In clinical practice, blood sample is routinely used for HF screening. Metabolomics is an emerging omics technology that provides an efficient way to acquire dynamic metabolic profiles in circulation. An increasing number of metabolic biomarkers have been implicated in disease progression, making it possible to fight HF in a more effective and precise way. This review summarizes the modern analytical techniques in metabolomics as well as emerging circulating metabolites during the pathogenesis of HF, aiming to provide new insights into the prevention, diagnosis and treatment of HF in the era of precision medicine.

Progress in The Research of Lactate Metabolism Disruption And Astrocyte‐Neuron Lactate Shuttle Impairment in Schizophrenia: A Comprehensive Review

“…[62] However, glycolysis was significantly reduced and mitochondrial enzyme activity was impaired only in FCX. In contrast to the results of the previous study, Xie J et al found that glycolysis and lactylation were increased in the hippocampus of SCZ mice induced by MK-801 (0.4 mg kg −1 d −1 , 13d), and that an inhibitor of glycolysis (2-DG) ameliorated the behavioral abnormalities in SCZ mice [63] In addition, subcutaneous injection of MK-801 (0.2 mg kg −1 d −1 , 4d) in neonatal male Wistar rats transiently blocked the medial prefrontal cortex (mPFC) region of NMDA receptors that can lead to disturbances in energy metabolism and inhibited the rise in lactate levels caused by plantar stress, [64] which did not have a significant effect on adult rats. However, in another study, it was found that, given the same dose of MK-801, extracellular lactate concentration (eLAC) in the mPFC of adult male Wistar rats was elevated above the baseline level (≈65 μ L −1 ) and that MK-801 prolonged the transient elevation of eLAC induced by foot stress.…”

“…Abnormalities in lactate metabolism are prevalent in the brain [43,[55][56][57][58][59] and blood [19,21,60,61] of patients with schizophrenia, as well as in the brains of animal models of SCZ. [43,[62][63][64][65][66][67][68][69][70][71] Currently, in addition to the determination of blood lactate levels in schizophrenic patients by GC × GC-TOFMS-based small-polarity metabolite analysis platforms, [60] CE-TOFMS and LC-TOFMS, [61] fully automated blood gas analyzers, [21] stoichiometrically related nuclear magnetic resonance (NMR) analyses, [19] and highperformance liquid chromatography (HPLC), [72] magnetic resonance spectroscopy (MRS) [56,58,59] and 7-Tesla MRI [57] have been increasingly used for the detection of brain lactate levels in patients with SCZ. Most studies of animal models of SCZ have examined their brain lactate, with commonly used assays including 13C and 1H MRS, [62,66] 11.7 T MRS, [67] microdialysis, [65] R fu, [70] and lactate kits.…”

Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets

“…[79,80] Increased FA dependency in diabetic cardiomyopathy Disturbances in lipid metabolism are detected during the early stages of diabetes and cardiac diseases. [81,82] Circulating levels of FAs increase in both T1DM and T2DM [83,84] because of impaired insulin action in the lipolysis of adipose tissues and the liver. [85,86] In addition, the increase in circulating FAs suppresses glucose uptake and oxidation.…”

Comprehensive Metabolomic Analysis of Human Heart Tissue Enabled by Parallel Metabolite Extraction and High-Resolution Mass Spectrometry

“…The heart contracts incessantly to supply oxygenated blood to the entire body and thus, requires a constant source of energy to fuel its high energy demands . The heart is a “metabolic omnivore” that utilizes a variety of fuel substrates, ranging from very polar (e.g., amino acid and nucleosides) to very nonpolar (e.g., lipids). − Therefore, a comprehensive metabolomic analysis is critical to understanding cardiac metabolism; however, it remains challenging as the broad range of metabolite polarities makes extraction and detection difficult. − …”