Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity

<p>Abstract</p> <p>Background</p> <p>Obesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR) is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin), the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity.</p> <p>Methods</p> <p>In the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated.</p> <p>Results</p> <p>We here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6) by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (<it>P </it>< 0.05). Finally, the TSHR expression in adipose tissues was determined in 120 patients. The results showed that TSHR expression in subcutaneous adipose tissue is correlated with BMI (body mass index).</p> <p>Conclusion</p> <p>Taken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.</p

Associations of [18F]-APN-1607 Tau PET Binding in the Brain of Alzheimer's Disease Patients With Cognition and Glucose Metabolism.

Molecular imaging of tauopathies is complicated by the differing specificities and off-target binding properties of available radioligands for positron emission tomography (PET). [18F]-APN-1607 ([18F]-PM-PBB3) is a newly developed PET tracer with promising properties for tau imaging. We aimed to characterize the cerebral binding of [18F]-APN-1607 in Alzheimer's disease (AD) patients compared to normal control (NC) subjects. Therefore, we obtained static late frame PET recordings with [18F]-APN-1607 and [18F]-FDG in patients with a clinical diagnosis of AD group, along with an age-matched NC group ([18F]-APN-1607 only). Using statistical parametric mapping (SPM) and volume of interest (VOI) analyses of the reference region normalized standardized uptake value ratio maps, we then tested for group differences and relationships between both PET biomarkers, as well as their associations with clinical general cognition. In the AD group, [18F]-APN-1607 binding was elevated in widespread cortical regions (P < 0.001 for VOI analysis, familywise error-corrected P < 0.01 for SPM analysis). The regional uptake in AD patients correlated negatively with Mini-Mental State Examination score (frontal lobe: R = -0.632, P = 0.004; temporal lobe: R = -0.593, P = 0.008; parietal lobe: R = -0.552, P = 0.014; insula: R = -0.650, P = 0.003; cingulum: R = -0.665, P = 0.002) except occipital lobe (R = -0.417, P = 0.076). The hypometabolism to [18F]-FDG PET in AD patients also showed negative correlations with regional [18F]-APN-1607 binding in some signature areas of AD (temporal lobe: R = -0.530, P = 0.020; parietal lobe: R = -0.637, P = 0.003; occipital lobe: R = -0.567, P = 0.011). In conclusion, our results suggested that [18F]-APN-1607 PET sensitively detected tau deposition in AD and that individual tauopathy correlated with impaired cerebral glucose metabolism and cognitive function

SARS-related Virus Predating SARS Outbreak, Hong Kong

Using immunofluorescence and neutralization assays, we detected antibodies to human severe acute respiratory syndrome–associated coronavirus (SARS-CoV) and/or animal SARS-CoV–like virus in 17 (1.8%) of 938 adults recruited in 2001. This finding suggests that a small proportion of healthy persons in Hong Kong had been exposed to SARS-related viruses at least 2 years before the recent SARS outbreak

Ice-regenerated flame retardant and robust film of Bombyx mori silk fibroin and POSS nano-cages

In this study, we present a simple method to prepare and control the structure of regenerated hybrid silkworm silk films through icing. A regenerated hybrid silk (RHS) film consisting of a micro-fibrillar structure was obtained by partially dissolving amino-functionalized polyhedral oligomeric silsesquioxanes (POSS) and silk fibers in a CaCl(2)–formic acid solution. After immersion in water and icing, the obtained films of RHS showed polymorphic and strain-stiffening behaviors with mechanical properties that were better than those observed in dry or wet-regenerated silk. It was also found that POSS endowed the burning regenerated silk film with anti-dripping properties. The higher β-sheet content observed in the ice-regenerated hybrid micro-fibrils indicates a useful route to fabricate regenerated silk with physical and functional properties, i.e. strain-stiffening, similar to those observed to date in natural spider silk counterpart and synthetic rubbers, and anti-dripping of the flaming melt. Related carbon nanotube composites are considered for comparison

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Magnetic metal organic frameworks (MOFs) composite for removal of lead and malachite green in wastewater

We designed and synthesized a magnetic metal organic frameworks (MOFs) composite, Cu-MOFs/FeO as the adsorbent for removal of lead (Pb(II)) and malachite green (MG) in wastewater. This Cu-MOFs/FeO can be easily prepared by in-situ growth of Cu-MOFs with doping FeO nanoparticles. The prepared Cu-MOFs/FeO composite was well characterized by SEM, XRD, and FTIR spectra. The adsorption experiments found that Cu-MOFs/FeO can serve as adsorbent for removal of Pb(II) and MG simultaneously. The adsorption capacities were found to be 113.67 mg/g for MG and 219.00 mg/g for Pb, respectively, which are significantly higher than reported materials. Adsorption isotherm, kinetics and recyclability of Cu-MOFs/FeO for removal of Pb(II) and MG were then studied. Adsorption of Pb(II) and MG exhibited Freundlich adsorption isotherm model, with the adsorption kinetics of available second-order kinetic. Physical adsorption for MG and chemical adsorption for Pb(II) were confirmed by Dubinin-Radushkevich (D-R) isothermal adsorption model. The adsorption of Pb(II) and MG in real water samples were then studied. The FeO/Cu-MOFs was found to be recyclable for removal of Pb(II) and MG, can be explored as the potential adsorbent for waste water treatment

Core cis-element variation confers subgenome-biased expression of a transcription factor that functions in cotton fiber elongation

Cotton cultivars have evolved to produce extensive, long, seed-born fibers important for the textile industry, but we know little about the molecular mechanism underlying spinnable fiber formation. Here, we report how PACLOBUTRAZOL RESISTANCE 1 (PRE1) in cotton, which encodes a basic helix-loop-helix (bHLH) transcription factor, is a target gene of spinnable fiber evolution. Differential expression of homoeologous genes in polyploids is thought to be important to plant adaptation and novel phenotypes. PRE1 expression is specific to cotton fiber cells, upregulated during their rapid elongation stage and A-homoeologous biased in allotetraploid cultivars. Transgenic studies demonstrated that PRE1 is a positive regulator of fiber elongation. We determined that the natural variation of the canonical TATA-box, a regulatory element commonly found in many eukaryotic core promoters, is necessary for subgenome-biased PRE1 expression, representing a mechanism underlying the selection of homoeologous genes. Thus, variations in the promoter of the cell elongation regulator gene PRE1 have contributed to spinnable fiber formation in cotton. Overexpression of GhPRE1 in transgenic cotton yields longer fibers with improved quality parameters, indicating that this bHLH gene is useful for improving cotton fiber quality

Benefits of Levothyroxine Replacement Therapy on Nonalcoholic Fatty Liver Disease in Subclinical Hypothyroidism Patients

Objectives. To evaluate the effect of levothyroxine (LT4) replacement therapy on nonalcoholic fatty liver disease (NAFLD) in subclinical hypothyroidism (SCH) patients. Methods. This study was a post hoc analysis of a randomized controlled trial and involved 33 significant and 330 mild SCH patients. All of the significant SCH patients received LT4 supplement. The mild SCH patients were grouped as LT4 treated or not. After 15 months of follow-up, prevalence of NAFLD in each group was reevaluated. Subgroup analysis was conducted in mild SCH patients with dyslipidemia. Results. After treatment with LT4, the prevalence of NAFLD in significant SCH patients reduced from 48.5% to 24.2% (p=0.041). In mild SCH patients, prevalence of NAFLD and serum alanine aminotransferase (ALT) was not significantly affected by LT4 supplementation. Nonetheless, mild SCH patients with dyslipidemia who received LT4 treatment experienced decreases in the prevalence of NAFLD and serum ALT levels (p<0.05 for both). In contrast, these parameters remained comparably stable in patients who were not treated. Conclusion. LT4 supplementation has benefits on NAFLD in significant SCH patients or mild SCH patients with dyslipidemia. For NAFLD patients with SCH, appropriate supplementation of LT4 may be an effective means of controlling NAFLD. The original trial was registered with ClinicalTrials.gov (NCT01848171)