Levothyroxine treatment and cholesterol in hypothyroidism

Thyroid status and serum cholesterol levels are intimately linked. Hypothyroidism causes hypercholesterolaemia, which is thought to be resolved after treatment with levothyroxine and normalization of thyroid-stimulating hormone. However, some studies indicate that hypercholesterolaemia persists despite treatment, requiring more frequent use of statins

Thyroid Hormone Deiodinases and Cancer

Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches

Thyroid Hormone and the Neuroglia: Both Source and Target

Thyroid hormone plays a crucial role in the development and function of the nervous system. In order to bind to its nuclear receptor and regulate gene transcription thyroxine needs to be activated in the brain. This activation occurs via conversion of thyroxine to T3, which is catalyzed by the type 2 iodothyronine deiodinase (D2) in glial cells, in astrocytes, and tanycytes in the mediobasal hypothalamus. We discuss how thyroid hormone affects glial cell function followed by an overview on the fine-tuned regulation of T3 generation by D2 in different glial subtypes. Recent evidence on the direct paracrine impact of glial D2 on neuronal gene expression underlines the importance of glial-neuronal interaction in thyroid hormone regulation as a major regulatory pathway in the brain in health and disease

Scope and limitations of iodothyronine deiodinases in hypothyroidism.

The coordinated expression and activity of the iodothyronine deiodinases regulate thyroid hormone levels in hypothyroidism. Once heralded as the pathway underpinning adequate thyroid-hormone replacement therapy with levothyroxine, the role of these enzymes has come into question as they have been implicated in both an inability to normalize serum levels of tri-iodothyronine (T3) and the incomplete resolution of hypothyroid symptoms. These observations, some of which were validated in animal models of levothyroxine monotherapy, challenge the paradigm that tissue levels of T3 and thyroid-hormone signalling can be fully restored by administration of levothyroxine alone. The low serum levels of T3 observed among patients receiving levothyroxine monotherapy occur as a consequence of type 2 iodothyronine deiodinase (DIO2) in the hypothalamus being fairly insensitive to ubiquitination. In addition, residual symptoms of hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that might be a risk factor for neurodegenerative disease. Here, we discuss how these novel findings underscore the clinical importance of iodothyronine deiodinases in hypothyroidism and how an improved understanding of these enzymes might translate to therapeutic advances in the care of millions of patients with this condition

Effects of different circuit training protocols on body mass, fat mass and blood parameters among overweight adults

The benefits of regular exercise are known for a long time, but the mechanisms underlying the exercise mode recommendations for specific chronic cardiovascular diseases remains unclear. The aim of this study was to evaluate and compare the effects of different circuit training protocols in sedentary overweight adults

INFLUENCE OF FELDENKRAIS METHOD ON SPINE HEALTH IN PROFESSIONAL ORCHESTRAL MUSICIANS. PILOT STUDY/INFLUENZA DEL METODO FELDENKRAIS SULLA SALUTE DEL RACHIDE IN MUSICISTI ORCHESTRALI PROFESSIONISTI. STUDIO PILOTA

Obiettivo: Lo scopo di questo studio è stato quello di esaminare se il Metodo Feldenkrais fosse utile per migliorare la flessibilità muscolare e ridurre il dolore alla schiena in musicisti orchestrali professionisti. Materiali e metodi: Diciassette partecipanti sono stati reclutati da un orchestra sinfonica di Palermo (Italia) e divisi casualmente in un gruppo di controllo (C, n = 8) e un gruppo Feldenkrais (F, n = 9). Il primo non ha partecipato al protocollo Feldenkrais e a qualsiasi altra attività fisica; mentre il secondo ha preso parte ad un programma costituito da quattro lezioni di gruppo di Consapevolezza Attraverso il Movimento (CAM) eseguito 2 ore alla settimana per 4 settimane. Al fine di valutare lo stato di salute della colonna vertebrale, abbiamo usato il sit-and-reach test ed il trunk lift test. Le differenze all'interno di ogni gruppo e tra il gruppo C e il gruppo F sono state rispettivamente esaminate con il test di Wilcoxon e quello di Mann-Whitney; e considerate significative con p ≤ 0,05. Risultati: La flessibilità muscolare del bicipite femorale e della regione lombare, e la forza, la flessibilità e la resistenza dei muscoli estensori del tronco era leggermente aumentata nel gruppo F rispetto al gruppo C dopo il protocollo Feldenkrais; anche se questa variazione non era statisticamente significativa. Diversamente, il gruppo C ha mostrato una riduzione del 5% in entrambi i test dopo 4 settimane. Dopo il protocollo Feldenkrais, l’altezza del gruppo F era significativamente maggiore rispetto a prima del trattamento. Inoltre, abbiamo trovato che il numero dei partecipanti, che hanno dichiarato di avere dolore forte e frequente alla schiena e agli arti, diminuiva durante il periodo di svolgimento del protocollo Feldenkrais. Questo effetto era maggiore nella regione cervicale rispetto a quella lombare e agli arti superiori. Conclusioni: I nostri risultati mostrano che il Metodo Feldenkrais ha effetti positivi sulla flessibilità muscolare e supporta l'uso di questo metodo per sciogliere le tensioni e le contrazioni muscolari che possono causare dolore nei musicisti orchestrali professionisti.Objectives: The aim of this study was to explore whether Feldenkrais Method was useful for improving muscular flexibility and reducing back pain in professional orchestral musicians. Materials and methods: Seventeen participants were recruited from a symphony orchestra of Palermo (Italy) and randomly divided in a control group (C, n=8) and a Feldenkrais group (F, n=9). The first didn’t participate in the Feldenkrais protocol and any other physical activity; while the second took part into a program consisting of four Awareness through movement (ATM) classes performed 2 hours/week for 4 weeks. In order to assess muscle fitness of spine, we used sit-and-reach and trunk lift test. The differences within each group and between C and F groups were respectively examined with Wilcoxon matched pair test and Mann-Whitney test; and considered significant with p≤0.05. Results: The muscular flexibility of hamstring and low back, and trunk extensor strength, flexibility and endurance slightly increased in F group compared with C group after Feldenkrais protocol even if this variation was not statistically significant. Differently, C group showed a reduction by 5% in both tests after 4 weeks. After Feldenkrais protocol, height of F group was significantly bigger than before treatment. Moreover, we found that the number of participants, who stated to have strong and frequent pain in the back and limbs, decreased during performing the Feldenkrais protocol. This effect was bigger in the cervical than lumbar spine and upper limbs.Conclusion: Our outcomes illustrate that Feldenkrais method has positive effects on muscle flexibility and supports the use of this method for dissolving muscle tensions and contractions that can cause pain in professional orchestral musicians

Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

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 thermogenesis). 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 the role of perilipin PKA phosphorylation in BAT NE-stimulated thermogenesis using a novel mouse model in which a mutant form of perilipin, lacking all six PKA phosphorylation sites, is expressed in adipocytes of perilipin knockout (Peri KO) mice. Here, we show that despite a normal mitochondrial respiratory capacity, NE-induced lipolysis is abrogated in the interscapular brown adipose tissue (IBAT) of these mice. This lipolytic constraint is accompanied by a dramatic blunting (∼70%) of the in vivo thermal response to NE. Thus, in the presence of perilipin, PKA-mediated perilipin phosphorylation is essential for NE-dependent lipolysis and full adaptive thermogenesis in BAT. In IBAT of Peri KO mice, increased basal lipolysis attributable to the absence of perilipin is sufficient to support a rapid NE-stimulated temperature increase (∼3.0°C) comparable to that in wild-type mice. This observation suggests that one or more NE-dependent mechanism downstream of perilipin phosphorylation is required to initiate and/or sustain the IBAT thermal response

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

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 whether the impaired thermogenesis of D2KO mice increases their susceptibility to obesity when placed on a high-fat diet. Research Design and Methods: To test this, D2KO mice were admitted to a comprehensive monitoring system acclimatized to room temperature (22$^\circ$C) or thermoneutrality (30$^\circ$C) and kept either on chow or high-fat diet for 60 days. Results: At 22$^\circ$C, D2KO mice preferentially oxidize fat, have a similar sensitivity to diet-induced obesity, and are supertolerant to glucose. However, when thermal stress is eliminated at thermoneutrality (30$^\circ$C), an opposite phenotype is encountered, one that includes obesity, glucose intolerance, and exacerbated hepatic steatosis. We suggest that a compensatory increase in BAT sympathetic activation of the D2KO mice masks metabolic repercussions that they would otherwise exhibit. Conclusions: Thus, upon minimization of thermal stress, high-fat feeding reveals the defective capacity of D2KO mice for diet-induced thermogenesis, provoking a paradigm shift in the understanding of the role of the thyroid hormone in metabolism