Differential effects of fasting vs food restriction on liver thyroid hormone metabolism in male rats
Open accessAbstract
A variety of illnesses that leads to profound changes in the hypothalamus–pituitary–thyroid (HPT) are axis collectively known as the nonthyroidal illness syndrome (NTIS). NTIS is characterized by decreased tri-iodothyronine (T 3 ) and thyroxine (T 4 ) and inappropriately low TSH serum concentrations, as well as altered hepatic thyroid hormone (TH) metabolism. Spontaneous caloric restriction often occurs during illness and may contribute to NTIS, but it is currently unknown to what extent. The role of diminished food intake is often studied using experimental fasting models, but partial food restriction might be a more physiologically relevant model. In this comparative study, we characterized hepatic TH metabolism in two models for caloric restriction: 36 h of complete fasting and 21 days of 50% food restriction. Both fasting and food restriction decreased serum T 4 concentration, while after 36-h fasting serum T 3 also decreased. Fasting decreased hepatic T 3 but not T 4 concentrations, while food restriction decreased both hepatic T 3 and T 4 concentrations. Fasting and food restriction both induced an upregulation of liver D3 expression and activity, D1 was not affected. A differential effect was seen in Mct10 mRNA expression, which was upregulated in the fasted rats but not in food-restricted rats. Other metabolic pathways of TH, such as sulfation and UDP-glucuronidation, were also differentially affected. The changes in hepatic TH concentrations were reflected by the expression of T 3 -responsive genes Fas and Spot14 only in the 36-h fasted rats. In conclusion, limited food intake induced marked changes in hepatic TH metabolism, which are likely to contribute to the changes observed during NTIS.
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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 [24]
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Thyroid-Liver Axis: Mechanistic Insights and Clinical Implications
Parveen, N., Chittawar, S., Khandelwal, D., & Aggarwal, S. (2026) · Cureus · doi:10.7759/cureus.110637
- Authors
- de Vries, E. M., van Beeren, H. C., Ackermans, M. T., Kalsbeek, A., Fliers, E., & Boelen, A.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2014-10-27
- Volume
- 224
- Issue
- 1
- Pages
- 25-35
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2326301984
- Cited by
- 38
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 2
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- low T3 syndrome, fasting, dietary restriction, caloric restriction, triiodothyronine, thyroxine, type 3 deiodinase, MCT10, Fas, hypothalamic-pituitary-thyroid axis
- MeSH terms
- Animals, Body Weight, Eating, Euthyroid Sick Syndromes, Fasting, Food Deprivation, Iodide Peroxidase, Liver, Male, Thyroid Hormones, Rats, Wistar, Amino Acid Transport Systems, Neutral, Caloric Restriction, Rats
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