ARCHIVE

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 […]

27.05.2010 | 1:53 PM

New insights into thyroid hormone replacement therapy.

It is widely accepted that thyroid hormone replacement for patients with hypothyroidism can be fully accomplished with levothyroxine monotherapy, as assessed by serum thyroid function tests. However, approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine monotherapy, and physicians continue to report benefits from combined levothyroxine-triidothyronine therapy for some hypothyroid patients. Recently, […]

09.01.2010 | 1:44 PM

Expression of Uncoupling Protein 1 in Mouse Brown Adipose Tissue Is Thyroid Hormone Receptor- Isoform Specific and Required for Adaptive Thermogenesis.

Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT). BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T3, and uncoupling protein 1 (UCP1) expression. Our previous studies with a thyroid hormone receptor- (TR ) […]

09.11.2009 | 10:31 AM

Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences.

The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting the ex- pression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control thyroid hormone action by acti- vating or inactivating the precursor molecule thyro- xine that is secreted by the […]

17.09.2009 | 9:39 AM

Thyroid Hormone-Related Regulation of Gene Expression in Human Fatty Liver.

Context: Fatty liver is an important complication of obesity; however, regulatory mechanisms mediating altered gene expression patterns have not been identified. Objective: The aim of the study was to identify novel transcriptional changes in human liver that could contribute to hepatic lipid accumulation and associated insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis. Design: We […]