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13.04.2007 | 11:40 AM

Ubiquitination-Induced Conformational Change within the Deiodinase Dimer Is a Switch Regulating Enzyme Activity.

Ubiquitination is a critical posttranslational regulator of protein stability and/or subcellular localization. Here we show that ubiquitination can also regulate proteins by transiently inactivating enzymatic function through conformational change in a dimeric enzyme, which can be reversed upon deubiquitination. Our model system is the thyroid hormone-activating type 2 deiodinase (D2), an endoplasmic reticulum-resident type 1 […]

06.04.2007 | 9:30 AM

Peroxisome Proliferator Activator Receptor Coactivator-1 Expression Is Reduced in Obesity.

Peroxisome proliferator activator receptor- coactivator 1 (PGC-1) is a major candidate gene for diabetes-related meta- bolic phenotypes, contributing to decreased expression of nuclear-encoded mitochondrial genes in muscle and adipose tissue. We have demonstrated that muscle expression of PGC-1 and – is reduced in both genetic (Lepob/Lepob) and acquired obesity (high fat diet). In C57BL6 mice, […]

30.03.2007 | 11:53 AM

Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue.

Abstract In response to cold, norepinephrine (NE)- induced triacylglycerol hydrolysis (lipolysis) in adipocytes of brown adipose tissue (BAT) provides fatty acid substrates to mitochondria for heat generation (adaptive thermogen- esis). NE-induced lipolysis is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin, a lipid droplet-associated protein that is the major regulator of lipolysis. We investigated […]

23.03.2007 | 9:36 AM

The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone Activation.

Disturbances in energy homeostasis can result in obesity and other metabolic diseases. Here we report a metabolic pathway present in normal human skeletal muscle myo- blasts that is activated by the small polyphenolic molecule kaempferol (KPF). Treatment with KPF leads to an 30% increase in skeletal myocyte oxygen consumption. The mech- anism involves a several-fold […]

23.02.2007 | 9:48 AM

Thyroid hormone receptor b-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats.

It is well known that thyroid hormone affects body composition; however, the effect of the thyroid hormone receptor b (TRb)- selective thyromimetic GC-1 on this biological feature had not been demonstrated. In the current study, we compared the effects of a 6-week treatment with triiodothyronine (T3; daily injections of 3 or 6 mg/100 g body […]

30.11.2006 | 9:42 AM

Mice with Impaired Extrathyroidal Thyroxine to 3,5,3 – Triiodothyronine Conversion Maintain Normal Serum 3,5,3 -Triiodothyronine Concentrations.

For T3 to mediate its biological effects, the prohormone T4 must be activated by removal of an outer-ring iodine by the type 1 or 2 deiodinases (D1 and D2) with approximately 60% of the daily T3 production in rodents being produced extra- thyroidally through this pathway. To further define the role of these enzymes in […]

20.10.2006 | 10:01 AM

Metabolic Instability of Type 2 Deiodinase Is Transferable To Stable Proteins Independently of Subcellular Localization.

The deiodinases activate or inactivate thyroid hormone, and their importance in thyroid hormone homeostasis has become increasingly clear with the availability of deiodinase-deficient animals. At the same time, heightened interest in the field has been generated following the discovery that the type 2 deiodinase can be an important component in both the Hedgehog signaling pathway […]

09.06.2006 | 10:14 AM

Perilipin Promotes Hormone-sensitive Lipase-mediated Adipocyte Lipolysis via Phosphorylation-dependent and -independent Mechanisms.

Type 2 iodothyronine deiodinase (D2) activates T4 by deiodi- nation to T3, a process being the source of most T3 present in the brain. In the mediobasal hypothalamus, expression of the dio2 gene is potently activated by administration of bacterial lipopolysaccharide (LPS), which in turn mediates the modi- fications in thyroid homeostasis typically observed in […]

25.05.2006 | 10:07 AM

Characterization of the Nuclear Factor- B Responsiveness of the Human dio2 Gene.

Type 2 iodothyronine deiodinase (D2) activates T4 by deiodi- nation to T3, a process being the source of most T3 present in the brain. In the mediobasal hypothalamus, expression of the dio2 gene is potently activated by administration of bacterial lipopolysaccharide (LPS), which in turn mediates the modi- fications in thyroid homeostasis typically observed in […]

26.01.2006 | 10:27 AM

Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation.

While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase path- ways1,2, are ligands for the G-protein-coupled receptor (GPCR) TGR53,4 and activate nuclear hormone receptors such as farnesoid X […]