Shao Yimin, Yuan Geheng, Zhang Junqing, Guo Xiaohui
Department of Endocrinology, Peking University First Hospital, Beijing, People's Republic of China.
Drug Des Devel Ther. 2015 Feb 18;9:1177-84. doi: 10.2147/DDDT.S79175. eCollection 2015.
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.
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。