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Cellular and Molecular Life Sciences

, Volume 76, Issue 24, pp 5011–5025 | Cite as

PGC-1α induced browning promotes involution and inhibits lactation in mammary glands

  • Elena Piccinin
  • Annalisa Morgano
  • Claudia Peres
  • Annalisa Contursi
  • Justine Bertrand-Michel
  • Maria Arconzo
  • Hervé Guillou
  • Gaetano Villani
  • Antonio MoschettaEmail author
Original Article

Abstract

The PPARγ coactivator 1α (PGC-1α) is a transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. Recent studies have highlighted a fundamental role of PGC-1α in promoting breast cancer progression and metastasis, but the physiological role of this coactivator in the development of mammary glands is still unknown. First, we show that PGC-1α is highly expressed during puberty and involution, but nearly disappeared in pregnancy and lactation. Then, taking advantage of a newly generated transgenic mouse model with a stable and specific overexpression of PGC-1α in mammary glands, we demonstrate that the re-expression of this coactivator during the lactation stage leads to a precocious regression of the mammary glands. Thus, we propose that PGC-1α action is non-essential during pregnancy and lactation, whereas it is indispensable during involution. The rapid preadipocyte–adipocyte transition, together with an increased rate of apoptosis promotes a premature mammary glands involution that cause lactation defects and pup growth retardation. Overall, we provide new insights in the comprehension of female reproductive cycles and lactation deficiency, thus opening new roads for mothers that cannot breastfeed.

Keywords

Mammary glands Nuclear receptor Coactivator Development Adipocytes Involution 

Abbreviations

PGC-1

Peroxisome proliferator-activated receptor gamma coactivator 1

UCP1

Uncoupling protein 1

TFAM

Mitochondrial transcription factor A

Mmtv

Mouse mammary tumor virus

Notes

Acknowledgements

We thank L. Salvatore and G. Di Tullio, for their invaluable help during the study, and J-M. Lobaccaro and J. Hardfeldth, for their help with the manuscript. A. Moschetta is funded by Italian Association for Cancer Research (AIRC, IG 18987), NR-NET FP7 Marie Curie People ITN and EU-JPI FATMAL 2017.

Author contributions

EP contributed to study design, performed experiments, analysed data and wrote the paper; AM contributed to study design, performed experiments and data analysis; CP, AC, JBM, MA and HG performed experiments; GV contributed to paper writing; AM designed the study, supervised the project and paper writing.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

Ethics statement

The Ethical Committee of the Consorzio Mario Negri Sud and the University of Bari approved this experimental set-up, which also was certified by the Italian Ministry of Health in accordance with internationally accepted guidelines for animal care.

Supplementary material

18_2019_3160_MOESM1_ESM.tif (5.2 mb)
Supplementary Fig. 1 PGC-1α overexpression affects pups development. (A) hPGC-1α (white bars) and mPGC-1α (black bar) relative mRNA expression in different tissue specimens isolated from transgenic and wild type mice (n = 6) by real-time qPCR. TBP was used as housekeeping gene to normalize data and wild type mice was used as calibrators. Results are expressed as mean ± SEM. (B) Picture of wild-type and mmtvPGC-1α newborns at 21 days after birth. (C) Picture of wild type and mmtvPGC-1α newborns at 19 days after birth fostered by mmtvPGC-1α and wild-type mother, respectively. (TIFF 5283 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Elena Piccinin
    • 1
  • Annalisa Morgano
    • 1
  • Claudia Peres
    • 1
    • 2
  • Annalisa Contursi
    • 3
  • Justine Bertrand-Michel
    • 4
  • Maria Arconzo
    • 2
  • Hervé Guillou
    • 5
  • Gaetano Villani
    • 6
  • Antonio Moschetta
    • 1
    • 7
    Email author
  1. 1.Department of Interdisciplinary Medicine“Aldo Moro” University of BariBariItaly
  2. 2.INBB, National Institute for Biostuctures and BiosystemsRomeItaly
  3. 3.Department of Neuroscience, Imaging and Clinical Sciences and Center for Research on Aging and Translational Medicine (CeSI-MeT)“G. d’Annunzio” University of ChietiChietiItaly
  4. 4.MetaToul-Lipidomic Facility-MetaboHUB, INSERM UMR1048Institute of Cardiovascular and Metabolic Diseases, Université Paul SabatierToulouseFrance
  5. 5.Toxalim (Research Centre in Food Toxicology), Université de ToulouseUMR1331 INRA, ENVT, INP-Purpan, Université Paul SabatierToulouseFrance
  6. 6.Department of Basic Medical Sciences, Neurosciences and Sense Organs“Aldo Moro” University of BariBariItaly
  7. 7.National Cancer CenterIRCCS Istituto Tumori “Giovanni Paolo II”BariItaly

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