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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: | FEDER-02/SAICT/2017/028147 LA/P/0058/2020 REEQ/481/QUI/2006 info:eu-repo/grantAgreement/UIDP/04539/2020 RECI/QEQQFI/0168/2012 PD/BD/135178/2017 UIDB/04539/2020 info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/NEU/04539/2013/PT PINFRA/22125/2016 |
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. | URI: | https://hdl.handle.net/10316/114156 | ISSN: | 0952-3480 1099-1492 |
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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