关键词: AMPK Dapagliflozin FGFR1 LKB1 Obesity White adipose tissue browning

Mesh : Animals Male Mice 3T3-L1 Cells Adipocytes / metabolism drug effects Adipose Tissue, Brown / drug effects metabolism Adipose Tissue, White / metabolism drug effects AMP-Activated Protein Kinases / metabolism Benzhydryl Compounds / pharmacology Diet, High-Fat Glucosides / pharmacology Mice, Inbred C57BL Obesity / metabolism drug therapy Protein Serine-Threonine Kinases / metabolism Receptor, Fibroblast Growth Factor, Type 1 / metabolism genetics Signal Transduction / drug effects

来  源:   DOI:10.1007/s11033-024-09540-3   PDF(Pubmed)

Abstract:
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.
CONCLUSIONS: These findings provide a rational basis for the use of DAPA in treating obesity by promoting the browning of white adipose tissue.
摘要:
背景:肥胖与给患者和社会带来巨大负担的多种代谢紊乱有关。白色脂肪组织(WAT)中的“褐变”现象已成为对抗代谢紊乱的有希望的治疗策略。然而,尽管抗糖尿病药物达格列净(DAPA)被认为可以促进“褐变”,“这种具体机制以前还不清楚。
方法:在本研究中,用C57BL/6J雄性小鼠通过高脂饮食建立肥胖模型,和3T3-L1细胞用于诱导成熟脂肪细胞,并通过体内外实验结合探讨DAPA在“褐变”中的作用和机制。
结果:结果表明,DAPA促进了WAT\“褐变\”并改善了代谢紊乱。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-磷酸腺苷活化蛋白激酶信号通路激活“褐变”。
结论:这些发现为DAPA通过促进白色脂肪组织褐变治疗肥胖提供了合理的依据。
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