Physiological impact of in vivo stable isotope tracing on cancer metabolism

The gut microbiota influences host epigenetics by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-CoA, a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.

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Stable Isotope Tracing Metabolomics to Investigate the Metabolic Activity of Bioactive Compounds for Cancer Prevention and Treatment

Cancers ◽

10.3390/cancers12082147 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2147

Author(s):

Feroza K. Choudhury ◽

G. Lavender Hackman ◽

Alessia Lodi ◽

Stefano Tiziani

Keyword(s):

Stable Isotope ◽

Cancer Prevention ◽

Cancer Cells ◽

Bioactive Compounds ◽

Molecular Mechanisms ◽

Cancer Metabolism ◽

Metabolic Reprogramming ◽

Isotope Tracing ◽

Production And Consumption ◽

Relative Production

A major hallmark of cancer is the metabolic reprogramming of cancer cells to fuel tumor growth and proliferation. Various plant-derived bioactive compounds efficiently target the metabolic vulnerabilities of cancer cells and exhibit potential as emerging therapeutic agents. Due to their safety and common use as dietary components, they are also ideal for cancer prevention. However, to render their use as efficient as possible, the mechanism of action of these phytochemicals needs to be well characterized. Stable isotope tracing is an essential technology to study the molecular mechanisms by which nutraceuticals modulate and target cancer metabolism. The use of positionally labeled tracers as exogenous nutrients and the monitoring of their downstream metabolites labeling patterns enable the analysis of the specific metabolic pathway activity, via the relative production and consumption of the labeled metabolites. Although stable isotope tracing metabolomics is a powerful tool to investigate the molecular activity of bioactive compounds as well as to design synergistic nutraceutical combinations, this methodology is still underutilized. This review aims to investigate the research efforts and potentials surrounding the use of stable isotope tracing metabolomics to examine the metabolic alterations mediated by bioactive compounds in cancer.

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Unveiling Cancer Metabolism through Spontaneous and Coherent Raman Spectroscopy and Stable Isotope Probing

Cancers ◽

10.3390/cancers13071718 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1718

Author(s):

Jiabao Xu ◽

Tong Yu ◽

Christos E. Zois ◽

Ji-Xin Cheng ◽

Yuguo Tang ◽

...

Keyword(s):

Raman Spectroscopy ◽

Stable Isotope ◽

Cancer Metabolism ◽

Stable Isotope Probing ◽

Metabolic Reprogramming ◽

Label Free ◽

Future Directions ◽

Biochemical Processes ◽

Coherent Raman

Metabolic reprogramming is a common hallmark in cancer. The high complexity and heterogeneity in cancer render it challenging for scientists to study cancer metabolism. Despite the recent advances in single-cell metabolomics based on mass spectrometry, the analysis of metabolites is still a destructive process, thus limiting in vivo investigations. Being label-free and nonperturbative, Raman spectroscopy offers intrinsic information for elucidating active biochemical processes at subcellular level. This review summarizes recent applications of Raman-based techniques, including spontaneous Raman spectroscopy and imaging, coherent Raman imaging, and Raman-stable isotope probing, in contribution to the molecular understanding of the complex biological processes in the disease. In addition, this review discusses possible future directions of Raman-based technologies in cancer research.

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An In Vivo Rat α-D-glucose Stable Isotope Homeostasis Drug Discovery Screen: A Targeted Metabolomics Approach

Current Topics in Medicinal Chemistry ◽

10.2174/1568026617666170707130401 ◽

2017 ◽

Vol 17 (24) ◽

Author(s):

Gary W. Caldwell ◽

Wensheng Lang

Keyword(s):

Drug Discovery ◽

Stable Isotope ◽

Targeted Metabolomics

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Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

Proceedings of The Nutrition Society ◽

10.1017/s0029665120008034 ◽

2021 ◽

pp. 1-9

Author(s):

Jorn Trommelen ◽

Andrew M. Holwerda ◽

Philippe J. M. Pinckaers ◽

Luc J. C. van Loon

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Stable Isotope ◽

Dietary Protein ◽

Protein Metabolism ◽

Muscle Protein ◽

Human Subjects ◽

Whole Body ◽

Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

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