Past ultraviolet and optical observations of stars hosting close-in Jupiter-mass planets have shown that some of these stars present an anomalously low chromospheric activity, significantly below the ...basal level. For the hot Jupiter planet host WASP-13, observations have shown that the apparent lack of activity is possibly caused by absorption from the intervening interstellar medium (ISM). Inspired by this result, we study the effect of ISM absorption on activity measurements (S and log R 'HK indices) for main-sequence late-type stars. To this end, we employ synthetic stellar photospheric spectra combined with varying amounts of chromospheric emission and ISM absorption. We present the effect of ISM absorption on activity measurements by varying several instrumental (spectral resolution), stellar (projected rotational velocity, effective temperature, and chromospheric emission flux), and ISM parameters (relative velocity between stellar and ISM Ca ii lines, broadening b-parameter, and Ca ii column density). We find that for relative velocities between the stellar and ISM lines smaller than 30–40 km s-1 and for ISM Ca ii column densities log NCaII ⪆ 12, the ISM absorption has a significant influence on activity measurements. Direct measurements and three dimensional maps of the Galactic ISM absorption indicate that an ISM Ca ii column density of log NCaII = 12 is typically reached by a distance of about 100 pc along most sight lines. In particular, for a Sun-like star lying at a distance greater than 100 pc, we expect a depression (bias) in the log R 'HK value larger than 0.05–0.1 dex, about the same size as the typical measurement and calibration uncertainties on this parameter. This work shows that the bias introduced by ISM absorption must always be considered when measuring activity for stars lying beyond 100 pc. We also consider the effect of multiple ISM absorption components. We discuss the relevance of this result for exoplanet studies and revise the latest results on stellar activity versus planet surface gravity correlation. We finally describe methods with which it would be possible to account for ISM absorption in activity measurements and provide a code to roughly estimate the magnitude of the bias. Correcting for the ISM absorption bias may allow one to identify the origin of the anomaly in the activity measured for some planet-hosting stars.
Past UV and optical observations of stars hosting hot Jupiters have shown that some of these stars present an anomalously low chromospheric activity, significantly below the basal level. For WASP-13, ...observations have shown that the apparent lack of activity is possibly caused by absorption from the intervening ISM. Inspired by this result, we study the effect of ISM absorption on activity measurements (S and logR'\(_{\rm HK}\) indices) for main-sequence late-type stars. To this end, we employ synthetic stellar photospheric spectra combined with varying amounts of chromospheric emission and ISM absorption. We present the effect of ISM absorption on activity measurements by varying several instrumental, stellar, and ISM parameters. We find that for relative velocities between the stellar and ISM lines smaller than 30-40 km/s and for ISM CaII column densities logN\(_{\rm CaII}\)>12, the ISM absorption has a significant influence on activity measurements. Direct measurements and three dimensional maps of the Galactic ISM absorption indicate that an ISM CaII column density of logN\(_{\rm CaII}\)=12 is typically reached by a distance of about 100 pc along most sight lines. In particular, for a Sun-like star lying at a distance greater than 100 pc, we expect a depression (bias) in the logR'\(_{\rm HK}\) value larger than 0.05-0.1 dex, about the same size as the typical measurement and calibration uncertainties on this parameter. This work shows that the bias introduced by ISM absorption must always be considered when measuring activity for stars lying beyond 100 pc. We also consider the effect of multiple ISM absorption components. We discuss the relevance of this result for exoplanet studies.
Past ultraviolet and optical observations of stars hosting close-in Jupiter-mass planets have shown that some of these stars present an anomalously low chromospheric activity, significantly below the ...basal level. For the hot Jupiter planet host WASP-13, observations have shown that the apparent lack of activity is possibly caused by absorption from the intervening interstellar medium (ISM). Inspired by this result, we study the effect of ISM absorption on activity measurements (S and log R'(HK) indices) for main-sequence late-type stars. To this end, we employ synthetic stellar photospheric spectra combined with varying amounts of chromospheric emission and ISM absorption. We present the effect of ISM absorption on activity measurements by varying several instrumental (spectral resolution), stellar (projected rotational velocity, effective temperature, and chromospheric emission flux), and ISM parameters (relative velocity between stellar and ISM Ca II lines, broadening b-parameter, and Ca II column density). We find that for relative velocities between the stellar and ISM lines smaller than 30-40 km s(-1) and for ISM Ca II column densities log N-CaII greater than or similar to 12, the ISM absorption has a significant influence on activity measurements. Direct measurements and three dimensional maps of the Galactic ISM absorption indicate that an ISM Ca II column density of log N-CaII = 12 is typically reached by a distance of about 100 pc along most sight lines. In particular, for a Sun-like star lying at a distance greater than 100 pc, we expect a depression (bias) in the log R'(HK) value larger than 0.05-0.1 dex, about the same size as the typical measurement and calibration uncertainties on this parameter. This work shows that the bias introduced by ISM absorption must always be considered when measuring activity for stars lying beyond 100 pc. We also consider the effect of multiple ISM absorption components. We discuss the relevance of this result for exoplanet studies and revise the latest results on stellar activity versus planet surface gravity correlation. We finally describe methods with which it would be possible to account for ISM absorption in activity measurements and provide a code to roughly estimate the magnitude of the bias. Correcting for the ISM absorption bias may allow one to identify the origin of the anomaly in the activity measured for some planet-hosting stars.
Fasting induces specific molecular and metabolic adaptions in most organisms. In biomedical research fasting is used in metabolic studies to synchronize nutritional states of study subjects. Because ...there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular mechanisms in fasting.
We investigated the dynamic changes of liver gene expression and serum parameters of mice at several time points during a 48 hour fasting experiment and then focused on the global gene expression changes in epididymal white adipose tissue (WAT) as well as on pathways common to WAT, liver, and skeletal muscle. This approach produced several intriguing insights: (i) rather than a sequential activation of biochemical pathways in fasted liver, as current knowledge dictates, our data indicates a concerted parallel response; (ii) this first characterization of the transcriptome signature of WAT of fasted mice reveals a remarkable activation of components of the transcription apparatus; (iii) most importantly, our bioinformatic analyses indicate p53 as central node in the regulation of fasting in major metabolic tissues; and (iv) forced expression of Ddit4, a fasting-regulated p53 target gene, is sufficient to augment lipolysis in cultured adipocytes.
In summary, this combination of focused and global profiling approaches provides a comprehensive molecular characterization of the processes operating during fasting in mice and suggests a role for p53, and its downstream target Ddit4, as novel components in the transcriptional response to food deprivation.
The discovery of significant amounts of metabolically active brown adipose tissue (BAT) in adult humans renders it a promising target for anti-obesity therapies by inducing weight loss through ...increased energy expenditure. The components of the N-acetylaspartate (NAA) pathway are highly abundant in BAT. Aspartate N-acetyltransferase (Asp-NAT, encoded by Nat8l) synthesizes NAA from acetyl-CoA and aspartate and increases energy expenditure in brown adipocytes. However, the exact mechanism how the NAA pathway contributes to accelerated mobilization and oxidation of lipids and the physiological regulation of the NAA pathway remained elusive. Here, we demonstrate that the expression of NAA pathway genes corresponds to nutrient availability and specifically responds to changes in exogenous glucose. NAA is preferentially produced from glucose-derived acetyl-CoA and aspartate and its concentration increases during adipogenesis. Overexpression of Nat8l drains glucose-derived acetyl-CoA into the NAA pool at the expense of cellular lipids and certain amino acids. Mechanistically, we elucidated that a combined activation of neutral and lysosomal (acid) lipolysis is responsible for the increased lipid degradation. Specifically, translocation of the transcription factor EB to the nucleus activates the biosynthesis of autophagosomes and lysosomes. Lipid degradation within lysosomes accompanied by adipose triglyceride lipase-mediated lipolysis delivers fatty acids for the support of elevated mitochondrial respiration. Together, our data suggest a crucial role of the NAA pathway in energy metabolism and metabolic adaptation in BAT.
Background and Purpose
The antioxidant 5‐hydroxymethylfurfural (5‐HMF) exerts documented beneficial effects in several experimental pathologies and is currently tested as an antisickling drug in ...clinical trials. In the present study, we examined the cardiovascular effects of 5‐HMF and elucidated the mode of action of the drug.
Experimental Approach
The cardiovascular effects of 5‐HMF were studied with pre‐contracted porcine coronary arteries and rat isolated normoxic‐perfused hearts. Isolated hearts subjected to ischaemia/reperfusion (I/R) injury were used to test for potential cardioprotective effects of the drug. The effects of 5‐HMF on action potential and L‐type Ca2+ current (ICa,L) were studied by patch‐clamping guinea pig isolated ventricular cardiomyocytes.
Key Results
5‐HMF relaxed coronary arteries in a concentration‐dependent manner and exerted negative inotropic, lusitropic and chronotropic effects in rat isolated perfused hearts. On the other hand, 5‐HMF improved recovery of inotropic and lusitropic parameters in isolated hearts subjected to I/R. Patch clamp experiments revealed that 5‐HMF inhibits L‐type Ca2+ channels. Reduced ICa,L density, shift of ICa,L steady‐state inactivation curves toward negative membrane potentials and slower recovery of ICa,L from inactivation in response to 5‐HMF accounted for the observed cardiovascular effects.
Conclusions and Implications
Our data revealed a cardioprotective effect of 5‐HMF in I/R that is mediated by inhibition of L‐type Ca2+ channels. Thus, 5‐HMF is suggested as a beneficial additive to cardioplegic solutions, but adverse effects and contraindications of Ca2+ channel blockers have to be considered in therapeutic application of the drug.
Histone acetylation depends on the abundance of nucleo-cytoplasmic acetyl-CoA. Here, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. N-acetylaspartate (NAA) is a ...highly abundant brain metabolite catabolized by aspartoacylase yielding aspartate and acetate. The latter can be further used for acetyl-CoA production. Prior to this work, the presence of NAA has not been described in adipocytes. Here, we show that accumulation of NAA decreases the brown adipocyte phenotype. We increased intracellular NAA concentrations in brown adipocytes via media supplementation or knock-down of aspartoacylase and measured reduced lipolysis, thermogenic gene expression, and oxygen consumption. Combinations of approaches to increase intracellular NAA levels showed additive effects on lipolysis and gene repression, nearly abolishing the expression of Ucp1, Cidea, Prdm16, and Ppara. Transcriptome analyses of aspartoacylase knock-down cells indicate deficiencies in acetyl-CoA and lipid metabolism. Concordantly, cytoplasmic acetyl-CoA levels and global histone H3 acetylation were decreased. Further, activating histone marks (H3K27ac and H3K9ac) in promoters/enhancers of brown marker genes showed reduced acetylation status. Taken together, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. Thereby, we mechanistically connect the NAA pathway to the epigenomic regulation of gene expression, modulating the phenotype of brown adipocytes.
The importance of peroxisomes for adipocyte function is poorly understood. Herein, we provide insights into the critical role of peroxin 16 (PEX16)-mediated peroxisome biogenesis in adipocyte ...development and lipid metabolism. Pex16 is highly expressed in adipose tissues and upregulated during adipogenesis of murine and human cells. We demonstrate that Pex16 is a target gene of the adipogenesis “master-regulator” PPARγ. Stable silencing of Pex16 in 3T3-L1 cells strongly reduced the number of peroxisomes while mitochondrial number was unaffected. Concomitantly, peroxisomal fatty acid (FA) oxidation was reduced, thereby causing accumulation of long- and very long-chain (polyunsaturated) FAs and reduction of odd-chain FAs. Further, Pex16-silencing decreased cellular oxygen consumption and increased FA release. Additionally, silencing of Pex16 impaired adipocyte differentiation, lipogenic and adipogenic marker gene expression, and cellular triglyceride stores. Addition of PPARγ agonist rosiglitazone and peroxisome-related lipid species to Pex16-silenced 3T3-L1 cells rescued adipogenesis. These data provide evidence that PEX16 is required for peroxisome biogenesis and highlights the relevance of peroxisomes for adipogenesis and adipocyte lipid metabolism.
•Pex16 is a PPARγ target gene.•Pex16 expression regulates peroxisomal number and lipid metabolism.•Pex16 is required for adipogenesis.
IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of ...the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.
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