The effects of liraglutide in mice with diet-induced obesity studied by metabolomics
The effects of liraglutide in mice with diet-induced obesity studied by metabolomics
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DOI：
10.1530/joe-16-0478
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发表时间：
2017-04-01
影响因子：
4
通讯作者：
Haluzik, Martin
中科院分区：
文献类型：
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作者：
Buganova, Martina;Pelantova, Helena;Haluzik, Martin
利拉鲁肽是胰高血糖素样肽-1受体激动剂，广泛用于治疗2型糖尿病。最近，它已被证明可以降低2型糖尿病和高心血管风险患者的心血管发病率和死亡率。尽管利拉鲁肽的主要作用方式众所周知，但尚未研究其在代谢水平的详细作用。为此，我们使用核磁共振光谱法探索了利拉鲁肽治疗2周对患有13周高脂饮食诱导的肥胖和糖尿病的C57 BL/6雄性小鼠的影响，以捕获治疗引起的尿液代谢谱变化。利拉鲁肽给药降低了体重和脂肪垫重量沿着血糖和甘油三酯水平。与高脂肪饲料喂养对照组相比，NMR光谱法鉴别出11种代谢产物受利拉鲁肽给药显著影响。这些代谢物包括参与烟酰胺腺嘌呤二核苷酸代谢、脂肪酸β-氧化和微生物组变化的代谢物。尽管利拉鲁肽给药后发生变化的大多数代谢物与先前在相似小鼠模型中给予维格鲁肽后发现的代谢物相似，但肌酐、牛磺酸和胡芦巴碱的变化对利拉鲁肽给药具有特异性。这些变化的意义及其在人类抗糖尿病治疗个性化中的可能用途需要进一步研究。
Liraglutide is the glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes mellitus. Recently, it has been demonstrated to decrease cardiovascular morbidity and mortality in patients with type 2 diabetes and high cardiovascular risk. Although the major modes of liraglutide action are well-known, its detailed action at the metabolic level has not been studied. To this end, we explored the effect of 2-week liraglutide treatment in C57BL/6 male mice with obesity and diabetes induced by 13 weeks of high-fat diet using NMR spectroscopy to capture the changes in urine metabolic profile induced by the therapy. The liraglutide treatment decreased body and fat pads weight along with blood glucose and triglyceride levels. NMR spectroscopy identified 11 metabolites significantly affected by liraglutide treatment as compared to high-fat diet-fed control group. These metabolites included ones involved in nicotinamide adenine dinucleotide metabolism, beta-oxidation of fatty acids and microbiome changes. Although majority of the metabolites changed after liraglutide treatment were similar as the ones previously identified after vildagliptin administration in a similar mouse model, the changes in creatinine, taurine and trigonelline were specific for liraglutide administration. The significance of these changes and its possible use in the personalization of antidiabetic therapy in humans requires further research.