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Title: Enrichment of hepatic glycogen and plasma glucose from H₂18 O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice
Authors: Coelho, Margarida 
Mahar, Rohit
Belew, Getachew D.
Torres, Alejandra
Barosa, Cristina 
Cabral, Fernando
Viegas, Ivan 
Gastaldelli, Amalia
Mendes, Vera M. 
Manadas, Bruno 
Jones, John G. 
Merritt, Matthew E. 
Keywords: fructose; gluconeogenesis; glycogenesis; isotope shift; triose phosphates
Issue Date: Feb-2023
Publisher: Wiley-Blackwell
Project: Portuguese Foundation for Science and Technology-European Comission; Research Grant: FCT-FEDER-02/SAICT/2017/028147, UIDB/0453972020, UIDP/04539/2020, LA/P/0058/2020, POCI-01-0145-FEDER- 007440, REEQ/481/QUI/2006, RECI/QEQQFI/ 0168/2012, CENTRO-07-CT62-FEDER- 402-022125, PD/BD/135178/2017; Marie Skłodowska-Curie Grant Agreement No. 722619 (Project FOIE GRAS) and Grant Agreement No. 734719 (mtFOIE GRAS); The National Mass Spectrometry Network (RNEM); Contract: POCI-01-0145-FEDER- 402-022125 (ref.: ROTEIRO/0028/2013); National Institutes of Health; NIH, Grant Numbers: R01-DK105346, R01-DK132254, P41-GM122698, and 5U2C-DK119889; National Science Foundation Cooperative Agreement DMR-1644779. 
Serial title, monograph or event: NMR in Biomedicine
Volume: 36
Issue: 2
Abstract: Deuterated water (2 H2 O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of 2 H can distort metabolic information and mediate toxicity. 18 O-water (H2 18 O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well-defined mechanisms, but to date it has not been evaluated in any animal model. Mice were given H2 18 O during overnight feeding and 18 O-enrichments of liver glycogen, triglyceride glycerol (TG), and blood glucose were quantified by 13 C NMR and mass spectrometry (MS). Enrichment of oxygens 5 and 6 relative to body water informed indirect pathway contributions from the Krebs cycle and triose phosphate sources. Compared with mice fed normal chow (NC), mice whose NC was supplemented with a fructose/glucose mix (i.e., a high sugar [HS] diet) had significantly higher indirect pathway contributions from triose phosphate sources, consistent with fructose glycogenesis. Blood glucose and liver TG 18 O-enrichments were quantified by MS. Blood glucose 18 O-enrichment was significantly higher for HS versus NC mice and was consistent with gluconeogenic fructose metabolism. TG 18 O-enrichment was extensive for both NC and HS mice, indicating a high turnover of liver triglyceride, independent of diet. Thus H2 18 O informs hepatic carbohydrate biosynthesis in similar detail to 2 H2 O but without KIE-associated risks.
ISSN: 0952-3480
DOI: 10.1002/nbm.4837
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
I&D CFE - Artigos em Revistas Internacionais
FCTUC Química - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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