3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?
Abstract
:1. Introduction
1.1. Initial Decades of Promising 3,5-T2 Research
1.2. Discovery of 3,5-T2 in the Serum and Subsequent Research
2. Direct Mitochondrial Actions of 3,5-T2
3. Mechanisms Postulated for 3,5-T2 Actions
4. Effects of 3,5-T2 in Tissues of the HPT Axis
4.1. 3,5-T2 and the Pituitary
4.2. 3,5-T2 Effects May Depend on the Thyroid State
5. Hepatic Effects of 3,5-T2
5.1. Canonical 3,5-T2 Actions in the Liver of Rodents
5.2. Noncanonical 3,5-T2 Actions in the Liver of Rodents
5.3. Lipid Metabolism
5.4. Thyromimetic Effects of 3,5-T2 on Glucose Metabolism
5.5. Hepatic Accumulation, Selective Uptake and Inefficient Hepatic Elimination of 3,5-T2
5.6. Implications of High 3,5-T2 in Context of Low T3, T4, and Suppressed TSH for Hepatic Lipid Metabolism
5.7. Hepatic 3,5-T2 Effects Differ between Lean and HFD Obese Mice
6. 3,5-T2 and the Heart
7. Dose Issues of 3,5-T2
8. Limitations, Deficits, Problem Areas and Challenges in 3,5-T2 Research
9. Clinical Potential
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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1 | C | 3,5-T2 |
---|---|---|
Hepatic CS activity (µmol·min−1·min−1) | 700 ± 30.0 | 1024 ± 35.7 ** |
Hepatic D1 activity (pmol·mg−1·min−1) | 150 ± 52 | 380 ± 93 *** |
Serum triglycerides (µg/mL) | 80 ± 7.3 | 97 ± 12.1 |
Free fatty acids (mM) | 0.65 ± 0.04 | 0.68 ± 0.04 |
Total cholesterol (mg/dL) | 181 ± 7.1 | 104 ± 8.0 *** |
Liver triglycerides (µg/g protein) | 1.18 ± 0.39 | 0.73 ± 0.13 * |
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Sane, R.; Wirth, E.K.; Köhrle, J. 3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development? Metabolites 2022, 12, 582. https://doi.org/10.3390/metabo12070582
Sane R, Wirth EK, Köhrle J. 3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development? Metabolites. 2022; 12(7):582. https://doi.org/10.3390/metabo12070582
Chicago/Turabian StyleSane, Rajas, Eva K. Wirth, and Josef Köhrle. 2022. "3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?" Metabolites 12, no. 7: 582. https://doi.org/10.3390/metabo12070582