关键词: 赤藓糖醇, 代谢组学, 血糖, 鞘脂代谢, 三羧酸循环, 核黄素代谢

Abstract:

Objective To discuss the effect of erythritol on glucose and lipid metabolism in the body， and to clarify the mechanism of erythritol affecting liver metabolism based on metabonomics. Methods The male ICR mice were randomly divided into normal group， sucrose group （2% sucrose）， low dose of erythritol （1% erythritol） group， medium dose of erythritol （2% erythritol） group， and high dose of erythritol （4% erythritol） group， with 10 mice in each group. The corresponding concentrations of sucrose and erythritol solutions were prepared and placed in water bottles， and the mice were allowed to drink and eat freely for 12 consecutive weeks； the body mass， food intakes， and water intakes of the mice in various groups were measured. Commercial kits were used to detect the serum triglyceride （TG）， total cholesterol （TC）， and blood glucose levels of the mice in various groups； the liver indexes of the mice were calculated. Ultra performance liquid chromatography-orbitrap exactive mass spectrometry （UPLC-OE-MS） non-targeted metabonomics was used to detect the liver metabolites of the mice normal group and high dose of erythritol group； bioinformatics analysis was used to screen the differential liver metabolites between the two groups with variable importance in projection （VIP）>1 and adjusted P<0.05； Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed to investigate the functional roles of the differential liver metabolites. Results ?Compared with normal group， there were no significant differences in the body mass， food intake， liver index， and blood lipid levels of the mice in various groups （P>0.05）； compared with normal group， the blood glucose level of the mice in high dose of erythritol group was significantly increased （P<0.01）. The metabonomics analysis of the liver tissues of the mice in two groups identified 1 144 metabolites， mainly including lipids and lipid-like molecules （17.39%）， organic acids and derivatives （10.87%）， organic heterocyclic compounds （5.80%）， and organic oxygen compounds （5.07%）. Compared with normal group， there were 138 differential liver metabolites in the mice in high dose of erythritol group， among which 112 metabolites were up-regulated and 26 metabolites were down-regulated. The KEGG signal pathway enrichment analysis results showed that the differential metabolites were mainly enriched in metabolism， steroid hormone biosynthesis， cortisol synthesis and metabolism， and Cushing’s syndrome pathways； the further topological analysis of the metabolic pathways results showed that the differential metabolites were mainly involved in sphingolipid metabolism， tricarboxylic acid cycle， riboflavin metabolism， steroid hormone biosynthesis， and purine metabolism signal pathways. Conclusion Long-term intake of high dose of erythritol can increase the blood glucose level in the mice， and the mechanism may be that it affects the tricarboxylic acid cycle by interfering with riboflavin metabolism and interferes with sphingolipid metabolism， leading to impairment of the blood glucose control system.

Key words: Erythritol, Metabonomics, Blood glucose, Sphingolipid metabolism, Tricarboxylic acid cycle, Riboflavin metabolism