Central vs. Peripheral Action of Thyroid Hormone in Adaptive Thermogenesis: A Burning Topic
Open accessAbstract
Thyroid hormones (TH) contribute to the control of adaptive thermogenesis, which is associated with both higher energy expenditure and lower body mass index. While it was clearly established that TH act directly in the target tissues to fulfill its metabolic activities, some studies have rather suggested that TH act in the hypothalamus to control these processes. This paradigm shift has subjected the topic to intense debates. This review aims to recapitulate how TH control adaptive thermogenesis and to what extent the brain is involved in this process. This is of crucial importance for the design of new pharmacological agents that would take advantage of the TH metabolic properties.
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Caloric restriction reduces circulating levels of T3 and T4.
“Caloric restriction reduces the circulating levels of triiodothyronine (T3), the active form of thyroid hormone, while thyroxine (T4) also drops.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [30]
Ghrelin rises during caloric restriction.
“Ghrelin, primarily produced by the stomach, rises during caloric restriction [30].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [30]
A reduction in T3 results from downregulation of the type II iodothyronine deiodinase enzyme, which normally converts T4 into T3 in peripheral tissues.
“A reduction in T3 results from downregulation of the type II iodothyronine deiodinase enzyme, which normally converts T4 into T3 in peripheral tissues.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [30]
Lowered T3 reduces mitochondrial biogenesis, oxidative phosphorylation, and basal thermogenesis, impacting energy expenditure of key tissues.
“Lowered T3 also reduces mitochondrial biogenesis, oxidative phosphorylation, and basal thermogenesis, impacting the energy expenditure of key tissues.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [30]
Reductions in BMR during caloric restriction (adaptive thermogenesis) vary widely due to differences in thyroid hormone metabolism.
“As already analyzed, reductions in the BMR during caloric restriction, known as adaptive thermogenesis, vary widely due to differences in thyroid hormone metabolism.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [30]
Lowered thyroid hormones, particularly T3, reduce metabolic rate by downregulating mitochondrial biogenesis and ATP turnover.
“Lowered thyroid hormones, particularly T3, reduce metabolic rate by downregulating mitochondrial biogenesis and ATP turnover [25,26,30].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [30]
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Fleishman, J. S., & Kumar, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01811-6 · Cited by 577 · see citing works
The ecological function of thyroid hormones
Zwahlen, J., Gairin, E., Vianello, S., Mercader, M., Roux, N., & Laudet, V. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2022.0511 · Cited by 73 · see citing works
Thyroid Detection and Classification Using DNN Based on Hybrid Meta-Heuristic and LSTM Technique
Mohan, E., Saravanan, P., Natarajan, B., Kumer, S. V. A., Sambasivam, G., Kanna, G. P., & Tyagi, V. B. (2023) · IEEE Access · doi:10.1109/access.2023.3289511 · Cited by 48 · see citing works
Theodorakis, N., Kreouzi, M., Pappas, A., & Nikolaou, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413438 · Cited by 43 · see citing works
Sex Dimorphic Responses of the Hypothalamus-Pituitary-Thyroid Axis to Energy Demands and Stress
de, M. A. P.-M., Sotelo-Rivera, I., Gutiérrez-Mata, A., Charli, J., & Joseph‐Bravo, P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.746924 · Cited by 39 · see citing works
Lezama-García, K., Mota‐Rojas, D., Martı́nez-Burnes, J., Villanueva‐García, D., Domínguez-Oliva, A., Gómez-Prado, J., Mora‐Medina, P., Casas-Alvarado, A., Olmos-Hernández, A. S., Soto, P., et al. (2022) · Veterinary Sciences · doi:10.3390/vetsci9050246 · Cited by 34 · see citing works
Physical exercise for a healthy pregnancy: the role of placentokines and exerkines
Pahlavani, H. A., Laher, I., Weiss, K., Knechtle, B., & Zouhal, H. (2023) · The Journal of Physiological Sciences · doi:10.1186/s12576-023-00885-1 · Cited by 31 · see citing works
The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis
Sawicka‐Gutaj, N., Erampamoorthy, A., Zybek‐Kocik, A., Kyriacou, A., Zgorzalewicz-Stachowiak, M., Czarnywojtek, A., & Ruchała, M. (2022) · Metabolites · doi:10.3390/metabo12040336 · Cited by 21 · see citing works
Possible roles of exercise and apelin against pregnancy complications
Pahlavani, H. A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.965167 · Cited by 19 · see citing works
Rial‐Pensado, E., Canaple, L., Guyot, R., Clemmensen, C., Wiersema, J., Wu, S., Richard, S., Boelen, A., Müller, T. D., López, M., et al. (2023) · Endocrinology · doi:10.1210/endocr/bqad034 · Cited by 10 · see citing works
Self-citationNeuroendocrine control of brown adipocyte function by prolactin and growth hormone
Winne, C. D., Pascual, F. L., Lopez‐Vicchi, F., Boneo, L. E., Mendez‐Garcia, L. F., Ornstein, A. M., Lacau-Mengido, I. M., Sorianello, E. M., & Becú‐Villalobos, D. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13248 · Cited by 10 · see citing works
Liu, J., Song, R., Pan, R., Yi, W., Jin, X., Song, J. G., Cheng, J., Zhang, X., & Su, H. (2024) · Environment International · doi:10.1016/j.envint.2024.108961 · Cited by 9 · see citing works
The complexity of the relationship between thyroid disease and body weight
Jonklaas, J. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01190-0 · Cited by 9 · see citing works
Bardová, K., Janovská, P., Vavrova, A., Kopecky, J., & Zouhar, P. (2024) · Physiological Research · doi:10.33549/physiolres.935361 · Cited by 9 · see citing works
Comparative analysis of thyroid hormone systems in rodents with subterranean lifestyle
Gerhardt, P., Begall, S., Frädrich, C., Renko, K., Hildebrandt, T. B., Holtze, S., Heinrich, A., Sahm, A., Meçi, X., Köhrle, J., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-30179-w · Cited by 8 · see citing works
Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase
Capelli, V., Grijota-Martínez, C., Dragano, N. R. V., Rial‐Pensado, E., Fernø, J., Nogueiras, R., Mittag, J., Diéguez, C., & López, M. (2021) · Nutrients · doi:10.3390/nu13124204 · Cited by 7 · see citing works
Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA
Zeng, T., Xiao, L., Li, J., Wu, H., Guo, X., Zhu, F., Yu, X., Cui, Y., Zhao, X., Wang, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62740-8 · Cited by 6 · see citing works
Romero-Ibarguengoitia, M. E., Garza‐Silva, A., Rivera-Cavazos, A., Morales-Rodríguez, D. P., Peña, O. I. G., Barco-Flores, I. A., Manilla-Muñoz, E., Villarreal-Leal, E., & González‐Cantú, A. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad175 · Cited by 6 · see citing works
Thyroid Hormone Signaling and Function: News from Classical and Emerging Models
Sirakov, M., & Plateroti, M. (2022) · Cells · doi:10.3390/cells11030453 · Cited by 3 · see citing works
Hernández, A., & Celi, F. S. (2026) · Journal of Clinical Investigation · doi:10.1172/jci205029 · Cited by 1 · see citing works
Costa-e-Sousa, R. H., & Brooks, V. L. (2024) · Vitamins and hormones · doi:10.1016/bs.vh.2024.07.005 · Cited by 1 · see citing works
The Complexities of Metabolic Flexibility and Precision Approaches to Sustainable Weight Management
Theodorakis, N., Kreouzi, M., Pappas, A., Feretzakis, G., Sakagianni, A., Kalodanis, K., Αναστασίου, Α., Nikolaou, M., & Koumpouros, Y. (2025) · IGI Global eBooks · doi:10.4018/979-8-3693-5787-3.ch005
BCAA catabolism in TRH neurons of paraventricular nucleus regulates energy expenditure
Ming, X., Tan, J., Yuan, M., Ma, X., Zhou, F., Wang, S., Lyu, Q., Xue, W., Bo, T., Liu, Y., et al. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156435
Gènes cibles des hormones thyroïdiennes, un regard nouveau par le prisme des analyses pangénomiques
Zekri, Y. (2022) · theses.fr (ABES) · doi:10.70675/f8d646ffzf184z40e1z848az174a3d652f5d
Self-citationPregnancy negates thyroid hormone-induced pyrexia
López‐Alcántara, N., Adam, L., Resch, J., Keipert, S., Mittag, J., & Oelkrug, R. (2026) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00569.2025
Calcaterra, V., Labati, L., Scavone, I. A. M., Scelsa, B., Veggiotti, P., & Zuccotti, G. (2026) · European Journal of Pediatrics · doi:10.1007/s00431-026-07045-8
Ferraretti, G., Alberti, M., Cicolini, R., Viù, S. P., Sarno, S., & Sazzini, M. (2026) · Communications Biology · doi:10.1038/s42003-026-10540-1
Esin, E. V., Bush, A. G., Маркевич, Г. Н., & Shkil, F. N. (2026) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.70034
Zahorodnii, A., Jelska, A., Głuszyńska, P., Almltashe, L. M. M., & Hady, H. R. (2026) · Nutrients · doi:10.3390/nu18193287
- Authors
- Zekri, Y., Flamant, F., & Gauthier, K.
- Affiliations
- Lyon 1 Université (FR)
- Corresponding author
- Zekri, Yanis
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2021-05-27
- Volume
- 10
- Issue
- 6
- Pages
- 1327
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC8229489
- OpenAlex
- W3164386179
- Cited by
- 27
- References
- 178
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 5 · 2021: 2
- FWCI
- 0.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (825753)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
- Horizon 2020 Framework Programme (825753)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- thyroid hormones, adaptive thermogenesis, hypothalamus, energy expenditure, body mass index, brain thermoregulation
- MeSH terms
- Adipose Tissue, Brown, Energy Metabolism, Humans, Hypothalamus, Thyroid Hormones, Thermogenesis, Adipose Tissue, White
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