دورية أكاديمية
Enrichment of hepatic glycogen and plasma glucose from H₂18 O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice
| العنوان: | Enrichment of hepatic glycogen and plasma glucose from H₂18 O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice |
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| المؤلفون: | 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. |
| بيانات النشر: | Wiley-Blackwell |
| سنة النشر: | 2023 |
| المجموعة: | Universidade de Coimbra: Estudo Geral |
| مصطلحات موضوعية: | fructose, gluconeogenesis, glycogenesis, isotope shift, triose phosphates, Mice, Animals, Glucose, Water, Liver, Glycerol, Trioses, Phosphates, Blood Glucose, Liver Glycogen |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0952-3480 1099-1492 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; 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.; https://hdl.handle.net/10316/114156Test |
| DOI: | 10.1002/nbm.4837 |
| الإتاحة: | https://doi.org/10.1002/nbm.4837Test https://hdl.handle.net/10316/114156Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2554C416 |
| قاعدة البيانات: | BASE |
| تدمد: | 09523480 10991492 |
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| DOI: | 10.1002/nbm.4837 |