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

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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.

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


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.

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Correspondence to Jose M. Arbones-Mainar.

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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.

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The authors declare that they have no conflict of interest.

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Perez-Diaz, S., Garcia-Sobreviela, M.P., Gonzalez-Irazabal, Y. et al. PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition. J Physiol Biochem 74, 613–622 (2018).

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