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Background Erythritol is both a common nonnutritive sweetener and an endogenous product of glucose metabolism. Recent reports suggest that elevated plasma erythritol is a predictive biomarker of cardiometabolic disease onset and complications. Objectives Although short-term erythritol consumption has been evaluated, the effect of chronically elevated circulating erythritol on adiposity and glucose metabolism has not. This study investigated the effect of longer-term erythritol consumption on weight gain and glucose tolerance in young/adolescent mice. Methods Four erythritol supplementation experiments were completed and analyzed separately in male C57BL/6J mice. In experiments 1 and 2, mice aged 8 wk or 20 wk, respectively, were randomly allocated to consume 16% fat diet (LFD) or LFD with 40 g/kg erythritol. In experiments 3 and 4, mice aged 8 wk or 20 wk were fed 45% fat diet (HFD) or HFD with 40 g/kg erythritol (HFD + ERY). In each experiment, we compared the effect of erythritol consumption on plasma erythritol, body weight and composition, glucose tolerance, and brown adipose tissue (BAT) uncoupling protein 1 (UCP1) expression. We also investigated relative endogenous tissue erythritol concentrations in a subset of control (LFD or HFD) mice in experiments 1 and 3. Results There was no effect of erythritol supplementation on body weight or glucose tolerance in experiments 1–3. In experiment 4, in the 20-wk-old mice fed HFD or HFD + ERY, there was a significant interaction of time and erythritol on body weight (P < 0.0001), but the main effect of diet was not significant. Plasma erythritol was elevated 40-fold in mice consuming erythritol-supplemented diets relative to mice consuming LFD or HFD controls. We found no effect of chronic erythritol consumption on BAT UCP1 protein concentrations. Liver and kidney tissue contained significantly higher endogenous erythritol than quadriceps and visceral adipose (P < 0.001) in young mice fed LFD and HFD. Conclusions In young/adolescent mice, prolonged erythritol consumption did not significantly affect body weight, composition, or glucose tolerance.

BackgroundErythritol is a predictive biomarker of cardiometabolic diseases and is produced from glucose metabolism through the pentose phosphate pathway (PPP). Little is known regarding the regulation of endogenous erythritol synthesis in humans.ObjectiveIn the present study, we investigated the stimuli that promote erythritol synthesis in human lung carcinoma cells and characterized potential points of regulation along the PPP.MethodsHuman A549 lung carcinoma cells were chosen for their known ability to synthesize erythritol. A549 cells were treated with potential substrates for erythritol production, including glucose, fructose, and glycerol. Using siRNA knockdown, we assessed the necessity of enzymes G6PD, TKT, TALDO, and SORD for erythritol synthesis. We also used position-specific 13C-glucose tracers to determine whether the carbons for erythritol synthesis are derived directly from glycolysis or through the oxidative PPP. Finally, we assessed if erythritol synthesis responds to oxidative stress using chemical and genetic models.ResultsIntracellular erythritol was directly associated with media glucose concentration. In addition, siRNA knockdown of TKT or SORD inhibited erythritol synthesis, whereas siG6PD did not. Both chemically induced oxidative stress and constitutive activation of the antioxidant response transcription factor NRF2 elevated intracellular erythritol.ConclusionOur findings indicate that in A549 cells, erythritol synthesis is proportional to flux through the PPP and is regulated by non-oxidative PPP enzymes.

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