Dapagliflozin promotes browning of white adipose tissue through the FGFR1-LKB1-AMPK signaling pathway

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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. Conclusion: These findings provide a rational basis for the use of DAPA in treating obesity by promoting the browning of white adipose tissue.
Funding Information
  • This study was supported by the Key Research and Development Project for Introducing High-level Scientific and Technological Talents in Lvliang City (grant number 2022RC29)
  • Cultivation Key laboratory of Metabolic Cardiovascular Diseases Research (grant number TSGJ001)

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