Triiodothyronine‐mediated upregulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes
Abstract
Triiodothyronine (T3) increases mitochondrial respiration and promotes the uncoupling between oxygen consumption and ATP synthesis. T3 effect is mediated partly through transcriptional control of genes encoding mitochondrial proteins. We determined the effect of T3 on mRNA levels of uncoupling proteins (UCP) and proteins involved in the biogenesis of the respiratory chain in human skeletal muscle and on UCP2 mRNA expression in adipose tissue. Ten young, healthy males received 75 to 100 µg of T3 per day for 14 days. The increase in plasma‐free T3 levels was associated with an increase of resting metabolic rate and a decrease of respiratory quotient. In skeletal muscle, treatment with T3 induced a twofold increase of both UCP2 and UCP3 mRNA levels (p < 0.01). The mRNA levels of cytochrome c oxidase subunits 2 and 4, nuclear respiratory factor 1, mitochondrial transcription factor A, and the co‐activator PGC1 did not change during the treatment. In adipose tissue, UCP2 mRNA levels increased threefold. The direct effect of T3 on skeletal muscle and adipose tissue UCP2 and UCP3 mRNA expression was demonstrated in vitro in human primary cultures. Our data show that T3 induces UCP2 and UCP3 mRNA expression in humans. In skeletal muscle, UCP regulation by T3 is not associated with the transcriptional regulation of respiratory chain proteins.
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Most prior studies of supraphysiologic thyroid hormone doses utilized high doses of levotriiodothyronine (LT3), not minimally suppressive doses of LT4.
“In addition, most utilized high doses of levotriiodothyronine (LT3), not minimally suppressive doses of LT4.”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [4]
Short-term studies of supraphysiologic thyroid hormone doses uniformly showed increased resting and 24-hour energy expenditure, but were too brief to document changes in body composition.
“These studies uniformly showed increased resting and 24-hour energy expenditure, but were too brief to document changes in body composition.”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [4]
Past studies have reported increased resting or 24-hour energy expenditure and whole body oxygen consumption with exogenous administration of pharmacologic doses of LT4 or LT3 to healthy humans due to increased expression of uncoupling proteins and decreased mitochondrial efficiency.
“Past studies have reported increased resting or 24-hour energy expenditure and whole body oxygen consumption with exogenous administration of pharmacologic doses of LT4 or LT3 to healthy humans (3-7) due to increased expression of uncoupling proteins and decreased mitochondrial efficiency (3,4,7).”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [4]
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- Authors
- Barbe, P., Larrouy, D., Boulanger, C., Chevillotte, E., Viguerie, N., Thalamas, C., Oliva Trastoy, M., Roques, M., Vidal, H., & Langin, D.
- Affiliations
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Hôpital Purpan (FR)
- INSERM Unit 317 Institut Louis Bugnard Université Paul Sabatier Hôpital Rangueil Toulouse France
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2000-11-09
- Volume
- 15
- Issue
- 1
- Pages
- 13-15
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2159785275
- Cited by
- 118
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 7
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale (4P007E, 4P020D)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- triiodothyronine, uncoupling proteins, UCP2, UCP3, skeletal muscle, adipose tissue, mitochondrial uncoupling, mitochondrial transcription factors, PGC-1, resting metabolic rate, respiratory quotient
- MeSH terms
- Uncoupling Protein 2, Uncoupling Protein 3, Adipose Tissue, Carrier Proteins, Cells, Cultured, DNA, Mitochondrial, Electron Transport, Humans, Ion Channels, Male, Mitochondria, Models, Biological, Models, Genetic, Proteins, RNA, Messenger, Triiodothyronine, Uncoupling Agents, Up-Regulation, Muscle, Skeletal, Mitochondrial Proteins, Membrane Transport Proteins
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