PT  - JOURNAL ARTICLE
AU  - Semira R. Ortiz
AU  - Martha S. Field
TI  - Elevated plasma and urinary erythritol is a biomarker of excess simple carbohydrate intake in mice
AID  - 10.1101/2022.12.04.519026
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.12.04.519026
4099  - http://biorxiv.org/content/early/2022/12/04/2022.12.04.519026.short
4100  - http://biorxiv.org/content/early/2022/12/04/2022.12.04.519026.full
AB  - Background Elevated serum erythritol is a predictive biomarker of diabetes and cardiovascular incidence and complications. Erythritol is synthesized endogenously from glucose, but little is known regarding the origin of elevated circulating erythritol in vivo.Objective In vitro evidence indicates that intracellular erythritol is elevated by high-glucose cell culture conditions and that final step of erythritol synthesis is catalyzed by the enzymes SORD and ADH1. The purpose of this study was to determine if dietary intake and/or diet-induced obesity (DIO) affect erythritol synthesis in mice, and if this relationship is modified by loss of the enzymes SORD or ADH1.Methods First, 8-week-old, male Sord+/+, Sord-/-, Adh1+/+, and Adh1-/- mice were fed either low-fat diet (LFD) with 10% fat-derived calories or DIO high-fat diet (HFD) with 60% fat-derived calories for 8 weeks. Plasma and tissue erythritol were measured using GC-MS. Second, wild-type 8-week-old C57BL/6J mice were fed LFD or HFD with plain drinking water or 30% sucrose water for 8 weeks. Blood glucose and plasma and urinary erythritol were measured in non-fasted and fasted samples. Tissue erythritol was measured following sacrifice. Finally, Sord+/+ and Sord-/- mice were fed LFD with 30% sucrose water for two weeks, then non-fasted plasma, urine, and tissue erythritol were quantified.Results Plasma and tissue erythritol were not impacted by loss of Sord or Adh1 on LFD or HFD. In wild-type mice, consumption of 30% sucrose water significantly elevated plasma and urinary erythritol on both LFD and HFD compared to plain water. Sord genotype did not affect plasma or urinary erythritol in response to sucrose feeding, but Sord-/- mice had reduced kidney erythritol content compared to wildtype littermates in response to sucrose.Conclusions Sucrose intake, not high-fat diet, elevates erythritol synthesis and excretion in mice. Loss of ADH1 or SORD does not significantly impact erythritol levels in mice.Competing Interest StatementThe authors have declared no competing interest.ADH1alcohol dehydrogenase 1DIOdiet-induced obesityG6PDglucose-6-phosphate dehydrogenaseHFDhigh-fat dietIPGTTintraperitoneal glucose tolerance testKOknockoutLFDlow-fat dietPPPpentose phosphate pathwaySORDsorbitol dehydrogenaseTKTtransketolaseWTwildtype.