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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 […]

27.03.2011 | 2:27 PM

Crossing the Hurdles of Thyroid Hormone Receptor – Activation.

Thyroid hormone acts in virtually every biological sys- tem in vertebrates by controlling the expression of dif- ferent sets of genes. To achieve this, thyroid hormone inter- acts with two receptors (TR), TR and TR , located in the nucleus of its target cells, which turn gene transcription on or off and thus mediate the […]

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 […]

18.02.2011 | 10:50 PM

D2KO causes obesity, glucose intolerance and liver steatosis. PMID: 21335378

OBJECTIVE: Thyroid hormone accelerates energy expenditure; 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 […]

06.10.2010 | 1:31 PM

Inhibition of the Type 2 Iodothyronine Deiodinase Underlies the Elevated Plasma TSH Associated with Amiodarone Treatment. PMID: 20926587

The widely prescribed cardiac antiarrhythmic drug amiodarone (AMIO) and its main metabolite, desethylamiodarone (DEA), have multiple side effects on thyroid economy, including an elevation in serum TSH levels. To study the AMIO effect on TSH, mice with targeted disruption of the type 2 deiodinase gene (D2KO) were treated with 80 mg/kg AMIO for 4 wk. […]

09.09.2010 | 1:17 PM

Absence of Thyroid Hormone Activation during Development Underlies a Permanent Defect in Adaptive Thermogenesis.

Type 2 deiodinase (D2), which is highly expressed in brown adipose tissue (BAT), is an enzyme that amplifies thyroid hormone signaling in individual cells. Mice with inactivation of the D2 pathway (D2KO) exhibit dramatically impaired thermogenesis in BAT, leading to hypothermia during cold exposure and a greater susceptibility to diet-induced obesity. This was interpreted as […]

09.06.2010 | 1:56 PM

Paracrine signaling by glial cell–derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells.

Hypothyroidism in humans is characterized by severe neurological consequences that are often irreversible, highlighting the critical role of thyroid hormone (TH) in the brain. Despite this, not much is known about the signaling pathways that control TH action in the brain. What is known is that the prohormone thyroxine (T4) is converted to the active […]

09.06.2010 | 1:48 PM

Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway.

Thyroid hormone receptor (TR) and liver X-receptor (LXR) are the master regulators of lipid metabolism. Remarkably, a mouse with a targeted deletion of both LXRa and LXRb is resistant to western diet-induced obesity, and exhibits ectopic liver expression of the thyroid hormone activating type 2 deiodinase (D2). We hypothesized that LXR/retinoid X-receptor (RXR) signaling inhibits […]

09.06.2010 | 1:36 PM

Impaired Metabolic Effects of a Thyroid Hormone Receptor Beta-Selective Agonist in a Mouse Model of Diet-Induced Obesity.

Background: The use of selective agonists of the thyroid hormone receptor isoform b (TRb) has been linked to metabolic improvement in animal models of diet-induced obesity, nonalcoholic liver disease, and genetic hy- percholesterolemia. Methods: To identify potential target tissues of such compounds, we exposed primary murine brown adipocytes and skeletal myocytes for 24 hours to […]