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Global Stable-isotope Tracing Metabolomics Reveals System-wide Metabolic Alternations in Aging Drosophila

ABSTRACT:

System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Yet, delineating system-wide metabolic homeostasis at the whole-organism level remains non-trivial. Here, we develop a global isotope tracing metabolomics technology to measure labeled metabolites with a metabolome-wide coverage. Using Drosophila as an aging model organism, we probe the in vivo tracing kinetics with quantitative information on labeling patterns, extents and rates on a metabolome-wide scale. We curate a system-wide metabolic network to characterize metabolic homeostasis and disclose a system-wide loss of metabolic coordinations that impacts both intra- and inter-tissue metabolic homeostasis significantly during Drosophila aging. Importantly, we reveal an unappreciated metabolic diversion from glycolysis to serine metabolism and purine metabolism as Drosophila aging. The developed technology facilitates a system-level understanding of metabolic regulation in living organisms.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - negative - hilic

SUBMITTER: Masslab Zhu

PROVIDER: MTBLS3322 | MetaboLights | 2022-06-16

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS3322	Other
	FILES	Other
	a_MTBLS3322_293T_NEG_LC-MS_hilic_metabolite_profiling.txt	Txt
	a_MTBLS3322_293T_POS_LC-MS_hilic_metabolite_profiling.txt	Txt
	a_MTBLS3322_Head_NEG_LC-MS_hilic_metabolite_profiling.txt	Txt

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Global Stable-isotope Tracing Metabolomics Reveals System-wide Metabolic Alternations in Aging Drosophila

Project description:System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Yet, delineating system-wide metabolic homeostasis at the whole-organism level remains non-trivial. Here, we develop a global isotope tracing metabolomics technology to measure labeled metabolites with a metabolome-wide coverage. Using Drosophila as an aging model organism, we probe the in vivo tracing kinetics with quantitative information on labeling patterns, extents and rates on a metabolome-wide scale. We curate a system-wide metabolic network to characterize metabolic homeostasis and disclose a system-wide loss of metabolic coordinations that impacts both intra- and inter-tissue metabolic homeostasis significantly during Drosophila aging. Importantly, we reveal an unappreciated metabolic diversion from glycolysis to serine metabolism and purine metabolism as Drosophila aging. The developed technology facilitates a system-level understanding of metabolic regulation in living organisms.

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