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Thyroid Hormone Regulation of Metabolism
Open accessAbstract
Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T 4 ), to the active form, triiodothyronine (T 3 ), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.
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“LT4 suppression therapy may also affect metabolic function, since thyroid hormone plays a critical role in determining energy expenditure, body mass, and body composition (2).”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [2]
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“For example, thyroid hormones T4 and its active form, T3, as well as type 2 deiodinase (D2), an essential enzyme activating T4 to T3, are required for adaptive thermogenesis in BAT (de Jesus et al , 2001; Mullur et al , 2014).”
Metadata
- Authors
- Mullur, R., Liu, Y.-Y., & Brent, G. A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Brent, Gregory A.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2014-04
- Volume
- 94
- Issue
- 2
- Pages
- 355-382
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- PMC
- PMC4044302
- OpenAlex
- W1966824338
- Cited by
- 2,421
- References
- 292
- Citations by year
- 2026: 223 · 2025: 273 · 2024: 300 · 2023: 273 · 2022: 269 · 2021: 237 · 2020: 254 · 2019: 163 · 2018: 132 · 2017: 118 · 2016: 90 · 2015: 60 · 2014: 27
- FWCI
- 15.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (F32CA090073)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK98576, R01DK098576)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- thyroid hormones, thyroid hormone receptor, triiodothyronine, adaptive thermogenesis, brown adipose tissue, hypothalamus, thyrotropin-releasing hormone, thyroid-stimulating hormone, leptin, appetite regulation, adrenergic system, peroxisome proliferator-activated receptors, liver X receptor, bile acid signaling, hepatic insulin sensitivity, hepatic gluconeogenesis, cholesterol metabolism, carbohydrate metabolism, metabolic disorders
- MeSH terms
- Animals, Body Weight, Cholesterol, Energy Metabolism, Humans, Thyroid Gland, Thyroid Hormones, Triglycerides, Signal Transduction, Thermogenesis, Carbohydrate Metabolism
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