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ObjectiveEctodysplasin A (EDA), a newly discovered hepatokine, has recently been considered to be closely related to glycolipid metabolism disorders, but the pathophysiological effects of EDA are still poorly understood. This study was the first time to determine the level of serum EDA in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and to explore the relationships between serum EDA levels and various metabolic indexes.MethodsA total of 184 subjects were enrolled in the study, including 92 subjects with newly diagnosed T2DM and 92 subjects with age- and sex-matched normal glucose tolerance (NGT). Serum EDA levels were determined using enzyme-linked immunosorbent assay (ELISA). Oral glucose tolerance test, glycosylated hemoglobin c (HbA1c), and insulin were also measured.ResultsSerum EDA levels were significantly increased in the T2DM group than in the NGT group (359.91 ± 117.99 vs. 265.82 ± 86.51 pg/ml, p < 0.001). Serum EDA levels were positively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, 2-hour postprandial plasma glucose (2hPG), fasting plasma insulin (FIns), fasting C peptide (FCP), triglyceride (TG), HOMA-IR, and negatively correlated with high-density lipoprotein cholesterol (HDL-c) and HOMA-β (p < 0.05). Multiple stepwise regression analysis demonstrated that 2hPG and FIns were independent influencing factors of serum EDA level (p < 0.05). Logistic regression analysis showed that serum EDA level was significantly independently correlated with T2DM (p < 0.05).ConclusionsSerum EDA levels are significantly higher in T2DM patients, suggesting that EDA may play a role in the occurrence and development of T2DM.

Except for improving glycemic control, liraglutide, one of the glucagon-like peptide-1 receptor agonists, has exerted promising therapeutic effects for dyslipidemia. It has been proved that gut microbiota plays a dramatic role in regulating lipid metabolism. This study aims to explore whether liraglutide could improve dyslipidemia by modulating the gut microbiota in mice fed a high-fat diet (HFD). The C57BL/6 mice were fed a HFD to establish an animal model of dyslipidemia, and then administered with liraglutide or normal saline (NS) for 12 weeks. Indices of glucolipid metabolism were evaluated. Gut microbiota of the mice was analyzed by 16S rRNA gene sequencing. Compared with HFD group, liraglutide significantly alleviated weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels, meanwhile elevating high-density lipoprotein cholesterol (HDL) levels (all p < 0.05). The gut microbiota analysis revealed that liraglutide greatly reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes, with a concomitant drop in the Firmicutes/Bacteroidetes ratio. Meanwhile, liraglutide dramatically changed the overall composition, promoted the growth of beneficial microbes (Akkermansia, Lactobacillus, Parabacteroides, Oscillospira, etc.), and inhibited the growth of harmful microbes (AF12, Shigella, Proteobacteria, Xenorhabdus, etc.). Especially, the relative abundance of Akkermansia increased the most after liraglutide treatment. Correlation analysis suggested that TC and LDL were positively correlated with some harmful bacteria, and negatively associated with beneficial bacteria. This study confirmed that liraglutide had a certain therapeutic effect on dyslipidemia in HFD-fed mice and could regulate the composition of the gut microbiota associated with lipid metabolism, especially Akkermansia. Thus, affecting gut microbiota might be a potential mechanism of liraglutide in attenuating dyslipidemia.

BACKGROUNDEtodysplasin A (EDA), a newly discovered hepatokine, has recently been considered to be closely related to glycolipid metabolism disorders, but the pathophysiological effects of EDA are still poorly understood. This study was the first time to determine the level of serum EDA in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and to explore the relationships between serum EDA levels and various metabolic indexes.METHODS A total of 184 subjects were enrolled in the study, including 92 subjects with newly diagnosed T2DM and 92 subjects with age- and sex- matched normal glucose tolerance (NGT). Serum EDA levels were determined using enzyme-linked immunosorbent assay (ELISA). And oral glucose tolerance test, glycosylated hemoglobin c(HbA1c), blood lipid and insulin were also measured. Insulin resistance (IR) and islet β-cell function were assessed by homeostasis model assessment (HOMA).RESULTSSerum EDA levels were significantly increased in the T2DM group than in the NGT group (359.91 ± 117.99 vs. 265.82 ± 86.51pg/mL, P<0.001). Serum EDA levels were positively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, 2-hour postprandial plasma glucose(2hPG), fasting plasma insulin (FIns), fasting C peptide (FCP), triglyceride (TG), HOMA-IR, and negatively correlated with high-density lipoprotein cholesterol (HDL-c) and HOMA-β (P<0.05). Multiple stepwise regression analysis demonstrated that 2hPG and FIns were independent influencing factors of serum EDA level (P<0.05). Logistic regression analysis showed that serum EDA level was significantly independent correlated with T2DM (P<0.05). CONCLUSIONS Serum EDA level are significantly higher in T2DM patients, indicating that circulating EDA may be involved in the pathogenesis of T2DM.