Chronic phosphodiesterase type 5 inhibition has beneficial effects on subcutaneous adipose tissue plasticity in type 2 diabetic mice

J Cell Physiol. 2018 Nov;233(11):8411-8417. doi: 10.1002/jcp.26796. Epub 2018 May 24.

Abstract

Different adipose tissue (AT) depots are associated with multiple metabolic risks. Phosphodiesterase type 5 (PDE5) is involved in adipocyte physiology and PDE5 inhibition may affect adipogenesis and ameliorate white AT quality. The aim of this study is to investigate the distribution of AT and the composition of the stroma-vascular fraction (SVF) of subcutaneous AT (SAT) in type 2 diabetic mice after prolonged treatment with a PDE5 inhibitor, Sildenafil. 18 db/db mice were treated with Sildenafil or vehicle for 12 weeks. AT distribution was monitored and SAT was processed for isolation of SVF by flow cytometry. Sildenafil induced an overall reduction in AT, mainly in visceral AT (VAT), compared with SAT. In Sildenafil-treated mice, the mean change in body weight from baseline positively correlated with VAT, but not with SAT. Characterization of SVF of SAT showed an increase in the frequency of M2 macrophages and endothelial cells in treated mice. Sildenafil improved the maintenance of SAT homeostasis and distribution.

Keywords: adipocyte progenitors; endothelial cells; macrophages; phosphodiesterase type 5; sildenafil; subcutaneous adipose tissue; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipogenesis / drug effects
  • Animals
  • Cell Plasticity / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / genetics*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Disease Models, Animal
  • Humans
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / pathology
  • Mice
  • Obesity / drug therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Phosphodiesterase 5 Inhibitors / administration & dosage*
  • Sildenafil Citrate / administration & dosage*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism
  • Subcutaneous Fat / pathology

Substances

  • Phosphodiesterase 5 Inhibitors
  • Sildenafil Citrate
  • Cyclic Nucleotide Phosphodiesterases, Type 5