bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omental 11β‐hydroxysteroid Dehydrogenase 1 Correlates with Fat Cell Size Independently of Obesity
Authors: Michailidou Zoi , Jensen Michael D. , Dumesic Daniel A. , Chapman Karen E. , Seckl Jonathan R. , Walker Brian R. , Morton Nicholas M. 
Published: July 2008

AbstractObjectives: In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1), or glucocorticoid receptor (GRα) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11βHSD1 and GRα mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome.Research Methods and Procedures: Adipose tissue biopsies were collected from subcutaneous (abdominal, thigh, gluteal) and intra‐abdominal (omental) adipose depots from 21 women. 11βHSD1 and GRα mRNA levels were measured by real‐time polymerase chain reaction. Body composition, fat distribution, fat cell size, and blood lipid, glucose, and insulin levels were measured.Results: 11βHSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p < 0.001) depots and was positively correlated with BMI and visceral adiposity in all depots. Omental 11βHSD1 correlated with percent body fat (R = 0.462, p < 0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p < 0.05). Conversely, GRα mRNA was highest in omental fat (p < 0.001). GRα mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = −0.589, p < 0.05) and omental depots (R = −0.627, p < 0.05). Omental GRα mRNA was inversely associated with visceral adiposity (R = −0.507, p < 0.05), fat cell size (R = −0.52, p < 0.01), and triglycerides (R = −0.50, p < 0.05).Discussion: Obesity was associated with elevated 11βHSD1 mRNA in all adipose compartments. GRα mRNA is reduced in the omental depot with obesity. The novel correlation of 11βHSD1 with omental fat cell size, independent of obesity, suggests that intracellular cortisol regeneration is a strong predictor of hypertrophy in the omentum.
Transcriptomic Characterization of the Long‐term Dihydrotestosterone Effects in Adipose Tissue
Authors: Bolduc Carl , Yoshioka Mayumi , St Amand Jonny 
Published: July 2008

AbstractObjective: To study the long‐term transcriptomic effects of dihydrotestosterone (DHT) in adipose tissue. Fat distribution is regulated by sexual hormones. It is still unclear if androgens are promoting or reducing intra‐abdominal fat accumulation.Research Methods and Procedures: Retroperitoneal adipose tissue were isolated from each group of gonadectomized (GDX) C57BL6 male mice treated with vehicle or DHT for 21 days. Serial analysis of gene expression (SAGE) was performed to generate ∼150,000 SAGE tags from each sample.Results: Among the numerous genes regulated by DHT, transcripts involved in glycolysis, such as aldolase 1 A isoform and pyruvate kinase muscle as well as lipogenic transcripts, such as malic enzyme supernatant and ELOVL family member 6 elongation of long chain fatty acids were down‐regulated by androgen supplementation. In contrast, transcripts involved in lipolysis and fatty acid oxidation, such as carboxylesterase 3, acetyl‐coenzyme A acyltransferase 1, 3‐ketoacyl‐CoA thiolase B and enoyl‐coenzyme A hydratase/3‐hydroxyacyl coenzyme A dehydrogenase were up‐regulated by DHT. Pro‐apoptotic transcripts such as cell death‐inducing DFFA‐like effector c, BCL2/adenovirus E1B 19 kDa‐interacting protein 1 NIP3 and ‐interacting protein 3‐like were up‐regulated by DHT, whereas transcripts involved in promotion of cell cycle such as cyclin D2 were down‐regulated by DHT.Discussion: These results suggest that chronic androgen treatment may help to improve metabolic profile by regulating various critical pathways involved in adipose tissue physiology. In addition, several genes associated with a healthier metabolic profile, such as adiponectin and CD36 antigen, were up‐regulated by 21 days of DHT treatment.
Dehydroepiandrosterone Sulfate and High‐density Lipoprotein‐cholesterol Levels in Overweight Children
Authors: Garcés Carmen , Cano Beatriz , Lasunción Miguel A. , Mangas Alipio , Benavente Mercedes , De Oya Iría , Studer Alexis , De Oya Manuel 
Published: July 2008

AbstractObjective: The association of childhood overweight with cardiovascular risk factors seems to change by sex and age, which may indicate that hormonal status could be the cause of this different association. In this study, we analyzed the relationship of dehydroepiandrosterone sulfate (DHEA‐S) with the alterations associated with overweight by analyzing the influence of this hormone in the differences found in biochemical variables between normal‐weight and overweight prepubertal children.Research Methods and Design: The study included 684 6‐ to 8‐year‐old children (350 boys and 334 girls) categorized by the presence or absence of overweight, according to the age‐ and sex‐specific cut‐off points proposed for children. Lipid levels were determined by standard methods. DHEA‐S and insulin levels were measured by radioimmunoassay. Biochemical variables were compared between normal‐weight and overweight children by tertiles of DHEA‐S.Results: We observed that plasma high‐density lipoprotein‐cholesterol (HDL‐C) and apolipoprotein (apo)‐AI levels were significantly lower in overweight than in normal‐weight boys only in the highest tertile of DHEA‐S. No significant differences in plasma glucose levels, total cholesterol, low‐density lipoprotein‐cholesterol, or apo B were found between overweight and normal‐weight children in any DHEA‐S tertile. In a Spearman correlation analysis, we observed a significant and negative correlation for weight and BMI with HDL‐C and for weight and apo‐AI levels only in the highest tertile of DHEA‐S.Discussion: Our study showed that, in our prepubertal population, the association of overweight with decreased HDL‐C and apo‐AI levels was present only in boys within the highest levels of DHEA‐S, supporting the importance of hormonal influences on the association of metabolic alterations with overweight.
Effects of Pronounced Weight Loss on Adiponectin Oligomer Composition and Metabolic Parameters
Authors: Engl Julia , Bobbert Thomas , Ciardi Christian , Laimer Markus , Tatarczyk Tobias , Kaser Susanne , Weiss Helmut , Molnar Clemens , Tilg Herbert , Patsch Josef R. , Spranger Joachim , Ebenbichler Christoph F. 
Published: July 2008

AbstractObjective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters.Research Methods and Procedures: Thirteen severely obese female subjects were examined before and 1 year after surgical treatment. Total adiponectin was determined by radioimmunosorbent assay, and oligomer composition was detected by nondenaturing Western blot.Results: BMI decreased substantially (p < 0.001), which was associated with an increase of total adiponectin from 12.9 ± 5.9 to 14.3 ± 6.1 μg/mL (p = 0.055). Medium molecular weight (MMW) adiponectin increased from 7.5 ± 3.6 to 9.1 ± 4.1 μg/mL (p = 0.009), whereas high (HMW) and low molecular weight adiponectin remained unchanged. Δ values of total adiponectin correlated significantly with Δ values of anthropometric parameters. Similar correlations were found for Δ values of MMW (Δ weight: r2 = 0.4132, p = 0.0178; Δ BMI: r2 = 0.3319, p = 0.0393; Δ fat mass: r2 = 0.5202, p = 0.0054).Discussion: Thus, profound weight loss was associated with an increase in total adiponectin, which was mainly and consistently caused by increases in MMW adiponectin (p = 0.009). These changes result in a shift from low molecular weight to MMW and HMW adiponectin isoforms, which may be related to improvements in both anthropometric and metabolic parameters.
Probable Blind Spot in the International Diabetes Federation Definition of Metabolic Syndrome
Authors: Chen Hsin‐Jen , Pan Wen‐Harn 
Published: July 2008

AbstractObjectives: The International Diabetes Federation (IDF) proposed a novel definition of the metabolic syndrome (MS) in 2005, which designated central obesity as mandatory. The new National Cholesterol Education Program (NCEP) version, announced by the American Heart Association and National Heart Lung and Blood Institute in October 2005, did not favor any of the five components. We set out to compare the cardiovascular profiles of patients cross‐defined by these two definitions to shed light on the differential meanings of the two.Research Methods and Procedures: We analyzed data from 2608 non‐institutionalized adults (≥19 years old) in the National Nutrition and Health Survey in Taiwan, who had complete data for the five MS defining components. Both definitions adopted lower cut‐points for fasting glucose and race‐specific cut‐points for waist circumference.Results: Under the IDF's and new NCEP's definitions, the MS prevalence was 6.2% and 11.6% in men and 12.6% and 16.5% in women, respectively. Although the two definitions had high agreement, IDF failed to pick up ∼4% to 5% of people with more than three MS component disorders but a waist circumference less than the cut‐point. Subjects whose physical conditions only satisfied NCEP's definition had similar or worse metabolic profiles than those whose conditions satisfied both IDF's definition and the new NCEP's definition.Discussion: The IDF definition would fail to identify a portion of people who have more than three MS component disorders but a small waistline. Further research and discussion are needed on whether and how to implement the IDF's definition.
Changes in Body Composition with Weight Loss: Obese Subjects Randomized to Surgical and Medical Programs
Authors: Dixon John B. , Strauss Boyd J. G. , Laurie Cheryl , O'Brien Paul E. 
Published: July 2008

AbstractObjective: To assess changes in body composition with weight loss in obese subjects randomized to a laparoscopic adjustable gastric band surgical program or a medical program using a very‐low‐energy diet and orlistat.Research Methods and Procedures: Using body composition measurements by DXA, neutron activation for total body nitrogen, and whole body γ counting for total body potassium, we studied changes in fat mass, fat distribution, fat‐free mass, total bone mineral content, total body protein, and body cell mass at 6 (n = 61 paired) and 24 months (n = 53 paired) after randomization.Results: At 24 months, the surgical group had lost significantly more weight (surgical, 20.3 ± 6.5 kg; medical, 5.9 ± 8.0 kg). There was favorable fat‐free mass to fat mass loss ratios for both groups (surgical, 1:5.5; medical, 1:5.9). Changes in total body nitrogen or potassium were favorable in each group. A small reduction in mean bone mineral content occurred throughout the study but was not associated with extent of weight loss or treatment group. At 6 months, weight loss for both groups was similar (surgical, 14.1 ± 4.5 kg; medical, 13.3 ± 7.3 kg). The medical program subjects lost less fat‐free mass and skeletal muscle and had increased total body protein. The proportion of body fat to limb fat remained remarkably constant throughout the study.Discussion: Weight loss programs used in this study induced fat loss without significant deleterious effects on the components of fat‐free mass.
Body Mass, DRD4, Physical Activity, Sedentary Behavior, and Family Socioeconomic Status: The Add Health Study
Authors: Guo Guang , North Kari E. , Gorden‐Larsen Penny , Bulik Cynthia M. , Choi Seulki 
Published: July 2008

AbstractObjective: To investigate the joint role of the 48‐base pair repeat polymorphism of the dopamine receptor 4 gene (DRD4) and environmental factors in body mass variation among an ethnically diverse sample of U.S. adolescents and young adults.Research Methods and Procedures: Approximately 2600 adolescent and young adults in the National Longitudinal Study of Adolescent Health (Add Health) who provided DNA measures and measures of height and weight were included in the analysis. Mixed regression modeling was used to investigate the effects of the 7R/7R and any5R variants in the DRD4 gene simultaneously with the effects of physical activity (PA), sedentary behavior (SB), and family socioeconomic status (SES) on body mass variation. European Americans, African Americans, and Hispanic Americans were modeled separately.Results and Discussion: Both the 7R/7R and any5R genotypes of the DRD4 gene were associated with age‐ and sex‐specific BMI percentile score (BMI‐P) based on the Centers for Disease Control and Prevention/National Center for Health Statistics 2000 reference curves among African Americans and only among African Americans (N = 413) 20 years old or younger. Neither genetic variants are associated with the BMI measure among white (N = 1386) and Hispanic‐American (N = 331) adolescents. The presence of the 7R/7R genotype was associated with a reduction of 15.1 in BMI percentile (p = 0.005), and the presence of any5R was associated with an increase of 15.5 in BMI percentile (p = 0.003), after adjusting for PA, SB, and family SES. Neither PA nor SB as measured in Add Health is importantly associated with BMI‐P, suggesting a complex relationship between body mass and PA/SB among adolescents and young adults. Family SES is negatively related to BMI‐P in the European‐American sample.
A possible biochemical link between NADPH oxidase (Nox) 1 redox-signalling and ERp72
Authors: Chen Wei , Shang Wei Hao , Adachi Yoshifumi , Hirose Kunitaka , Ferrari David M. , Kamata Tohru 
Published: July 2008

Emerging evidence indicates that Nox (NADPH oxidase) 1-generated ROS (reactive oxygen species) play critical regulatory roles in various cellular processes, yet little is known of direct targets for the oxidase. In the present study we show that one of the proteins selectively oxidized in response to Nox1-generated ROS was ERp72 (endoplasmic reticulum protein 72 kDa) with TRX (thioredoxin) homology domains. Oxidation of ERp72 by Nox1 resulted in an inhibition of its reductase activity. EGF treatment of cells stimulated the Nox1 activity and the activated Nox1 subsequently mediated EGF-induced suppression of the ERp72 reductase activity. Co-immunoprecipitation, GST (glutathione transferase) pulldown assays and mutational analysis, indicated that Nox1 associates with ERp72, which involves its N-terminus encompassing a Ca2+-binding site and the first TRX-like motif. Furthermore, confocal microscopy showed co-localization between Nox1 and ERp72 at the plasma membrane. These results suggest that Nox1 functionally associates with ERp72, regulating redox-sensitive signalling pathways in a cellular context.
Association of human DNA helicase RecQ5β with RNA polymerase II and its possible role in transcription
Authors: Izumikawa Keiichi , Yanagida Mitsuaki , Hayano Toshiya , Tachikawa Hiroyuki , Komatsu Wataru , Shimamoto Akira , Futami Kazunobu , Furuichi Yasuhiro , Shinkawa Takashi , Yamauchi Yoshio , Isobe Toshiaki , Takahashi Nobuhiro 
Published: July 2008

Although RecQ5β is a ssDNA (single-stranded DNA)-stimulated ATPase and an ATP-dependent DNA helicase with strand-annealing activities, its cellular function remains to be explored. In the present paper, we used immunopurification and MS-based analyses to show that human DNA helicase RecQ5β is associated with at least four RNAP II (RNA polymerase II) subunits. RecQ5β was also present in complexes immunoprecipitated using three different antibodies against the large subunit of RNAP II, or in complexes immunoprecipitated using an anti-FLAG antibody against either FLAG–RNAP II 33 kDa subunit or FLAG–Pin1. Different regions of the non-helicase domain of the RecQ5β molecule were associated with hypophosphorylated and hyperphosphorylated forms of the RNAP II large subunit independently of DNA and RNA. RecQ5β was also found in nuclear chromatin fractions and associated with the coding regions of the LDL (low-density lipoprotein) receptor and β-actin genes. Knockdown of the RecQ5β transcript increased the transcription of those genes. The results of the present study suggest that RecQ5β has suppressive roles in events associated with RNAP II-dependent transcription.
Reduction of S-nitrosoglutathione by alcohol dehydrogenase 3 is facilitated by substrate alcohols via direct cofactor recycling and leads to GSH-controlled formation of glutathione transferase inhibitors
Authors: Staab Claudia A. , Ålander Johan , Brandt Margareta , Lengqvist Johan , Morgenstern Ralf , Grafström Roland C. , Höög Jan-Olov 
Published: July 2008

GSNO (S-nitrosoglutathione) is emerging as a key regulator in NO signalling as it is in equilibrium with S-nitrosated proteins. Accordingly, it is of great interest to investigate GSNO metabolism in terms of competitive pathways and redox state. The present study explored ADH3 (alcohol dehydrogenase 3) in its dual function as GSNOR (GSNO reductase) and glutathione-dependent formaldehyde dehydrogenase. The glutathione adduct of formaldehyde, HMGSH (S-hydroxymethylglutathione), was oxidized with a kcat/Km value approx. 10 times the kcat/Km value of GSNO reduction, as determined by fluorescence spectroscopy. HMGSH oxidation in vitro was greatly accelerated in the presence of GSNO, which was concurrently reduced under cofactor recycling. Hence, considering the high cytosolic NAD+/NADH ratio, formaldehyde probably triggers ADH3-mediated GSNO reduction by enzyme-bound cofactor recycling and might result in a decrease in cellular S-NO (S-nitrosothiol) content in vivo. Formaldehyde exposure affected S-NO content in cultured cells with a trend towards decreased levels at concentrations of 1–5 mM, in agreement with the proposed mechanism. Product formation after GSNO reduction to the intermediate semimercaptal responded to GSH/GSNO ratios; ratios up to 2-fold allowed the spontaneous rearrangement to glutathione sulfinamide, whereas 5-fold excess of GSH favoured the interception of the intermediate to form glutathione disulfide. The sulfinamide and its hydrolysis product, glutathione sulfinic acid, inhibited GST (glutathione transferase) activity. Taken together, the findings of the present study provide indirect evidence for formaldehyde as a physiological trigger of GSNO depletion and show that GSNO reduction can result in the formation of GST inhibitors, which, however, is prevented under normal cellular redox conditions.
Functional characterization of ribosomal P1/P2 proteins in human cells
Authors: Martinez-Azorin Francisco , Remacha Miguel , Ballesta Juan P. G. 
Published: July 2008

The ‘stalk’ is a large ribosomal subunit domain that regulates translation. In the present study the role of the ribosomal stalk P proteins in modulating ribosomal activity has been investigated in human cells using RNA interference. A strong down-regulation of P2 mRNA and a drastic decrease in P2 protein in a stable human cell line was achieved using a doxycycline-inducible system. Interestingly, the amount of P1 protein was similarly decreased in these cells, in contrast with the expression of P1 mRNA. The loss of P1/P2 proteins produced a decrease in the growth rate of these cells, as well as an altered polysome pattern with reduced translation efficiency, but without affecting the free 40 S/60 S subunit ratio. A decrease in the ribosomal-subunit joining capacity was also observed. These data indicate that P1/P2 proteins modulate cytoplasmic translation by influencing the interaction between subunits, thereby regulating the rate of cell proliferation.
A requirement for thioredoxin in redox-sensitive modulation of T-cadherin expression in endothelial cells
Authors: Joshi Manjunath B. , Ivanov Danila , Philippova Maria , Kyriakakis Emmanouil , Erne Paul , Resink Thérèse J. 
Published: July 2008

T-cad (T-cadherin), a glycosylphosphatidylinositol-anchored cadherin superfamily member, is expressed widely in the brain and cardiovascular system, and absent, decreased, or even increased, in cancers. Mechanisms controlling T-cad expression are poorly understood. The present study investigated transcriptional regulation of T-cad in ECs (endothelial cells). Conditions of oxidative stress (serum-deprivation or presence of H2O2) elevate T-cad mRNA and protein levels in ECs. Reporter gene analysis, using serially deleted T-cad promoter stretches ranging from −99 to −2304 bp, located the minimal promoter region of T-cad within −285 bp from the translation start site. Reporter activity in ECs transfected with the −285 bp construct increased under conditions of oxidative stress, and this was normalized by antioxidant N-acetylcysteine. An electrophoretic-mobility-shift assay revealed a specific nucleoprotein complex unique to −156 to −203 bp, which increased when nuclear extracts from oxidatively stressed ECs were used, suggesting the presence of redox-sensitive binding element(s). MS analysis of the nucleoprotein complex unique to −156 to −203 bp after streptavidin–agarose pull-down detected the presence of the redox-active protein thioredoxin. The presence of thioredoxin-1 in a nuclear extract from oxidatively stressed ECs was demonstrated after immunoprecipitation and immunoblotting. Transfection of ECs with thioredoxin-1 small interfering RNA abrogated oxidative-stress-induced up-regulation of T-cad transcripts and protein. We conclude that thioredoxin-1 is an important determinant of redox-sensitive transcriptional up-regulation of T-cad in ECs.
CD95 ligation and intracellular membrane flow
Authors: Reinehr Roland , Häussinger Dieter 
Published: July 2008

Whereas ligation of the CD95 death receptor in the plasma membrane of so-called type I cells leads to a direct caspase 8-dependent activation of downstream effector caspases, mitochondrial amplification of caspase 8-derived signals is required in so-called type II cells in order to execute apoptotic cell death. In type I cells CD95L (CD95 ligand) binding to CD95 results in a ceramide-dependent formation of the DISC (death-inducing signalling complex) and caspase 8-dependent CD95 clustering in the plasma membrane, followed by an internalization of these multimeric-receptor–DISC complexes. In contrast, in the hepatocyte, a type II cell, the bulk of CD95 is stored intracellularly under resting conditions and only a few ‘sentinel’ CD95 receptors are present in the plasma membrane. However, their activation by CD95L is sufficient to trigger a caspase 8-dependent endosomal acidification and a ceramide-dependent trafficking of intracellularly stored CD95 to the plasma membrane, thereby amplifying CD95 activation. Thus, in both type I and type II cells, ceramide and CD95 receptor endo- and exo-cytosis are involved in CD95-mediated apoptosis, but apparently in different ways. This, however, is not the only effect of CD95 ligation on intracellular membrane flow in type II cells, and evidence has been presented that soon after CD95 ligation Golgi elements intermix caspase-dependently with mitochondria. In this issue of the Biochemical Journal, Matarrese et al. report another aspect on endocytosis in response to CD95 ligation in type II cells, namely a caspase-independent endocytosis with vesicle translocation to the mitochondrial compartment, suggestive of an interplay between both organelles in the sense of an ‘organelle scrambling’. Thus early effects of CD95 activation on intracellular membrane flow may be much more complex than previously thought, but much has still to be learned about signalling mechanisms and the role they play in apoptosis.