Dipeptidyl peptidase IV (DPP-IV) inhibition prevents fibrosis in adipose tissue of obese mice

Ana Patrícia Marques, Janete Cunha-Santos, Helena Leal, Lígia Sousa-Ferreira, Luís Pereira de Almeida, Cláudia Cavadas, Joana Rosmaninho-Salgado*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background During the development of obesity the expansion of white adipose tissue (WAT) leads to a dysregulation and an excessive remodeling of extracellular matrix (ECM), leading to fibrosis formation. These ECM changes have high impact on WAT physiology and may change obesity progression. Blocking WAT fibrosis may have beneficial effects on the efficacy of diet regimen or therapeutical approaches in obesity. Since dipeptidyl peptidase IV (DPP-IV) inhibitors prevent fibrosis in tissues, such as heart, liver and kidney, the objective of this study was to assess whether vildagliptin, a DPP-IV inhibitor, prevents fibrosis in WAT in a mouse model of obesity, and to investigate the mechanisms underlying this effect. Methods We evaluated the inhibitory effect of vildagliptin on fibrosis markers on WAT of high-fat diet (HFD)-induced obese mice and on 3T3-L1 cell line of mouse adipocytes treated with a fibrosis inducer, transforming growth factor beta 1 (TGFβ1). Results Vildagliptin prevents the increase of fibrosis markers in WAT of HFD-fed mice and reduces blood glucose, serum triglycerides, total cholesterol and leptin levels. In the in vitro study, the inhibition of DPP-IV with vildagliptin, neuropeptide Y (NPY) treatment and NPY Y1 receptor activation prevents ECM deposition and fibrosis markers increase induced by TGFβ1 treatment. Conclusions Vildagliptin prevents fibrosis formation in adipose tissue in obese mice, at least partially through NPY and NPY Y1 receptor activation. General significance This study highlights the importance of vildagliptin in the treatment of fibrosis that occur in obesity.
Original languageEnglish
Pages (from-to)403-413
Number of pages11
JournalBiochimica et Biophysica Acta - General Subjects
Volume1862
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

Keywords

  • Dipeptidyl peptidase IV inhibitor
  • Extracellular matrix
  • Fibrosis
  • Neuropeptide Y
  • Obesity
  • Vildagliptin

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