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

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 () and Aimin Xu ()
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Kang Chen: The University of Hong Kong
Lai Yee Cheong: The University of Hong Kong
Yuan Gao: The University of Hong Kong
Yaming Zhang: The University of Hong Kong
Tianshi Feng: The University of Hong Kong
Qin Wang: The University of Hong Kong
Leigang Jin: 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
Weiping Wang: The University of Hong Kong
Xiaoyan Hui: The University of Hong Kong
Aimin Xu: The University of Hong Kong

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35470-4

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