Lin Ke, Dong Chunyan, Zhao Binyan, Zhou Bailing, Yang Li
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
MedComm (2020). 2023 Nov 20;4(6):e416. doi: 10.1002/mco2.416. eCollection 2023 Dec.
Studies have shown that antidiabetic drugs can alter the gut microbiota. The hypoglycemic effects of the drugs can be attributed in part to certain species in the gut microbiome that help the drugs work more effectively. In addition, increasing energy expenditure via the induction of adipose tissue browning has become an appealing strategy to treat obesity and associated metabolic complications. Currently, glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment for metabolic disorders such as obesity and type 2 diabetes has been widely studied. To determine the mechanism of a long-acting GLP-1 RA affects adipose tissue browning and the gut microbiome, we treated high-fat diet mice with GLP-1 RA and demonstrated that the drug can regulate adipose tissue browning. 16S rRNA and untargeted metabolomics assays suggested that it increased the abundance of bacterium and decreased serum ceramide levels in mice. was negatively correlated with ceramide. We found that the mechanism of ceramide decline was alkaline ceramidase 2 (Acer2) overexpression. Moreover, can play a therapeutic synergistic role with GLP-1 RA, suggesting that gut microbiota can be used as a part of the treatment of diabetes.
研究表明，抗糖尿病药物可改变肠道微生物群。这些药物的降血糖作用部分可归因于肠道微生物组中的某些物种，它们有助于药物更有效地发挥作用。此外，通过诱导脂肪组织褐变来增加能量消耗已成为治疗肥胖症及相关代谢并发症的一种有吸引力的策略。目前，胰高血糖素样肽-1受体激动剂（GLP-1 RA）治疗肥胖症和2型糖尿病等代谢紊乱已得到广泛研究。为了确定长效GLP-1 RA影响脂肪组织褐变和肠道微生物群的机制，我们用GLP-1 RA治疗高脂饮食小鼠，并证明该药物可调节脂肪组织褐变。16S rRNA和非靶向代谢组学分析表明，它增加了小鼠体内细菌的丰度并降低了血清神经酰胺水平。 与神经酰胺呈负相关。我们发现神经酰胺下降的机制是碱性神经酰胺酶2（Acer2）过表达。此外， 可与GLP-1 RA发挥治疗协同作用，表明肠道微生物群可作为糖尿病治疗的一部分。
