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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 […]

09.04.2011 | 11:49 AM

Disruption of Thyroid Hormone Activation in Type 2 Deiodinase Knockout Mice Causes Obesity With Glucose Intolerance and Liver Steatosis Only at Thermoneutrality.

Thyroid hormone accelerates energy expendi- ture; thus, hypothyroidism is intuitively associated with obesity. However, studies failed to establish such a connection. In brown adipose tissue (BAT), thyroid hormone activation via type 2 deiodinase (D2) is necessary for adaptive thermogenesis, such that mice lacking D2 (D2KO) exhibit an impaired thermogenic response to cold. Here we investigate […]

01.04.2011 | 12:00 AM

Responsiveness to Thyroid Hormone and to Ambient Temperature Underlies Differences Between Brown Adipose Tissue and Skeletal Muscle Thermogenesis in a Mouse Model of Diet-Induced Obesity.

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

27.02.2011 | 2:46 PM

The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure.

Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deio- dinase (D2) to the chemical chaperones tauroursodeoxycholic acid (TUDCA) or 4-phenylbutiric acid (4-PBA) increases D2 expression, activity and T3 production. In brown adipocytes, TUDCA or 4-PBA induced T3-dependent genes and oxygen consumption ( 2-fold), an effect partially lost in D2 knockout […]