Untargeted metabolomics analysis of ischemia–reperfusion-injured hearts ex vivo from sedentary and exercise-trained rats

Parry, Traci L.; Starnes, Joseph W.; O’Neal, Sara; Bain, James R.; Muehlbauer, Michael J.; Honcoop, Aubree; Ilaiwy, Amro; Christopher, Peter; Patterson, Cam; Willis, Monte S.

doi:10.1007/s11306-017-1303-y

Cited by 21 publications

(19 citation statements)

References 54 publications

(55 reference statements)

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“…Finally, some affected metabolites are involved in multiple metabolic pathways making the biochemical interpretation more complex. A more mechanistic understanding of the observed metabolic changes would have been better evaluated through a flux balance analysis using 13 C or 15 N tracers; however, the nature of the investigated exercise regime in duration and animal numbers is financially prohibited.…”

Section: Discussionmentioning

confidence: 99%

“…Since rodents share similar molecular mechanisms in disease pathogenesis and present metabolic homogeneity with humans, the relationship between short-term, − chronic (1–6 months), − and single bout exercise to several pathophysiological factors such as obesity, , T2DM, ,, hypertension, heart physiology, , and aging has been investigated using animal models. The effect of lifelong exercise in relation to aging on female , and male , rats has been the focus of our research activities in recent years.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

et al. 2022

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Regular physical exercise has been investigated as a primary preventive measure of several chronic diseases and premature death. Moreover, it has been shown to synchronize responses across multiple organs. In particular, hepatic tissue has proven to be a descriptive matrix to monitor the effect of physical activity. In this study, we performed an untargeted metabolomics-based analysis of hepatic tissue extracts from rats that have undergone either lifelong or chronic exercise training. For this purpose, 56 hepatic samples were collected and were analyzed by UHPLC-TOF-MS in negative ionization mode. This approach involved untargeted metabolite detection on hepatic tissue extracts accompanied by an inhouse retention time/accurate mass library enabling confident metabolite identification. Unsupervised (PCA) and supervised (OPLS-DA) multivariate analysis showed significant metabolic perturbation on a panel of 28 metabolites, including amino acids, vitamins, nucleotides, and sugars. The training regime employed in this study resulted in a probable acceleration of the bioenergetic processes (glycolysis, glycogen metabolism), promoted catabolism of purines, and supplied biosynthetic precursors via the pentose phosphate pathway and pentose and glucuronate interconversions. Overall, the applied methodology was able to discriminate the different training schedules based on the rat liver metabolome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

et al. 2022

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“…Mounting evidence has suggested that exercise may improve cardiovascular function through indirect actions on lipid and insulin profiles [11,43]. In addition, non-target GC-MS metabolomics analysis of rat hearts revealed that endurance training offered cardioprotection against ischemia-reperfusion injury possibly through modulating protein quality control, CoA biosynthesis and ammonia recycling [44]. Taken together, greater emphasis should be geared towards metabolic adaptations and mechanisms underlying metabolic flexibility, such as autophagy, during and after exercise.…”

Section: Contemporary Theory Behind Exercise-induced Cardiovasculamentioning

confidence: 99%

Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health

Tian

Chen

et al. 2019

Cells

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Physical exercise promotes cardiorespiratory fitness, and is considered the mainstream of non-pharmacological therapies along with lifestyle modification for various chronic diseases, in particular cardiovascular diseases. Physical exercise may positively affect various cardiovascular risk factors including body weight, blood pressure, insulin sensitivity, lipid and glucose metabolism, heart function, endothelial function, and body fat composition. With the ever-rising prevalence of obesity and other types of metabolic diseases, as well as sedentary lifestyle, regular exercise of moderate intensity has been indicated to benefit cardiovascular health and reduce overall disease mortality. Exercise offers a wide cadre of favorable responses in the cardiovascular system such as improved dynamics of the cardiovascular system, reduced prevalence of coronary heart diseases and cardiomyopathies, enhanced cardiac reserve capacity, and autonomic regulation. Ample clinical and experimental evidence has indicated an emerging role for autophagy, a conservative catabolism process to degrade and recycle cellular organelles and nutrients, in exercise training-offered cardiovascular benefits. Regular physical exercise as a unique form of physiological stress is capable of triggering adaptation while autophagy in particular selective autophagy seems to be permissive to such cardiovascular adaptation. Here in this mini-review, we will summarize the role for autophagy in particular mitochondrial selective autophagy namely mitophagy in the benefit versus risk of physical exercise on cardiovascular function.

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“…Recent technological advances in this field has allowed the discovery of new biomarkers of diseases such as coronary artery disease, septic shock and brain tumors as well as the discovery of new drugs 1-5 . Metabolomic analysis has also deepened our understanding of several disease models, leading to the discovery of new pathways or targets for drug therapies that could later be applied to the treatment of various diseases [6][7][8][9][10][11] . Indeed, metabolomics are closer to the phenotype of a given disease compared with transcriptomic or proteomic analysis, both of which are prone to downstream modifications and changes in activities 1,12 .Several techniques, tools and software platforms exist to study metabolomics, all of which complement each other 13 .…”

mentioning

confidence: 99%

Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach

Rashad

Saigusa

Yamazaki

et al. 2020

Sci Rep

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Understanding the root causes of neuronal vulnerability to ischemia is paramount to the development of new therapies for stroke. Transient global cerebral ischemia (tGCI) leads to selective neuronal cell death in the CA1 sub-region of the hippocampus, while the neighboring CA3 sub-region is left largely intact. By studying factors pertaining to such selective vulnerability, we can develop therapies to enhance outcome after stroke. Using untargeted liquid chromatography-mass spectrometry, we analyzed temporal metabolomic changes in CA1 and CA3 hippocampal areas following tGCI in rats till the setting of neuronal apoptosis. 64 compounds in CA1 and 74 in CA3 were found to be enriched and statistically significant following tGCI. Pathway analysis showed that pyrimidine and purine metabolism pathways amongst several others to be enriched after tGCI in CA1 and CA3. Metabolomics analysis was able to capture very early changes following ischemia. We detected 6 metabolites to be upregulated and 6 to be downregulated 1 hour after tGCI in CA1 versus CA3. Several metabolites related to apoptosis and inflammation were differentially expressed in both regions after tGCI. We offer a new insight into the process of neuronal apoptosis, guided by metabolomic profiling that was not performed to such an extent previously.Metabolomics is the study of metabolite composition of cells, tissues or biological fluids. Recent technological advances in this field has allowed the discovery of new biomarkers of diseases such as coronary artery disease, septic shock and brain tumors as well as the discovery of new drugs 1-5 . Metabolomic analysis has also deepened our understanding of several disease models, leading to the discovery of new pathways or targets for drug therapies that could later be applied to the treatment of various diseases [6][7][8][9][10][11] . Indeed, metabolomics are closer to the phenotype of a given disease compared with transcriptomic or proteomic analysis, both of which are prone to downstream modifications and changes in activities 1,12 .Several techniques, tools and software platforms exist to study metabolomics, all of which complement each other 13 . The application of these tools has greatly enhanced our understanding of the pathophysiology of diseases in almost every field of research 14 . In the field of neuroscience, metabolomic analysis is used to study stroke 15 , brain tumors 16 , traumatic brain injury (TBI) 17,18 , neurodegenerative diseases 19 , hypoxic-ischemic encephalopathy 20 and depression 21 to name a few 22 . The application of metabolomic tools to study brain diseases have greatly enhanced our understanding of different pathologies, for example; we demonstrated the upregulation of the ceramide "Cer(d18:0/18:0)" and phosphocreatine following transient ischemia-reperfusion in mice using a mass spectrometric imaging approach 15 . Several studies have highlighted an array of small molecules, amino acids and lipids that were linked to stroke severity, progression or post-stroke cognitive deficits [23][...

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Untargeted metabolomics analysis of ischemia–reperfusion-injured hearts ex vivo from sedentary and exercise-trained rats

Cited by 21 publications

References 54 publications

Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health

Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach

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