ArticleProceedings of the National Academy of Sciences of the United States of America2020
The paradoxical lean phenotype of hypothyroid mice is marked by increased adaptive thermogenesis in the skeletal muscle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Relationship between Prenatal or Postnatal Exposure to Pesticides and Obesity: A Systematic Review.International journal of environmental research and public health · 2021Pooled it
- Concomitant Effect of Hypothyroidism with Obesity on Testicular and Sperm Function in Male ICR Mice: Involvement of TGFβ/SMAD Signaling.Cell biochemistry and biophysics · 2026Article
- Exploring the effects of high protein versus high fat snacks on satiety, gut hormones and insulin secretion in women with overweight and obesity: A randomized clinical trial.Obesity pillars · 2025Article
- Methionine Supplementation Benefits Lipogenesis in Goat Intramuscular Adipocytes, Likely by Inhibiting the Expression ofAnimals : an open access journal from MDPI · 2025Article
- Site-1 protease is a negative regulator of sarcolipin promoter activity.Communications biology · 2025Article
- Causal associations between thyroid function and sarcopenia-related traits: a Mendelian randomization study.Hormones (Athens, Greece) · 2025Article
- Systemic inhibition ofbioRxiv : the preprint server for biology · 2024Article
- Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice.Scientific reports · 2024Article
- Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis.Nature metabolism · 2023Article
- Article
- Hypermetabolism in mice carrying a near complete human chromosome 21.bioRxiv : the preprint server for biology · 2023Article
- Low Bone Turnover Due to Hypothyroidism or Anti-Resorptive Treatment Does Not Affect Whole-Body Glucose Homeostasis in Male Mice.Journal of personalized medicine · 2022Article
- Article
- The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis.Metabolites · 2022Review
- Whole-body endothermy: ancient, homologous and widespread among the ancestors of mammals, birds and crocodylians.Biological reviews of the Cambridge Philosophical Society · 2022Article
- Thyroid hormones in the regulation of brown adipose tissue thermogenesis.Endocrine connections · 2021Review
- Strain-specific differences in muscle CaThe Journal of experimental biology · 2021Article
- Is Upregulation of Sarcolipin Beneficial or Detrimental to Muscle Function?Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity is a major health problem worldwide, given its growing incidence and its association with a variety of comorbidities. Weight gain results from an increase in energy intake without a concomitant increase in energy expenditure. To combat the obesity epidemic, many studies have focused on the pathways underlying satiety and hunger signaling, while other studies have concentrated on the mechanisms involved in energy expenditure, most notably adaptive thermogenesis. Hypothyroidism in humans is typically associated with a decreased basal metabolic rate, lower energy expenditure, and weight gain. However, hypothyroid mouse models have been reported to have a leaner phenotype than euthyroid controls. To elucidate the mechanism underlying this phenomenon, we used a drug-free mouse model of hypothyroidism: mice lacking the sodium/iodide symporter (NIS), the plasma membrane protein that mediates active iodide uptake in the thyroid. In addition to being leaner than euthyroid mice, owing in part to reduced food intake, these hypothyroid mice show signs of compensatory up-regulation of the skeletal-muscle adaptive thermogenic marker sarcolipin, with an associated increase in fatty acid oxidation (FAO). Neither catecholamines nor thyroid-stimulating hormone (TSH) are responsible for sarcolipin expression or FAO stimulation; rather, thyroid hormones are likely to negatively regulate both processes in skeletal muscle. Our findings indicate that hypothyroidism in mice results in a variety of metabolic changes, which collectively lead to a leaner phenotype. A deeper understanding of these changes may make it possible to develop new strategies against obesity.
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