Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway.
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway.
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DOI：
10.4093/dmj.2020.0187
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发表时间：
2021-11
影响因子：
5.9
通讯作者：
Cha BS
中科院分区：
文献类型：
--
作者：
Lee JY;Lee M;Lee JY;Bae J;Shin E;Lee YH;Lee BW;Kang ES;Cha BS
钠-葡萄糖共转运体2(SGLT2)抑制剂是一类具有多种降糖作用的新型抗糖尿病药物。然而，关于SGLT2抑制对能量消耗和产热的影响，有相互矛盾的结果。因此，我们研究了选择性SGLT2抑制剂伊帕格列齐对能量代谢的影响。将6周龄雄性129S6/Sv小鼠随机分为3组：正常饲料对照组、60%高脂饲料对照组和60%高脂饲料依普拉格列津治疗组。饮食和药物治疗持续16周。喂食HFD的小鼠变得肥胖，出现肝脏脂肪变性和脂肪组织肥大，但它们的随机血糖水平在正常范围内；这些特征类似于糖尿病前期条件下的代谢特征。伊帕格列齐治疗可明显减轻HFD诱导的肝脏脂肪变性，并使肥大的脂肪细胞缩小为较小的脂肪细胞。伊帕格列星治疗组内脏和皮下脂肪组织解偶联蛋白1(Ucp1)等产热相关基因表达显著上调，棕色脂肪组织脂肪酸氧化增加。这些效应与肝脏和脂肪组织中胰岛素和胰升糖素比率的显著降低以及AMP激活的蛋白激酶(AMPK)/sirtuin1(SIRT1)通路的激活有关。伊帕格列齐抑制SGLT2在129S6/Sv小鼠中显示出有益的代谢效应，这些小鼠患有模拟糖尿病前期条件的HFD诱导的肥胖。我们的数据表明，SGLT2抑制剂通过上调能量消耗，可能对糖尿病前期肥胖具有治疗潜力。
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism. Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks. The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue. SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.
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影响因子：
3.7
作者：
Chiba Y;Yamada T;Tsukita S;Takahashi K;Munakata Y;Shirai Y;Kodama S;Asai Y;Sugisawa T;Uno K;Sawada S;Imai J;Nakamura K;Katagiri H
通讯作者：
Katagiri H
影响因子：
3.7
作者：
Shimasaki T;Masaki T;Mitsutomi K;Ueno D;Gotoh K;Chiba S;Kakuma T;Yoshimatsu H
通讯作者：
Yoshimatsu H
影响因子：
5
作者：
Hayashizaki-Someya, Yuka;Kurosaki, Eiji;Takakura, Shoji
通讯作者：
Takakura, Shoji
DOI：
10.1038/nrendo.2010.187
发表时间：
2010-12
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29
作者：
Ohno H;Shinoda K;Spiegelman BM;Kajimura S
通讯作者：
Kajimura S