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

  • Mol Biol Rep. 2024 Apr 21;51(1):562. doi: 10.1007/s11033-024-09540-3.
Yue Lv  #  1 ,  Chengrui Zhao  #  1 ,  Qiuyan Jiang  1 ,  Yilin Rong  1 ,  Mingfeng Ma  2 ,  Lili Liang  2 ,  Weiping Li  3 ,  Jiuxuan Zhang  1 ,  Ning Xu  4 ,  Huiwen Wu  5  6  7
Affiliations
  • 1. Science and Technology Center of Fenyang College, Shanxi Medical University, No. 16 Xueyuan Road, Fenyang, Shanxi, 032200, People's Republic of China.
  • 2. Cultivation Key Laboratory of Metabolic Cardiovascular Diseases Research, Fenyang, 032200, People's Republic of China.
  • 3. Basic Sciences Department of Fenyang College, Shanxi Medical University, Fenyang, 032200, People's Republic of China.
  • 4. Department of Oncology, Shanxi Province Fenyang Hospital, Fenyang, 032200, People's Republic of China.
  • 5. Science and Technology Center of Fenyang College, Shanxi Medical University, No. 16 Xueyuan Road, Fenyang, Shanxi, 032200, People's Republic of China. [email protected].
  • 6. Cultivation Key Laboratory of Metabolic Cardiovascular Diseases Research, Fenyang, 032200, People's Republic of China. [email protected].
  • 7. Department of Oncology, Shanxi Province Fenyang Hospital, Fenyang, 032200, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 38644407 DOI: 10.1007/s11033-024-09540-3
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.

Keywords
AMPK; Dapagliflozin; FGFR1; LKB1; Obesity; White adipose tissue browning.
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