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Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans

Author

Listed:
  • Andrew J. Whittle

    (University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science)

  • Meizi Jiang

    (Toho University, Sakura Medical Center
    Chiba University Graduate School of Medicine)

  • Vivian Peirce

    (University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science)

  • Joana Relat

    (School of Pharmacy, University of Barcelona, and Institute of Biomedicine of the University of Barcelona (IBUB))

  • Sam Virtue

    (University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science)

  • Hiroyuki Ebinuma

    (Tsukuba Research Institute, Sekisui Medical Co. Ltd.)

  • Isamu Fukamachi

    (Tsukuba Research Institute, Sekisui Medical Co. Ltd.)

  • Takashi Yamaguchi

    (Center for Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center)

  • Mao Takahashi

    (Cardiovascular Center, Toho University, Sakura Medical Center)

  • Takeyoshi Murano

    (Toho University, Sakura Medical Center)

  • Ichiro Tatsuno

    (Center for Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center)

  • Masahiro Takeuchi

    (Chiba University Hospital)

  • Chiaki Nakaseko

    (Chiba University Hospital)

  • Wenlong Jin

    (Affiliated Hospital of Yanbian University)

  • Zhehu Jin

    (Affiliated Hospital of Yanbian University)

  • Mark Campbell

    (University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science)

  • Wolfgang J. Schneider

    (Medical University of Vienna, Max F. Perutz Laboratories)

  • Antonio Vidal-Puig

    (University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science
    Wellcome Trust Sanger Institute)

  • Hideaki Bujo

    (Toho University, Sakura Medical Center
    Chiba University Graduate School of Medicine)

Abstract

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFβ signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.

Suggested Citation

  • Andrew J. Whittle & Meizi Jiang & Vivian Peirce & Joana Relat & Sam Virtue & Hiroyuki Ebinuma & Isamu Fukamachi & Takashi Yamaguchi & Mao Takahashi & Takeyoshi Murano & Ichiro Tatsuno & Masahiro Takeu, 2015. "Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9951
    DOI: 10.1038/ncomms9951
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