达格列净通过FGFR1-LKB1-AMPK信号通路促进白色脂肪组织的棕色化。
Dapagliflozin promotes browning of white adipose tissue through the FGFR1-LKB1-AMPK signaling pathway.
作者信息
Lv Yue, Zhao Chengrui, Jiang Qiuyan, Rong Yilin, Ma Mingfeng, Liang Lili, Li Weiping, Zhang Jiuxuan, Xu Ning, Wu Huiwen
机构信息
Science and Technology Center of Fenyang College, Shanxi Medical University, No. 16 Xueyuan Road, Fenyang, Shanxi, 032200, People's Republic of China.
Cultivation Key Laboratory of Metabolic Cardiovascular Diseases Research, Fenyang, 032200, People's Republic of China.
出版信息
Mol Biol Rep. 2024 Apr 21;51(1):562. doi: 10.1007/s11033-024-09540-3.
BACKGROUND
Obesity is associated with a wide variety of metabolic disorders that impose significant burdens on patients and society. The "browning" phenomenon in white adipose tissue (WAT) has emerged as a promising therapeutic strategy to combat metabolic disturbances. However, though the anti-diabetic drug dapagliflozin (DAPA) is thought to promote "browning," the specific mechanism of this was previously unclear.
METHODS
In this study, C57BL/6 J male mice were used to establish an obesity model by high-fat diet feeding, and 3T3-L1 cells were used to induce mature adipocytes and to explore the role and mechanism of DAPA in "browning" through a combination of in vitro and in vivo experiments.
RESULTS
The results show that DAPA promotes WAT "browning" and improves metabolic disorders. Furthermore, we discovered that DAPA activated "browning" through the fibroblast growth factor receptors 1-liver kinase B1-adenosine monophosphate-activated protein kinase signaling pathway.
CONCLUSION
These findings provide a rational basis for the use of DAPA in treating obesity by promoting the browning of white adipose tissue.
背景
肥胖与多种代谢紊乱相关，给患者和社会带来了沉重负担。白色脂肪组织（WAT）中的“褐变”现象已成为对抗代谢紊乱的一种有前景的治疗策略。然而，尽管抗糖尿病药物达格列净（DAPA）被认为可促进“褐变”，但其具体机制此前尚不清楚。
方法
在本研究中，使用C57BL/6 J雄性小鼠通过高脂饮食建立肥胖模型，并使用3T3-L1细胞诱导成熟脂肪细胞，通过体外和体内实验相结合的方式探讨DAPA在“褐变”中的作用及机制。
结果
结果表明，DAPA促进WAT“褐变”并改善代谢紊乱。此外，我们发现DAPA通过成纤维细胞生长因子受体1-肝激酶B1-腺苷单磷酸激活的蛋白激酶信号通路激活“褐变”。
结论
这些发现为使用DAPA通过促进白色脂肪组织褐变来治疗肥胖提供了合理依据。
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