IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35470-4.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35470-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35470-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Amar M. Singh & Liang Zhang & John Avery & Amelia Yin & Yuhong Du & Hui Wang & Zibo Li & Haian Fu & Hang Yin & Stephen Dalton, 2020. "Human beige adipocytes for drug discovery and cell therapy in metabolic diseases," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Ruth S.M. Chan & Jean Woo, 2010. "Prevention of Overweight and Obesity: How Effective is the Current Public Health Approach," IJERPH, MDPI, vol. 7(3), pages 1-19, February.
    3. Alexander Bartelt & Clara John & Nicola Schaltenberg & Jimmy F. P. Berbée & Anna Worthmann & M. Lisa Cherradi & Christian Schlein & Julia Piepenburg & Mariëtte R. Boon & Franz Rinninger & Markus Heine, 2017. "Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    4. Huating Li & Guangyu Wu & Qichen Fang & Mingliang Zhang & Xiaoyan Hui & Bin Sheng & Liang Wu & Yuqian Bao & Peng Li & Aimin Xu & Weiping Jia, 2018. "Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    5. Jean-Pierre Després & Isabelle Lemieux, 2006. "Abdominal obesity and metabolic syndrome," Nature, Nature, vol. 444(7121), pages 881-887, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hsin-Han Chen & Hui-Ling Chen & Yi-Tien Lin & Chaou-Wen Lin & Chien-Chang Ho & Hsueh-Yi Lin & Po-Fu Lee, 2020. "The Associations between Functional Fitness Test Performance and Abdominal Obesity in Healthy Elderly People: Results from the National Physical Fitness Examination Survey in Taiwan," IJERPH, MDPI, vol. 18(1), pages 1-14, December.
    2. Saaket Agrawal & Marcus D. R. Klarqvist & Nathaniel Diamant & Takara L. Stanley & Patrick T. Ellinor & Nehal N. Mehta & Anthony Philippakis & Kenney Ng & Melina Claussnitzer & Steven K. Grinspoon & Pu, 2023. "BMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Dionysios V Chartoumpekis & Apostolos Zaravinos & Panos G Ziros & Ralitsa P Iskrenova & Agathoklis I Psyrogiannis & Venetsana E Kyriazopoulou & Ioannis G Habeos, 2012. "Differential Expression of MicroRNAs in Adipose Tissue after Long-Term High-Fat Diet-Induced Obesity in Mice," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-13, April.
    4. Purificación Gómez-Abellán & Antoni Díez-Noguera & Juan A Madrid & Juan A Luján & José M Ordovás & Marta Garaulet, 2012. "Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-10, December.
    5. Sofia I I Kring & Claus Holst & Esther Zimmermann & Tine Jess & Tina Berentzen & Søren Toubro & Torben Hansen & Arne Astrup & Oluf Pedersen & Thorkild I A Sørensen, 2008. "FTO Gene Associated Fatness in Relation to Body Fat Distribution and Metabolic Traits throughout a Broad Range of Fatness," PLOS ONE, Public Library of Science, vol. 3(8), pages 1-7, August.
    6. Ming Zhao & Hongbo Lin & Yanyan Yuan & Fuyan Wang & Yang Xi & Li Ming Wen & Peng Shen & Shizhong Bu, 2016. "Prevalence of Pre-Diabetes and Its Associated Risk Factors in Rural Areas of Ningbo, China," IJERPH, MDPI, vol. 13(8), pages 1-13, August.
    7. Katharina Ruettger & Stacy A. Clemes & Yu-Ling Chen & Charlotte L. Edwardson & Amber Guest & Nicholas D. Gilson & Laura J. Gray & Vicki Johnson & Nicola J. Paine & Aron P. Sherry & Mohsen Sayyah & Jac, 2022. "Drivers with and without Obesity Respond Differently to a Multi-Component Health Intervention in Heavy Goods Vehicle Drivers," IJERPH, MDPI, vol. 19(23), pages 1-12, November.
    8. Shih-Chang Chen & Chaou-Wen Lin & Po-Fu Lee & Hui-Ling Chen & Chien-Chang Ho, 2021. "Anthropometric Characteristics in Taiwanese Adults: Age and Gender Differences," IJERPH, MDPI, vol. 18(14), pages 1-13, July.
    9. Aimee M. Deaton & Aditi Dubey & Lucas D. Ward & Peter Dornbos & Jason Flannick & Elaine Yee & Simina Ticau & Leila Noetzli & Margaret M. Parker & Rachel A. Hoffing & Carissa Willis & Mollie E. Plekan , 2022. "Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Qi Zhu & Kun Xue & Hong Wei Guo & Fei Fei Deng & Yu Huan Yang, 2020. "Interaction of the CMTM7 rs347134 Polymorphism with Dietary Patterns and the Risk of Obesity in Han Chinese Male Children," IJERPH, MDPI, vol. 17(5), pages 1-15, February.
    11. Ashley Beckett & Jake Riley Scott & Angel Marie Chater & Louise Ferrandino & Jeffrey William Frederick Aldous, 2023. "The Prevalence of Metabolic Syndrome and Its Components in Firefighters: A Systematic Review and Meta-Analysis," IJERPH, MDPI, vol. 20(19), pages 1-14, September.
    12. Müller, Nathalie & Fallucchi, Francesco & Suhrcke, Marc, 2024. "Peer effects in weight-related behaviours of young people: A systematic literature review," Economics & Human Biology, Elsevier, vol. 53(C).
    13. Vincenzo Sicari & Irene Maria Grazia Custureri & Rosa Tundis & Monica Rosa Loizzo, 2023. "Comparison of Physicochemical Characteristics and Bioactivity of Olive Oil Mill Wastewaters from Traditional and Water-Saving ARA-Controlled Three-Phase Decanter," Sustainability, MDPI, vol. 15(5), pages 1-11, February.
    14. Hashem Salarzadeh Jenatabadi & Che Wan Jasimah Bt Wan Mohamed Radzi & Nadia Samsudin, 2020. "Associations of Body Mass Index with Demographics, Lifestyle, Food Intake, and Mental Health among Postpartum Women: A Structural Equation Approach," IJERPH, MDPI, vol. 17(14), pages 1-24, July.
    15. Dorothea Kesztyüs & Romy Lauer & Tibor Kesztyüs & Reinhold Kilian & Jürgen M Steinacker & on behalf of the “Join the Healthy Boat” Study Group, 2017. "Costs and effects of a state-wide health promotion program in primary schools in Germany – the Baden-Württemberg Study: A cluster-randomized, controlled trial," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-18, February.
    16. Shamim Shaikh Mohiuddin, 2019. "A Mini Review on Diagnostic Criteria of Metabolic Syndrome Associated with Chronic Obesity in Children and Adolescent," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 9(3), pages 72-77, January.
    17. Hicken, Margaret T. & Lee, Hedwig & Hing, Anna K., 2018. "The weight of racism: Vigilance and racial inequalities in weight-related measures," Social Science & Medicine, Elsevier, vol. 199(C), pages 157-166.
    18. Ha-Jin Jang & Hannah Oh, 2021. "Trends and Inequalities in Overall and Abdominal Obesity by Sociodemographic Factors in Korean Adults, 1998–2018," IJERPH, MDPI, vol. 18(8), pages 1-19, April.
    19. Furong Xu & Jacob E. Earp & Alessandra Adami & Ingrid E. Lofgren & Matthew J. Delmonico & Geoffrey W. Greene & Deborah Riebe, 2022. "The Sex and Race/Ethnicity-Specific Relationships of Abdominal Fat Distribution and Anthropometric Indices in US Adults," IJERPH, MDPI, vol. 19(23), pages 1-12, November.
    20. Jongnam Hwang & Eun-Young Lee & Chung Gun Lee, 2019. "Measuring Socioeconomic Inequalities in Obesity among Korean Adults, 1998–2015," IJERPH, MDPI, vol. 16(9), pages 1-14, May.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35470-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.