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PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition

  • Sergio Perez-Diaz
  • Maria P. Garcia-Sobreviela
  • Yolanda Gonzalez-Irazabal
  • Beatriz Garcia-Rodriguez
  • Silvia Espina
  • Izaskun Arenaz
  • Jose M. Arbones-Mainar
Original Article
  • 58 Downloads

Abstract

Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma. We also produced a recombinant PTRF (rPTRF) and examined its impact on the functional interactions between the adipocyte and the hepatocyte in vitro. We demonstrated that PTRF can be found in human plasma, and is at least in part, carried by exosomes. In vitro treatment with rPTRF increased the hypertrophy and senescence of 3T3-L1 adipocytes. In turn, those rPTRF-treated adipocytes increased lipid accumulation in hepatocytes. Lastly, we found a positive correlation between circulating PTRF and the concentration of PTRF in the visceral fat depot. All these findings point toward the presence of an enlarged and dysfunctional visceral adipose tissue which secretes PTRF. This circulating PTRF behaves as an adipokine and may partially contribute to the well-known detrimental effects of visceral fat accumulation.

Keywords

Adipose Cavin-1 Senescence Visceral fat 

Notes

Acknowledgements

We thank Prof. F. Muguruza-Ugarte for his controversial although inspiring comments.

Funding information

This study has been funded by project PI14/00508 (Instituto de Salud Carlos III. Madrid, Spain) and by Fondo Europeo de Desarrollo Regional (FEDER) funds: “Una manera de hacer Europa”. J.M.A.-M. is partially supported by the Instituto de Salud Carlos III (Madrid, Spain) with a Miguel Servet fellowship and a specific grant (Acción Estratégica en Salud, PI14/00508). The Diputación General de Aragón (Spain) also provided financial support to this project.

Compliance with ethical standards

This study was approved by our local Institutional Review Board, the Comité de Ética de la Investigación de la Comunidad de Aragón (CEICA), and informed consent was obtained from all participants and/or their legal guardians.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13105_2018_638_MOESM1_ESM.pdf (80 kb)
Supplemental Figure 1 (PDF 79 kb)

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Copyright information

© University of Navarra 2018

Authors and Affiliations

  • Sergio Perez-Diaz
    • 1
  • Maria P. Garcia-Sobreviela
    • 1
  • Yolanda Gonzalez-Irazabal
    • 2
  • Beatriz Garcia-Rodriguez
    • 2
  • Silvia Espina
    • 1
    • 3
  • Izaskun Arenaz
    • 4
  • Jose M. Arbones-Mainar
    • 1
    • 5
  1. 1.Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Instituto de Investigación Sanitaria (IIS) AragónHospital Universitario Miguel ServetZaragozaSpain
  2. 2.Servicio de Bioquímica ClínicaHospital Universitario Miguel ServetZaragozaSpain
  3. 3.Servicio de Aparato DigestivoHospital Universitario Miguel ServetZaragozaSpain
  4. 4.Biobanco del Sistema de Salud de AragónInstituto Aragonés de Ciencias de la Salud (IACS)ZaragozaSpain
  5. 5.CIBER Fisiopatología Obesidad y Nutrición (CIBERObn)Instituto Salud Carlos IIIMadridSpain

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