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21.09.2012 | 10:00 AM

Major role played by β1-adrenergic receptor in BAT. PMID: 22728333

Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple b-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the b1 isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) […]

20.06.2012 | 10:00 AM

Neuronal hypoxia induces nuclear import of D3. PMID: 22723689

D3 redirection and accumulation in the cell nucleus is part of the hypoxia-induced reduction in thyroid hormone signaling. Inactivation of thyroid hormone in the nucleus, physically closer to where thyroid hormone receptors (TRs) are located, constitutes an advantageous mechanism to dampen thyroid hormone signaling and reduce metabolism. Studies of directed D3 glycosylation indicated that D3 […]

18.06.2012 | 9:44 PM

Hypothalamic secretory systems are influenced by TH. PMID: 22719854

Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8)-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3)-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in […]

26.05.2012 | 10:00 AM

Inactivation of Dio3 in the heart causes fibrosis and LVH. PMID: 22403173

Cardiac injury induces myocardial expression of the thyroid hormone inactivating type 3 deiodinase (D3), which in turn dampens local thyroid hormone signaling. Here, we show that the D3 gene (Dio3) is a tissue-specific imprinted gene in the heart, and thus, heterozygous D3 knockout (HtzD3KO) mice constitute a model of cardiac D3 inactivation in an otherwise […]

25.12.2011 | 10:00 AM

ER stress decreases thyroid hormone activation. PMID: 22053000

Cells respond rapidly to endoplasmic reticulum (ER) stress by blocking protein translation, increasing protein folding capacity, and accelerating degradation of unfolded proteins via ubiquitination and ER-associated degradation pathways. The ER resident type 2 deiodinase (D2) is normally ubiquitinated and degraded in the proteasome, a pathway that is accelerated by enzyme catalysis of T4 to T3. […]

16.10.2011 | 11:17 PM

D3 is expressed in β-cells; regulates insulin secretion. PMID: 21828183

Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3′-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback […]

20.09.2011 | 10:23 AM

Endoplasmic Reticulum Stress Decreases Intracellular Thyroid Hormone Activation via an eIF2a-Mediated Decrease in Type 2 Deiodinase Synthesis. PMID: 22053000

Cells respond rapidly to endoplasmic reticulum (ER) stress by blocking protein translation, increas- ing protein folding capacity, and accelerating degradation of unfolded proteins via ubiquitina- tion and ER-associated degradation pathways. The ER resident type 2 deiodinase (D2) is normally ubiquitinated and degraded in the proteasome, a pathway that is accelerated by enzyme catalysis of T4 […]

16.09.2011 | 11:22 PM

T3-thermogenesis depends on ambient temperature. PMID: 21771890

Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroidhormonein the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but […]

27.05.2011 | 2:19 PM

The Thyroid Hormone-Inactivating Type III Deiodinase Is Expressed in Mouse and Human – Cells and Its Targeted Inactivation Impairs Insulin Secretion.

Cells are not passive bystanders in the process of hormonal signaling and instead can actively customize hormonal action. Thyroid hormone gains access to the intracellular environment via membrane transporters, and while diffusing from the plasma membrane to the nucleus, thyroid hormone signaling is modified via the action of the deiodinases. Although the type 2 deiodinase […]

28.04.2011 | 12:02 PM

Wnt signaling regulates mitochondrial physiology and insulin sensitivity.

Mitochondria serve a critical role in physiology and disease. The genetic basis of mitochondrial regulation in mammalian cells has not yet been detailed. We performed a large-scale RNAi screen to systematically identify genes that affect mitochondrial abundance and function. This screen revealed previously unrecognized roles for >150 proteins in mitochondrial regulation. We report that increased […]