Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats

Dotzert, Michelle; Murray, Michael; McDonald, Matthew W.; Olver, T. Dylan; Velenosi, Thomas J.; Hennop, Anzel; Noble, Earl G.; Urquhart, Brad L.; Melling, C.W. James

doi:10.1038/srep26379

Cited by 25 publications

(18 citation statements)

References 62 publications

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“…However, this assumption is merely speculative since we do not assess plasma insulin levels. In contrast to our results regarding glucose levels, exercise training after STZ did not prevent hyperglycemia, but increased skeletal muscle fatty acid oxidation and decreased intramyocellular lipid accumulation, which is associated with lower insulin resistance [Dotzert et al, ].…”

Section: Discussioncontrasting

confidence: 99%

Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle

Carvalho

Silva

Serafini

et al. 2016

J of Cellular Biochemistry

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Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H O production was not different between groups. Addition of ADP to the medium did not decrease H O production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O consumption, and exercise prevented this reduction. The H O production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 118: 678-685, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussioncontrasting

confidence: 99%

Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle

Carvalho

Silva

Serafini

et al. 2016

J of Cellular Biochemistry

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“…For metabolomics analysis, plasma samples were thawed at 4 °C and proteins were precipitated using a 3:1 ratio of ice-cold acetonitrile to sample as previously described 28,29 . The acetonitrile contained α-aminopimelic acid (100 μM, Toronto Research Chemicals) and chlorpropamide (2.5 μM, Sigma) as internal standards for HILIC and RPLC, respectively.…”

Section: Methodsmentioning

confidence: 99%

Untargeted metabolomics reveals N, N, N-trimethyl-L-alanyl-L-proline betaine (TMAP) as a novel biomarker of kidney function

Velenosi

Thomson

Tonial

et al. 2019

Sci Rep

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The diagnosis and prognosis of chronic kidney disease (CKD) currently relies on very few circulating small molecules, which can vary by factors unrelated to kidney function. In end-stage renal disease (ESRD), these same small molecules are used to determine dialysis dose and dialytic clearance. Therefore, we aimed to identify novel plasma biomarkers to estimate kidney function in CKD and dialytic clearance in ESRD. Untargeted metabolomics was performed on plasma samples from patients with a single kidney, non-dialysis CKD, ESRD and healthy controls. For ESRD patients, pre- and post-dialysis plasma samples were obtained from several dialysis modalities. Metabolomics analysis revealed over 400 significantly different features in non-dialysis CKD and ESRD plasma compared to controls while less than 35 features were significantly altered in patients with a single kidney. N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP, AUROC = 0.815) and pyrocatechol sulfate (AUROC = 0.888) outperformed creatinine (AUROC = 0.745) in accurately identifying patients with a single kidney. Several metabolites accurately predicted ESRD; however, when comparing pre-and post-hemodialysis, TMAP was the most robust biomarker of dialytic clearance for all modalities (AUROC = 0.993). This study describes TMAP as a novel potential biomarker of kidney function and dialytic clearance across several hemodialysis modalities.

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“…The physiological [17] and metabolic [18] alterations derived from training are well-established and there are several studies which investigated these through a metabolic profiling approach. In both humans [19,20,21,22,23,24] and rodents [25,26,27,28,29,30,31,32,33,34], metabolomics-based studies decipher changes in amino acids, carbohydrates’ metabolism, Krebs cycle and lipids’ metabolism and other intermediates of biochemical pathways featured as energy providers. These findings on altered metabolism derived from exercise on humans were recently reviewed [35].…”

Section: Introductionmentioning

confidence: 99%

“…These findings on altered metabolism derived from exercise on humans were recently reviewed [35]. For the metabolomics study of exercise in rodent models, GC–MS (Gas Chromatography–Mass Spectrometry) [25,26,27], UPLC–MS/MS (Ultra Performance Liquid Chromatography–tandem Mass Spectrometry) [32,33] and NMR spectroscopy [28,29,30,31,34] have been used to analyze blood [26,28,30], urine [31], and tissue extracts [25,27,29,32,33], mainly from skeletal muscles and hepatic tissue. Recently, a study has provided evidence that rat exercise response imitates human’s response, in blood samples [36].…”

Section: Introductionmentioning

confidence: 99%

Impact of Exercise and Aging on Rat Urine and Blood Metabolome. An LC-MS Based Metabolomics Longitudinal Study

et al. 2017

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Aging is an inevitable condition leading to health deterioration and death. Regular physical exercise can moderate the metabolic phenotype changes of aging. However, only a small number of metabolomics-based studies provide data on the effect of exercise along with aging. Here, urine and whole blood samples from Wistar rats were analyzed in a longitudinal study to explore metabolic alterations due to exercise and aging. The study comprised three different programs of exercises, including a life-long protocol which started at the age of 5 months and ended at the age of 21 months. An acute exercise session was also evaluated. Urine and whole blood samples were collected at different time points and were analyzed by LC-MS/MS (Liquid Chromatography–tandem Mass Spectrometry). Based on their metabolic profiles, samples from trained and sedentary rats were differentiated. The impact on the metabolome was found to depend on the length of exercise period with acute exercise also showing significant changes. Metabolic alterations due to aging were equally pronounced in sedentary and trained rats in both urine and blood analyzed samples.

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Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats

Cited by 25 publications

References 62 publications

Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle

Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle

Untargeted metabolomics reveals N, N, N-trimethyl-L-alanyl-L-proline betaine (TMAP) as a novel biomarker of kidney function

Impact of Exercise and Aging on Rat Urine and Blood Metabolome. An LC-MS Based Metabolomics Longitudinal Study

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