Combined treatment with teneligliptin and canagliflozin additively suppresses high-fat diet-induced body weight gain in mice with modulation of lipid metabolism-related gene expression
Combined treatment with teneligliptin and canagliflozin additively suppresses high-fat diet-induced body weight gain in mice with modulation of lipid metabolism-related gene expression
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特力利汀和卡格列净联合治疗可通过调节脂质代谢相关基因表达来额外抑制高脂饮食引起的小鼠体重增加
DOI：
10.1016/j.ejphar.2023.175682
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发表时间：
2023
影响因子：
5
通讯作者：
Goto Tsuyoshi
中科院分区：
文献类型：
--
作者：
Kawarasaki Satoko;Sawazaki Honami;Iijima Hiroaki;Takahashi Haruya;Nomura Wataru;Inoue Kazuo;Kawada Teruo;Goto Tsuyoshi
在2型糖尿病（T2DM）的治疗中，综合管理多种危险因素，如血糖、体重和血脂，对于预防疾病进展非常重要。虽然临床上经常使用二肽基肽酶-4 （DPP-4）抑制剂与钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂联用，但除了葡萄糖代谢外，这种联用的影响尚未得到深入的研究。在这项研究中，我们评估了DPP-4抑制剂teneligliptin和SGLT2抑制剂canagliflozin联合治疗对高脂饮食（HFD）诱导的肥胖小鼠体重和脂质代谢的影响。我们发现，替尼格列汀或卡格列净单药治疗对高脂肪饮食引起的体重增加和减少腹股沟白色脂肪组织（iWAT）质量有抑制作用，联合治疗可减少体重增加和iWAT质量。Teneligliptin显著增加了光照期的耗氧量，这种效果在联合治疗中保持不变。联合处理没有改变脂肪组织中产热相关基因的mRNA表达水平，但有累加诱导棕色脂肪组织中脂肪酸氧化相关基因mRNA表达的趋势，有累加降低iWAT和肝组织中脂肪酸合成相关基因mRNA表达的趋势。这些结果表明，tenigliptin和canaglilozin联合治疗可以通过增加氧气消耗和调节脂质代谢相关基因的表达来抑制hfd诱导的体重增加。这种联合治疗可能为T2DM和肥胖患者提供有效的体重管理。
In the treatment of type 2 diabetes mellitus (T2DM), comprehensive management of multiple risk factors, such as blood glucose, body weight, and lipids, is important to prevent disease progression. Although the combination of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor is often used clinically, the effects of this combination, other than glucose metabolism, have yet to be thoroughly investigated. In this study, we evaluated the effects of combined treatment with a DPP-4 inhibitor, teneligliptin, and an SGLT2 inhibitor, canagliflozin, on the body weight and lipid metabolism in high-fat diet (HFD)-induced obese mice. We found that monotherapy with teneligliptin or canagliflozin showed suppressive effects on high-fat diet-induced body weight gain and reduced inguinal white adipose tissue (iWAT) mass, and combined treatment additively reduced body weight gain and iWAT mass. Teneligliptin significantly increased oxygen consumption during the light phase, and this effect was preserved in the combined treatment. The combined treatment did not alter the mRNA expression levels of thermogenesis-related genes in adipose tissue but showed the tendency to additively induce mRNA of fatty acid oxidation-related genes in brown adipose tissue and tended to additively decrease mRNA of fatty acid synthesis-related genes in iWAT and liver tissues. These results suggest that combined treatment with teneligliptin and canagliflozin additively suppresses HFD-induced body weight gain with increasing oxygen consumption and modulating the expression of lipid metabolism-related genes. This combination therapy may provide effective body weight management for patients with T2DM and obesity.