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利拉鲁肽通过激活AMPK和抑制Akt来降低db/db小鼠内脏脂肪中的脂肪生成信号。

Liraglutide reduces lipogenetic signals in visceral adipose of db/db mice with AMPK activation and Akt suppression.

作者信息

Shao Yimin, Yuan Geheng, Zhang Junqing, Guo Xiaohui

机构信息

Department of Endocrinology, Peking University First Hospital, Beijing, People's Republic of China.

出版信息

Drug Des Devel Ther. 2015 Feb 18;9:1177-84. doi: 10.2147/DDDT.S79175. eCollection 2015.

Abstract

Liraglutide, a glucagon-like peptide-1 analog, has been proved to reduce body weight and visceral adipose tissue (VAT) in human studies. In this study, we aimed at examining lipogenetic signal changes in VAT after weight-loss with liraglutide in db/db mice. The mice were divided into two groups: liraglutide-treated group (n=14, 8-week-old, fasting glucose. >10 mmol/L, liraglutide 300 μg/kg twice a day for 4 weeks) and control group (n=14, saline). We found body weight gain and food intake were reduced after liraglutide treatment (P<0.05). Compared to the control group, the VAT weights were significantly lower in the treated group (2.32±0.37 g versus 3.20±0.30 g, P<0.01) than that in control group. In VAT, compared with control group, the lipogenetic transcription factors PPARγ and C/EBPα expressions were both reduced with pAMPK and pACC increased 3.5-fold and 2.31-fold respectively, while pAkt and pP38MAPK were reduced 0.38-fold and 0.62-fold respectively (P<0.01). In conclusion, VAT was reduced after weight loss with AMPK activation and Akt suppression with liraglutide treatment, which was associated with reduction of lipogenetic process in VAT.

摘要

利拉鲁肽是一种胰高血糖素样肽-1类似物,人体研究已证明其可减轻体重和减少内脏脂肪组织(VAT)。在本研究中,我们旨在检测db/db小鼠使用利拉鲁肽减重后VAT中脂肪生成信号的变化。将小鼠分为两组:利拉鲁肽治疗组(n = 14,8周龄,空腹血糖>10 mmol/L,利拉鲁肽300 μg/kg,每日两次,共4周)和对照组(n = 14,生理盐水)。我们发现利拉鲁肽治疗后体重增加和食物摄入量减少(P<0.05)。与对照组相比,治疗组的VAT重量显著更低(2.32±0.37 g对3.20±0.30 g,P<0.01)。在VAT中,与对照组相比,脂肪生成转录因子PPARγ和C/EBPα的表达均降低,而pAMPK和pACC分别增加3.5倍和2.31倍,而pAkt和pP38MAPK分别降低0.38倍和0.62倍(P<0.01)。总之,利拉鲁肽治疗通过激活AMPK和抑制Akt实现减重后VAT减少,这与VAT中脂肪生成过程的减少有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df3/4342181/9586f35aa950/dddt-9-1177Fig1.jpg

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