Leptin Administration Restores the Fasting-Induced Increase of Hepatic Type 3 Deiodinase Expression in Mice
Abstract
BACKGROUND: Decreased serum leptin has been proposed as a critical signal initiating the neuroendocrine response to fasting. Leptin administration partially reverses the fasting-induced suppression of the hypothalamus-pituitary-thyroid axis at the central level. It is, however, unknown to what extent leptin affects peripheral thyroid hormone metabolism. The aim of this study was to evaluate the effect of leptin administration on starvation-induced alterations of peripheral thyroid hormone metabolism in mice. METHODS: Three types of experiments were performed: (i) mice were fasted for 24 hours while leptin was administered twice (at 0 and 8 hours, 1 μg/g body weight [BW]), (ii) mice were fasted for 24 hours and, subsequently, leptin was given once at 24 hours (killed at 28 and 32 hours), and (iii) mice were fasted for 48 hours. All groups had appropriate controls. Serum triiodothyronine and thyroxine, liver type 1 deiodinase (D1), type 3 deiodinase (D3), thyroid hormone receptor (TR)β1, TRα1 and α2 mRNA expression, and liver D1 and D3 activity were measured. RESULTS: Twenty-four hours of fasting decreased liver TRβ1 mRNA expression, while liver TRα1, TRα2, and D1 mRNA expression and activity did not change. In contrast, 24 hours of fasting increased liver D3 mRNA. Leptin administration after fasting restored liver D3 expression, while serum thyroid hormone levels and liver TRβ1 expression remained low. CONCLUSION: Leptin administration selectively restores starvation-induced increased hepatic D3 expression independently of serum thyroid hormone concentrations. The present study shows that fasting-induced changes in mRNA expression of genes involved in hepatic hormone metabolism are influenced not only by decreased serum thyroid hormone levels but also by serum leptin.
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The response of DIO3 to illness might depend on energy status; fasting results in increased liver DIO3 activity in rodents and prolonged illness is associated with diminished food intake.
“The response of DIO3 to illness might depend on energy status; fasting results in increased liver DIO3 activity in rodents [23, 24] and prolonged illness is associated with diminished food intake [25].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [23]
Cites
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117 · see citing works
Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data
Ruijter, J. M., Ramakers, C., Hoogaars, W. M. H., Karlen, Y., Bakker, O., van den Hoff, M. J. B., & Moorman, A. F. M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp045 · Cited by 3,043 · see citing works
Activation of Downstream Signals by the Long Form of the Leptin Receptor
Banks, A. S., Davis, S. M., Bates, S. H., & Myers, M. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14563 · Cited by 797 · see citing works
Légrádi, G., Emerson, C. H., Ahima, R. S., Flier, J. S., & Lechan, R. M. (1997) · Endocrinology · doi:10.1210/en.138.6.2569 · Cited by 505 · see citing works
Peeters, R. P., Wouters, P. J., Kaptein, E., van Toor, H., Visser, T. J., & Van den Berghe, G. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-022013 · Cited by 452 · see citing works
The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism
Docter, R., Krenning, E. P., de Jong, M., & Hennemann, G. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb02401.x · Cited by 345 · see citing works
Kim, M. S., Small, C. J., Stanley, S. A., Morgan, D. G. A., Seal, L. J., Kong, W. M., Edwards, C. M. B., Abusnana, S., Sunter, D., Ghatei, M. A., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8857 · Cited by 256 · see citing works
Sweet, M. J., Leung, B. P. L., Kang, D., Søgaard, M., Schulz, K., Trajković, V., Campbell, C., Xu, D., & Liew, F. Y. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.11.6633 · Cited by 248 · see citing works
Critical role of STAT3 in leptin's metabolic actions
Buettner, C., Pocai, A., Muse, E. D., Etgen, A. M., Myers, M. G., & Rossetti, L. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.014 · Cited by 228 · cited 1× · see citing works
“Interestingly, leptin activates Jak2 and phosphorylates STAT3 and MAPK, respectively (28).”
Gereben, B., Zeöld, A., Dentice, M., Salvatore, D., & Bianco, A. C. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7396-0 · Cited by 207 · see citing works
Leptin Receptor Action in Hepatic Cells
Wang, Y., Kuropatwinski, K. K., White, D. W., Hawley, T. S., Hawley, R. G., Tartaglia, L. A., & Baumann, H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16216 · Cited by 196 · see citing works
Fasting-Induced Changes in the Hypothalamus–Pituitary–Thyroid Axis
Boelen, A., Wiersinga, W. M., & Fliers, E. (2008) · Thyroid · doi:10.1089/thy.2007.0253 · Cited by 194 · see citing works
Self-citationBoelen, A., Kwakkel, J., Thijssen-Timmer, D., Alkemade, A., Fliers, E., & Wiersinga, W. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1820315 · Cited by 159 · see citing works
Self-citationA RADIOIMMUNOASSAY OF THYROXINE
CHOPRA, I. J., SOLOMON, D. H., & HO, R. S. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-33-5-865 · Cited by 134 · see citing works
Boelen, A., Kwakkel, J., Alkemade, A., Renckens, R., Kaptein, E., Kuiper, G., Wiersinga, W. M., & Visser, T. J. (2005) · Endocrinology · doi:10.1210/en.2005-0608 · Cited by 117 · see citing works
Self-citationLiver Triglyceride Secretion and Lipid Oxidative Metabolism Are Rapidly Altered by Leptin in Vivo
Huang, W., Dedousis, N., Bandi, A., Lopaschuk, G. D., & O'Doherty, R. M. (2005) · Endocrinology · doi:10.1210/en.2005-0731 · Cited by 115 · see citing works
Wiersinga, W. M., & CHOPRA, I. J. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)84024-x · Cited by 100 · see citing works
Kumar, A., Middleton, A., Chambers, T. C., & Mehta, K. D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.25.15742 · Cited by 97 · see citing works
O'Mara, B. A., Dittrich, W., Lauterio, T. J., & Germain, D. L. S. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404614 · Cited by 93 · see citing works
Physiology and Pathophysiology of Type 3 Deiodinase in Humans
Huang, S. A. (2005) · Thyroid · doi:10.1089/thy.2005.15.875 · Cited by 92 · see citing works
Regulation of Type III Iodothyronine Deiodinase Expression in Human Cell Lines
Kester, M. H. A., Kuiper, G. G. J. M., Versteeg, R., & Visser, T. J. (2006) · Endocrinology · doi:10.1210/en.2006-0590 · Cited by 74 · see citing works
Sadow, P. M., Chassande, O., Koo, E. K., Gauthier, K. C., Samarut, J., Xu, J., O’Malley, B. W., & Weiss, R. E. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(03)00122-9 · Cited by 58 · see citing works
Animal Models of Nonthyroidal Disease*
Tibaldi, J. M., & Surks, M. I. (1985) · Endocrine Reviews · doi:10.1210/edrv-6-1-87 · Cited by 58 · see citing works
Leptin activates Stat3, Stat1 and AP-1 in mouse adipose tissue
Bendinelli, P., Maroni, P., Giraldi, F. P., & Piccoletti, R. (2000) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(00)00313-0 · Cited by 51 · see citing works
Oppenheimer, J. H., & Schwartz, H. L. (1980) · Endocrinology · doi:10.1210/endo-107-5-1460 · Cited by 50 · see citing works
Araújo, R. L., Andrade, B. M., da Silva, M. L., Ferreira, A. C. F., & de Carvalho, D. P. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90869.2008 · Cited by 50 · see citing works
Weekers, F., Michalaki, M. A., Coopmans, W., Herck, E. V., Veldhuis, J. D., Darras, V., & den Berghe, G. V. (2003) · Endocrinology · doi:10.1210/en.2003-1005 · Cited by 47 · see citing works
Boelen, A., Kwakkel, J., Vos, X. G., Wiersinga, W. M., & Fliers, E. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06872 · Cited by 36 · see citing works
Self-citationInterleukin-1β modulates endogenous thyroid hormone receptor α gene transcription in liver cells
Kwakkel, J., Wiersinga, W. M., & Boelen, A. (2007) · Journal of Endocrinology · doi:10.1677/joe-06-0177 · Cited by 34 · see citing works
Self-citationBoelen, A., Kwakkel, J., Chassande, O., & Fliers, E. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01863.x · Cited by 32 · see citing works
Self-citationZandieh‐Doulabi, B., Schiphorst, M. P.-T., Kalsbeek, A., Fliers, E., Bakker, O., & Wiersinga, W. M. (2003) · Endocrinology · doi:10.1210/en.2003-0791 · Cited by 21 · see citing works
Self-citationEffects of energy restriction on thyroid hormone metabolism in chickens
Győrffy, A., Sayed-Ahmed, A., Zsarnovszky, A., et al. (2009) · Acta Veterinaria Hungarica · doi:10.1556/avet.57.2009.2.12 · Cited by 17 · see citing works
Boelen, A., Schiphorst, M. P.-T., van Rooijen, N., & Wiersinga, W. M. (1996) · European Journal of Endocrinology · doi:10.1530/eje.0.1340513 · Cited by 12 · see citing works
Self-citationFasting Induces a Decrease in Serum Thyroglobulin in Normal Subjects*
UNGER, J. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-6-1309 · Cited by 10 · see citing works
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Van den Berghe, G. (2014) · Thyroid® · doi:10.1089/thy.2014.0201 · Cited by 316 · see citing works
Paradigms of dynamic control of thyroid hormone signaling
Bianco, A. C., Dumitrescu, A., Gereben, B., Ribeiro, M. O., Fonseca, T. L., Fernandes, G. W., & Bocco, B. M. L. C. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00275 · Cited by 293 · see citing works
Bianco, A. C., Anderson, G., Forrest, D., Galton, V. A., Gereben, B., Kim, B. W., Kopp, P. A., Liao, X. H., Obregon, M. J., Peeters, R. P., et al. (2014) · Thyroid · doi:10.1089/thy.2013.0109 · Cited by 205 · see citing works
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Fliers, E., & Boelen, A. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01482-4 · Cited by 199 · see citing works
Self-citationThe classic pathways of thyroid hormone metabolism
van der Spek, A. H., Fliers, E., & Boelen, A. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.025 · Cited by 194 · see citing works
The molecular basis of the non-thyroidal illness syndrome
de Vries, E. M., Fliers, E., & Boelen, A. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0133 · Cited by 192 · see citing works
Self-citationMECHANISMS IN ENDOCRINOLOGY: Beyond the fixed setpoint of the hypothalamus–pituitary–thyroid axis
Fliers, E., Kalsbeek, A., & Boelen, A. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0285 · Cited by 124 · see citing works
Self-citationLangouche, L., Vander Perre, S., Marques, M., Boelen, A., Wouters, P. J., Casaer, M. P., & Van den Berghe, G. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2809 · Cited by 79 · see citing works
Self-citationCoupling between Nutrient Availability and Thyroid Hormone Activation
Lartey, L. J., Werneck-de-Castro, J. P., O-Sullivan, I., Unterman, T. G., & Bianco, A. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665505 · Cited by 41 · see citing works
Differential effects of fasting vs food restriction on liver thyroid hormone metabolism in male rats
de Vries, E. M., van Beeren, H. C., Ackermans, M. T., Kalsbeek, A., Fliers, E., & Boelen, A. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0533 · Cited by 38 · see citing works
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Boelen, A., van der Spek, A. H., Bloise, F., de Vries, E. M., Surovtseva, O. V., van Beeren, M., Ackermans, M. T., Kwakkel, J., & Fliers, E. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0483 · Cited by 35 · see citing works
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- Authors
- Boelen, A., van Beeren, M., Vos, X., Surovtseva, O., Belegri, E., Saaltink, D.-J., Vreugdenhil, E., Kalsbeek, A., Kwakkel, J., & Fliers, E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Leiden University (NL)
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Boelen, Anita
- ORCID
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2012-02
- Volume
- 22
- Issue
- 2
- Pages
- 192-199
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2038918100
- Cited by
- 35
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 7 · 2016: 1 · 2015: 2 · 2014: 7 · 2013: 5
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Universiteit van Amsterdam
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- leptin, fasting, thyroid hormone metabolism, thyroid hormone receptor beta 1, thyroid hormone receptor alpha, type I deiodinase, hypothalamic-pituitary-thyroid axis, starvation, hepatic gene expression
- MeSH terms
- Animals, Fasting, Iodide Peroxidase, Liver, Thyroid Gland, Thyroxine, Triiodothyronine, Up-Regulation, Leptin, Thyroid Hormone Receptors alpha, Thyroid Hormone Receptors beta, Mice
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