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Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat

Author

Listed:
  • Takahiro Seki

    (Tumor and Cell Biology, Karolinska Institute)

  • Kayoko Hosaka

    (Tumor and Cell Biology, Karolinska Institute)

  • Sharon Lim

    (Tumor and Cell Biology, Karolinska Institute)

  • Carina Fischer

    (Tumor and Cell Biology, Karolinska Institute)

  • Jennifer Honek

    (Tumor and Cell Biology, Karolinska Institute)

  • Yunlong Yang

    (Tumor and Cell Biology, Karolinska Institute)

  • Patrik Andersson

    (Tumor and Cell Biology, Karolinska Institute)

  • Masaki Nakamura

    (Tumor and Cell Biology, Karolinska Institute)

  • Erik Näslund

    (Danderyd Hospital, Karolinska Institute)

  • Seppo Ylä-Herttuala

    (A.I. Virtanen Institute, Molecular Sciences University of Eastern Finland)

  • Meili Sun

    (Tumor and Cell Biology, Karolinska Institute)

  • Hideki Iwamoto

    (Tumor and Cell Biology, Karolinska Institute)

  • Xuri Li

    (State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University)

  • Yizhi Liu

    (State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University)

  • Nilesh J. Samani

    (University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital)

  • Yihai Cao

    (Tumor and Cell Biology, Karolinska Institute
    University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital)

Abstract

Cold- and β3-adrenoceptor agonist-induced sympathetic activation leads to angiogenesis and UCP1-dependent thermogenesis in mouse brown and white adipose tissues. Here we show that endothelial production of PDGF-CC during white adipose tissue (WAT) angiogenesis regulates WAT browning. We find that genetic deletion of endothelial VEGFR2, knockout of the Pdgf-c gene or pharmacological blockade of PDGFR-α impair the WAT-beige transition. We further show that PDGF-CC stimulation upregulates UCP1 expression and acquisition of a beige phenotype in differentiated mouse WAT-PDGFR-α+ progenitor cells, as well as in human WAT-PDGFR-α+ adipocytes, supporting the physiological relevance of our findings. Our data reveal a paracrine mechanism by which angiogenic endothelial cells modulate adipocyte metabolism, which may provide new targets for the treatment of obesity and related metabolic diseases.

Suggested Citation

  • Takahiro Seki & Kayoko Hosaka & Sharon Lim & Carina Fischer & Jennifer Honek & Yunlong Yang & Patrik Andersson & Masaki Nakamura & Erik Näslund & Seppo Ylä-Herttuala & Meili Sun & Hideki Iwamoto & Xur, 2016. "Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat," Nature Communications, Nature, vol. 7(1), pages 1-16, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12152
    DOI: 10.1038/ncomms12152
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