2. Academic Validation
  3. Adipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects

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

  • Nat Commun. 2022 Dec 20;13(1):7838. doi: 10.1038/s41467-022-35470-4.
Kang Chen 1 2 3,  Lai Yee Cheong 1 2,  Yuan Gao 1 2,  Yaming Zhang 1 3 4,  Tianshi Feng 1 2,  Qin Wang 1 2,  Leigang Jin 1 2,  Eric Honoré 5,  Karen S L Lam 1 2,  Weiping Wang 6 7 8,  Xiaoyan Hui 9 10,  Aimin Xu 11 12
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Laboratory Block, Pokfulam, Hong Kong, China.
  • 2 Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • 3 Dr Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • 4 Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • 5 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, Valbonne, France.
  • 6 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Laboratory Block, Pokfulam, Hong Kong, China. wangwp@hku.hk.
  • 7 Dr Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. wangwp@hku.hk.
  • 8 Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. wangwp@hku.hk.
  • 9 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Laboratory Block, Pokfulam, Hong Kong, China. hannahui@hku.hk.
  • 10 Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. hannahui@hku.hk.
  • 11 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Laboratory Block, Pokfulam, Hong Kong, China. amxu@hku.hk.
  • 12 Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. amxu@hku.hk.
PMID: 36539421 DOI: 10.1038/s41467-022-35470-4
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.

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