Cited by 174Mitochondrial Function and PathologyAdipose Tissue and MetabolismThyroid Disorders and Treatments

Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle

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Lebon, Vincent, Dufour, Sylvie, Petersen, Kitt Falk, Ren, Jianming, Jucker, Beat M., Slezak, Lori A., Cline, Gary W., Rothman, Douglas L. +1 more·2001·Journal of Clinical Investigation

Abstract

The mechanism underlying the regulation of basal metabolic rate by thyroid hormone remains unclear. Although it has been suggested that thyroid hormone might uncouple substrate oxidation from ATP synthesis, there are no data from studies on humans to support this hypothesis. To examine this possibility, we used a novel combined 13C/31P nuclear magnetic resonance (NMR) approach to assess mitochondrial energy coupling in skeletal muscle of seven healthy adults before and after three days of triiodothyronine (T3) treatment. Rates of ATP synthesis and tricarboxylic acid (TCA) cycle fluxes were measured by 31P and 13C NMR spectroscopy, respectively, and mitochondrial energy coupling was assessed as the ratio. Muscle TCA cycle flux increased by approximately 70% following T3 treatment. In contrast, the rate of ATP synthesis remained unchanged. Given the disproportionate increase in TCA cycle flux compared with ATP synthesis, these data suggest that T3 promotes increased thermogenesis in part by promoting mitochondrial energy uncoupling in skeletal muscle.

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  • 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.”
  • 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.”
  • 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).”

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Research works printed but not linked: 2

  1. Mason, G.F. 2000. CWave: software for the design and analysis of 13 C labeling studies performed in vivo. Proc. Intl. Soc. Mag. Reson. Med. 3:1870 (Abstr.)
  2. Field, J., Beldings, H.S., and Martin, A.W. 1939. An analysis of the rela- tion between basal metabolism and summated tissue respiration in the rat. Journal of Cellular and Comparative Physiology. 14:143-157.

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Authors
Lebon, V., Dufour, S., Petersen, K. F., Ren, J., Jucker, B. M., Slezak, L. A., Cline, G. W., Rothman, D. L., & Shulman, G. I.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Yale University (US)
  • Bristol-Myers Squibb (United States) (US)
Corresponding author
Shulman, Gerald I.
Venue
Journal of Clinical Investigation
Published
2001-09-01
Volume
108
Issue
5
Pages
733-737
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2141034558
Cited by
174
References
36
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 3 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 11 · 2015: 8 · 2014: 4 · 2013: 8 · 2012: 9
FWCI
3.27
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Yale University
  • U.S. Public Health Service (P30 DK45735, R01 DK-49230)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, R01DK049230, R01 DK-49230, P30DK045735)
  • National Center for Research Resources (M01RR000125, M01 RR-00125)
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, thyroid hormones, uncoupling, skeletal muscle, basal metabolic rate, thermogenesis, ATP production, TCA cycle flux, substrate oxidation
MeSH terms
Adenosine Triphosphate, Adult, Citric Acid Cycle, Female, Humans, Male, Mitochondria, Magnetic Resonance Spectroscopy, Oxidative Phosphorylation, Triiodothyronine, Muscle, Skeletal, Glutamic Acid

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