Quantitative Fluxomics of Circulating Metabolites.

Animals Citric Acid Cycle Fatty Acids / metabolism Glucose / metabolism Glycerol / metabolism Lactic Acid / metabolism Mice Mice, Inbred C57BL Triglycerides / metabolism
TCA cycle circulating metabolites energy metabolism in vivo flux quantification isotope tracing ketogenic diet metabolic cycling

Journal

Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170

Informations de publication

Date de publication:
06 10 2020
Historique:
received: 04 02 2020
revised: 06 04 2020
accepted: 20 07 2020
pubmed: 14 8 2020
medline: 9 11 2021
entrez: 14 8 2020
Statut: ppublish

Résumé

Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high-carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.

Identifiants

DOI: 10.1016/j.cmet.2020.07.013 PMID: 32791100 PMC: PMC7544659
pubmed: 32791100
pii: S1550-4131(20)30371-5
doi: 10.1016/j.cmet.2020.07.013
pmc: PMC7544659
mid: NIHMS1621247
pii:
doi:

Substances chimiques

Fatty Acids 0
Triglycerides 0
Lactic Acid 33X04XA5AT
Glucose IY9XDZ35W2
Glycerol PDC6A3C0OX

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

676-688.e4

Subventions

Organisme : NIH HHS
ID : S10 OD025098
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP1 DK113643
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK117066
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211437
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK019525
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK118856
Pays : United States
Organisme : NIDDK NIH HHS
ID : K99 DK117066
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests J.D.R. is a member of the Rutgers Cancer Institute of New Jersey and of the University of Pennsylvania Diabetes Research Center; a co-founder and stockholder in VL54, Sofro, and Raze Therapeutics; and advisor and stockholder in Agios Pharmaceuticals, Kadmon Pharmaceuticals, Bantam Pharmaceuticals, Colorado Research Partners, Rafael Pharmaceuticals, and L.E.A.F. Pharmaceuticals.

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Auteurs

Sheng Hui (S)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA. Electronic address: shui@hsph.harvard.edu.

Alexis J Cowan (AJ)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Xianfeng Zeng (X)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Lifeng Yang (L)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Tara TeSlaa (T)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Xiaoxuan Li (X)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Caroline Bartman (C)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Zhaoyue Zhang (Z)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Cholsoon Jang (C)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Lin Wang (L)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Wenyun Lu (W)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.

Jennifer Rojas (J)

Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Boulevard, Philadelphia, PA 19104, USA.

Joseph Baur (J)

Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Boulevard, Philadelphia, PA 19104, USA.

Joshua D Rabinowitz (JD)

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA. Electronic address: joshr@princeton.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Cycle citrique › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Lipides › Acides gras › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Glucides › Polyols › Dérivés du glycérol › Glycérol › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Hydroxyacides › Lactates › Acide lactique › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Quantitative Fluxomics of Circulating Metabolites.
questionsmedicales.fr › Lipides › Glycérides › Triglycéride › Quantitative Fluxomics of Circulating Metabolites.