Sucrose Intake Elevates Erythritol in Plasma and Urine in Male Mice

Abstract

Background: Elevated serum erythritol concentration 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.

Objectives: 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 sorbitol dehydrogenase (SORD) and alcohol dehydrogenase (ADH) 1. The purpose of this study was to determine whether dietary intake and/or diet-induced obesity affect erythritol synthesis in mice and whether this relationship is modified by the loss of the enzymes SORD or ADH1.

Methods: First, 8-wk-old male Sord^+/+, Sord^-/-, Adh1^+/+, and Adh1^-/- mice were fed either low-fat diet (LFD) with 10% fat-derived calories or diet-induced obesity high-fat diet (HFD) with 60% fat-derived calories for 8 wk. Plasma and tissue erythritol concentrations were measured using gas chromatography-mass spectrometry. Second, male wild-type 8-wk-old C57BL/6J mice were fed LFD or HFD with plain drinking water or 30% sucrose water for 8 wk. Blood glucose and plasma and urinary erythritol concentrations were measured in nonfasted and fasted samples. Tissue erythritol was measured after killing. Finally, male Sord^+/+ and Sord^-/- mice were fed LFD with 30% sucrose water for 2 wk; then, nonfasted plasma, urine, and tissue erythritol concentrations were quantified.

Results: Plasma and tissue erythritol concentrations were not affected by loss of Sord or Adh1 in mice fed LFD or HFD. In wild-type mice, consumption of 30% sucrose water significantly elevated plasma and urinary erythritol concentrations on both LFD-fed and HFD-fed mice compared with that of plain water. Sord genotype did not affect plasma or urinary erythritol concentration in response to sucrose feeding, but Sord^-/- mice had reduced kidney erythritol content compared with wild-type littermates in response to sucrose.

Conclusions: Sucrose intake, not HFD, elevates erythritol synthesis and excretion in mice. Loss of ADH1 or SORD does not significantly affect erythritol concentration in mice.

Keywords: alcohol dehydrogenase; erythritol; glucose; obesity; pentose phosphate pathway; sorbitol dehydrogenase; sucrose.