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A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes

Author

Listed:
  • Lingling Shu

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

  • Ruby L. C. Hoo

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

  • Xiaoping Wu

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

  • Yong Pan

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

  • Ida P. C. Lee

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

  • Lai Yee Cheong

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

  • Stefan R Bornstein

    (University of Dresden)

  • Xianglu Rong

    (Joint Laboratory of Guangdong and Hong Kong on Metabolic Diseases, Guangdong Pharmaceutical University)

  • Jiao Guo

    (Joint Laboratory of Guangdong and Hong Kong on Metabolic Diseases, Guangdong Pharmaceutical University)

  • Aimin Xu

    (State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong
    LKS Faculty of Medicine, The University of Hong Kong)

Abstract

The adipokine adipocyte fatty acid-binding protein (A-FABP) has been implicated in obesity-related cardio-metabolic complications. Here we show that A-FABP increases thermogenesis by promoting the conversion of T4 to T3 in brown adipocytes. We find that A-FABP levels are increased in both white (WAT) and brown (BAT) adipose tissues and the bloodstream in response to thermogenic stimuli. A-FABP knockout mice have reduced thermogenesis and whole-body energy expenditure after cold stress or after feeding a high-fat diet, which can be reversed by infusion of recombinant A-FABP. Mechanistically, A-FABP induces the expression of type-II iodothyronine deiodinase in BAT via inhibition of the nuclear receptor liver X receptor α, thereby leading to the conversion of thyroid hormone from its inactive form T4 to active T3. The thermogenic responses to T4 are abrogated in A-FABP KO mice, but enhanced by A-FABP. Thus, A-FABP acts as a physiological stimulator of BAT-mediated adaptive thermogenesis.

Suggested Citation

  • Lingling Shu & Ruby L. C. Hoo & Xiaoping Wu & Yong Pan & Ida P. C. Lee & Lai Yee Cheong & Stefan R Bornstein & Xianglu Rong & Jiao Guo & Aimin Xu, 2017. "A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes," Nature Communications, Nature, vol. 8(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14147
    DOI: 10.1038/ncomms14147
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    Cited by:

    1. Tatsuya Yoshizawa & Yoshifumi Sato & Shihab U. Sobuz & Tomoya Mizumoto & Tomonori Tsuyama & Md. Fazlul Karim & Keishi Miyata & Masayoshi Tasaki & Masaya Yamazaki & Yuichi Kariba & Norie Araki & Eiichi, 2022. "SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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