Regulation of type 3 deiodinase in rodent liver and adipose tissue during fasting
| Autor: | Hermina C. van Beeren, Albert C.W.A. van Wijk, Anita Boelen, Andries Kalsbeek, Emmely M de Vries, Eric Fliers, Johannes A. Romijn |
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| Přispěvatelé: | Endocrinology, Endocrinology Laboratory, ANS - Cellular & Molecular Mechanisms, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Netherlands Institute for Neuroscience (NIN) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty fasting Endocrinology Diabetes and Metabolism Deiodinase Adipose tissue type 3 deiodinase 030209 endocrinology & metabolism Stimulation White adipose tissue liver lcsh:Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences 0302 clinical medicine Endocrinology white adipose tissue Downregulation and upregulation Internal medicine Constitutive androstane receptor Internal Medicine medicine PI3K/AKT/mTOR pathway lcsh:RC648-665 biology business.industry Research 030104 developmental biology biology.protein business Hormone |
| Zdroj: | Endocrine connections, 9(6), 552-562. BioScientifica Ltd. Endocrine Connections, Vol 9, Iss 6, Pp 552-562 (2020) Endocrine Connections Endocrine connections, 9, 552-562. BioScientifica Ltd. |
| ISSN: | 2049-3614 |
| Popis: | Fasting induces profound changes in the hypothalamus-pituitary-thyroid axis and peripheral thyroid hormone (TH) metabolism, ultimately leading to lower serum thyroid hormone (TH) concentrations. In the present study, we aimed to investigate the regulation of type 3 deiodinase (D3) during fasting in two metabolic tissues: liver and white adipose tissue (WAT). To this end, we studied the effect of modulation of the mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1α (HIF1α) on D3 expression in primary rat hepatocytes and in 3T3-L1 adipocytes. In addition, we studied the role of the constitutive androstane receptor (CAR) on liver TH metabolism using primary hepatocytes and CAR-/- mice. Twenty-four-hour fasting increased liver Dio3 expression in mice. Inhibition of mTOR using mTOR inhibitors markedly induced Dio3 mRNA expression in primary hepatocytes; this increase was accompanied by a small increase in D3 activity. Stimulation of these cells with a CAR agonist induced both Dio3 mRNA expression and activity. Fasting increased hepatic D3 expression in WT but not in CAR-/- mice. In WAT, Dio3 mRNA expression increased five-fold after 48-h fasting. Treatment of 3T3-L1 adipocytes with mTOR inhibitors induced Dio3 mRNA expression, whereas stimulation of these cells with cobalt chloride, a compound that mimics hypoxia and stabilizes HIF1α, did not induce Dio3 mRNA expression. In conclusion, our results indicate an important role of mTOR in the upregulation of D3 in WAT and liver during fasting. Furthermore, CAR plays a role in the fasting induced D3 increase in the liver. |
| Databáze: | OpenAIRE |
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