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Adipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects

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  • Kang Chen

    (The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong)

  • Lai Yee Cheong

    (The University of Hong Kong
    The University of Hong Kong)

  • Yuan Gao

    (The University of Hong Kong
    The University of Hong Kong)

  • Yaming Zhang

    (The University of Hong Kong
    The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong
    The University of Hong Kong)

  • Tianshi Feng

    (The University of Hong Kong
    The University of Hong Kong)

  • Qin Wang

    (The University of Hong Kong
    The University of Hong Kong)

  • Leigang Jin

    (The University of Hong Kong
    The University of Hong Kong)

  • Eric Honoré

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Karen S. L. Lam

    (The University of Hong Kong
    The University of Hong Kong)

  • Weiping Wang

    (The University of Hong Kong
    The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong
    The University of Hong Kong)

  • Xiaoyan Hui

    (The University of Hong Kong
    The University of Hong Kong)

  • Aimin Xu

    (The University of Hong Kong
    The University of Hong Kong)

Abstract

Thyroid hormone (TH) is a thermogenic activator with anti-obesity potential. However, systemic TH administration has no obvious clinical benefits on weight reduction. Herein we selectively delivered triiodothyronine (T3) to adipose tissues by encapsulating T3 in liposomes modified with an adipose homing peptide (PLT3). Systemic T3 administration failed to promote thermogenesis in brown and white adipose tissues (WAT) due to a feedback suppression of sympathetic innervation. PLT3 therapy effectively obviated this feedback suppression on adrenergic inputs, and potently induced browning and thermogenesis of WAT, leading to alleviation of obesity, glucose intolerance, insulin resistance, and fatty liver in obese mice. Furthermore, PLT3 was much more effective than systemic T3 therapy in reducing hypercholesterolemia and atherosclerosis in apoE-deficient mice. These findings uncover WAT as a viable target mediating the therapeutic benefits of TH and provide a safe and efficient therapeutic strategy for obesity and its complications by delivering TH to adipose tissue.

Suggested Citation

  • Kang Chen & Lai Yee Cheong & Yuan Gao & Yaming Zhang & Tianshi Feng & Qin Wang & Leigang Jin & Eric Honoré & Karen S. L. Lam & Weiping Wang & Xiaoyan Hui & Aimin Xu, 2022. "Adipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35470-4
    DOI: 10.1038/s41467-022-35470-4
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