Metabolomics atlas of oral 13C-glucose tolerance test in mice

Lopes, Magno A.; Brejchová, Kristýna; Riecan, Martin; Nováková, Michaela; Rossmeisl, Martin; Čajka, Tomáš; Kuda, Ondřej

doi:10.1016/j.celrep.2021.109833

Cited by 26 publications

(17 citation statements)

References 42 publications

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“…The first hypothesis is that the influx into the muscle glycolytic system does not increase as much as the blood glucose levels. A recent study showed that the influx of orally administered labelled glucose into the glycolysis of gastrocnemius muscle (white muscle), which was used in this study, is much smaller than that of soleus muscle (red muscle) 28 . The second hypothesis is that the efflux of glycolysis increased by activation as much as the influx.…”

Section: Discussionmentioning

confidence: 96%

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

Kokaji

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Hatano

et al. 2022

Sci Rep

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Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity.

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Section: Discussionmentioning

confidence: 96%

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

Kokaji

Eto

Hatano

et al. 2022

Sci Rep

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“…Using this same technology, we also illustrate that glucose uptake and oxidation is reduced in a model of DIO, which accurately reflects an IR phenotype. Overall, the utility of stable isotopes is becoming prevalent for metabolic fate mapping ( Buescher et al, 2015 ; Jang et al, 2018 ; Lopes et al, 2021 ; Diehl et al, 2022 ; Pachnis et al, 2022 ) and clinical diagnostics ( Modak, 2007 ; Braden, 2009 ), and we demonstrate that use of 13 C-glucose faithfully recapitulates metabolic deregulation in models of lung tumor progression and DIO.…”

Section: Introductionmentioning

confidence: 69%

Exogenous detection of 13C-glucose metabolism in tumor and diet-induced obesity models

et al. 2022

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Metabolic rewiring is a hallmark feature prevalent in cancer cells as well as insulin resistance (IR) associated with diet-induced obesity (DIO). For instance, tumor metabolism shifts towards an enhanced glycolytic state even under aerobic conditions. In contrast, DIO triggers lipid-induced IR by impairing insulin signaling and reducing insulin-stimulated glucose uptake. Based on physiological differences in systemic metabolism, we used a breath analysis approach to discriminate between different pathological states using glucose oxidation as a readout. We assessed glucose utilization in lung cancer-induced cachexia and DIO mouse models using a U-13C glucose tracer and stable isotope sensors integrated into an indirect calorimetry system. Our data showed increased 13CO2 expired by tumor-bearing (TB) mice and a reduction in exhaled 13CO2 in the DIO model. Taken together, our findings illustrate high glucose uptake and consumption in TB animals and decreased glucose uptake and oxidation in obese mice with an IR phenotype. Our work has important translational implications for the utility of stable isotopes in breath-based detection of glucose homeostasis in models of lung cancer progression and DIO.

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“…Only the CATEGORY and CLASS levels are labeled to optimize space use and prevent overlapping labels. The Cytoscape network was built to visualize the quantitative data and statistics …”

Section: Methodsmentioning

confidence: 99%

LORA, Lipid Over-Representation Analysis Based on Structural Information

et al. 2023

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With the increasing number of lipidomic studies, there is a need for an efficient and automated analysis of lipidomic data. One of the challenges faced by most existing approaches to lipidomic data analysis is lipid nomenclature. The systematic nomenclature of lipids contains all available information about the molecule, including its hierarchical representation, which can be used for statistical evaluation. The Lipid Over-Representation Analysis (LORA) web application () analyzes this information using the Java-based Goslin framework, which translates lipid names into a standardized nomenclature. Goslin provides the level of lipid hierarchy, including information on headgroups, acyl chains, and their modifications, up to the “complete structure” level. LORA allows the user to upload the experimental query and reference data sets, select a grammar for lipid name normalization, and then process the data. The user can then interactively explore the results and perform lipid over-representation analysis based on selected criteria. The results are graphically visualized according to the lipidome hierarchy. The lipids present in the most over-represented terms (lipids with the highest number of enriched shared structural features) are defined as Very Important Lipids (VILs). For example, the main result of a demo data set is the information that the query is significantly enriched with “glycerophospholipids” containing “acyl 20:4” at the “sn-2 position”. These terms define a set of VILs (e.g., PC 18:2/20:4;O and PE 16:0/20:4(5,8,10,14);OH). All results, graphs, and visualizations are summarized in a report. LORA is a tool focused on the smart mining of epilipidomics data sets to facilitate their interpretation at the molecular level.

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Metabolomics atlas of oral 13C-glucose tolerance test in mice

Abstract: Highlights d A systems-level organ-specific metabolomics atlas of mouse tissues d 13 C 6 -glucose tracer tissue distribution during glucose tolerance test d Interactive online application for metabolic pathway exploration d LC-MS data resource covering polar metabolites and complex lipids

Cited by 26 publications

References 42 publications

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

Exogenous detection of 13C-glucose metabolism in tumor and diet-induced obesity models

LORA, Lipid Over-Representation Analysis Based on Structural Information

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