Wolfgang Patsch

• Paracelsus Medical University

The transcriptional regulator peroxisome proliferator activated receptor gamma coactivator 1A (PGC-1α), encoded by PPARGC1A, has been linked to neurodegenerative diseases. Recently discovered CNS-specific PPARGC1A transcripts are initiated far upstream of the reference promoter, spliced to exon 2 of the reference gene, and are more abundant than re...

O-GlcNAcylation is a post-translational modification of proteins that controls a variety of cellular processes, is chronically elevated in diabetes mellitus, and may contribute to the progression of diabetic complications, including diabetic nephropathy. Our previous work showed that increases in the O-GlcNAcylation of cellular proteins impair the...

Background The APOE ‐ε4 allele is an established risk factor for Alzheimer's disease (AD). TOMM40 located adjacent to APOE has also been implicated in AD but reports of TOMM40 associations with AD that are independent of APOE ‐ε4 are at variance. Methods We investigated associations of AD with haplotypes defined by three TOMM40 and two APOE single...

PPARGC1A encodes a transcriptional co-activator also termed peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC-1α) which orchestrates multiple transcriptional programs. We have recently identified CNS-specific transcripts that are initiated far upstream of the reference gene (RG) promoter. The regulation of these isofo...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

IClswell is the chloride current induced by cell swelling, and plays a fundamental role in several biological processes, including the regulatory volume decrease (RVD). ICln is a highly conserved, ubiquitously expressed and multifunctional protein involved in the activation of IClswell. In platelets, ICln binds to the intracellular domain of the in...

Clswell is the chloride current induced by cell swelling, and plays a fundamental role in several biological processes, including the regulatory volume decrease (RVD). ICln is a highly conserved, ubiquitously expressed and multifunctional protein involved in the activation of IClswell. In platelets, ICln binds to the intracellular domain of the int...

Several studies have shown site-specific differences in colorectal cancer (CRC) with respect to the risk factors. CRC was shown to be associated with cardiovascular risk (CVR) factors, but site-specific variations have not been investigated so far. This study aimed to assess the associations between the prevalence and subsite-specific differences o...

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. PGC-1α, encoded by PPARGC1A, is a transcriptional co-activator that has been implicated in the pathogenesis of neurodegenerative disorders. We recently discovered multiple new PPARGC1A transcripts that initiate from a novel promoter located far upstream of the r...

Introduction: -: As a small proportion of obese individuals do not develop metabolic complications and non-alcoholic fatty liver disease (NAFLD), this study aimed to provide a comprehensive clinical, metabolic and genetic description of obese subjects with healthy livers. Methods: -: A total of 183 subjects were stratified, according to BMI, pre...

Background/Aims: In the human genome, more than 400 genes encode ion channels, which are ubiquitously expressed and often coexist and participate in almost all physiological processes. Therefore, ion channel blockers represent fundamental tools in discriminating the contribution of individual channel types to a physiological phenomenon. However, un...

The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration...

Background/aim: Accurate genotyping of CYP2D6 is challenging due to its inherent genetic variation, copy number variation (duplications and deletions) and hybrid formation with highly homologous pseudogenes. Because a relatively high percentage (∼25%) of clinically prescribed drugs are substrates for this enzyme, accurate determination of its geno...

Methods: Real-time PCR and pyrosequencing were used to respectively quantify pendrin mRNA levels and methylation of pendrin promoter, with and without IL-4 stimulation, in healthy and diseased primary HBE cells, as well as NCI-H292 cells. Results: Increases in pendrin mRNA after IL-4 stimulation was more robust in NCI-H292 cells than in primary...

Objectives: Regular aerobic exercise provides beneficial effects on human health and reduces all-cause mortality. Aerobic exercise has profound metabolic effects, and specific metabolites may reflect physiological changes. We aimed to identify endogenous metabolites that distinguish the trained from the untrained state to increase the spectrum of...

Objective: Elevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. Methods: In a cros...

Objectives: Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity; however, 5-8% of lean subjects also have evidence of NAFLD. We aimed to investigate clinical, genetic, metabolic and lifestyle characteristics in lean Caucasian subjects with NAFLD. Methods: Data from 187 subjects allocated to one of the three groups according to...

Background: Recent findings revealed negative effects of deregulated molecular circadian rhythm in coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Physical exercise training (ET) has been shown to promote anti-diabetic and anti-atherogenic responses in skeletal muscle of these patients, but the role of the circadian clock-machin...

Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue occasionally reveals normal histology. Long term follow-up of such patients has not been performed. We identified a total 70 subjects from our LB database with elevated liver tests and normal liver histology after a mean of 90.5±...

Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screeni...

Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insulin resistance. While lifestyle t...

Supplementary Material contains 17 Supplementary Tables showing additional clinical data of study subjects, sequences of primers used for PCR and generation of in vitro translation and eGFP constructs, genotypes by SNPs and sex, pairwise linkage disequilibria between SNPs and associations of haplotypes with traits by sex.

Background and Aims: Along the progression from normal colonic mucosa to colorectal cancer systemic metabolic pathways may be affected. We aimed to identify metabolic features and possible biomarkers of colorectal carcinoma and advanced adenoma. Methods: According to the results of screening colonoscopy 402 patients were allocated to one of 3 group...

Background The effect of vitamin D on colorectal adenomas may vary with regard to gender, localisation and histological type of the lesion. AimTo define the role of vitamin D and gender in a Caucasian cohort of subjects undergoing screening colonoscopy after consideration of established risk factors. Methods One thousand five hundred and thirty-two...

Obesity and diabetes affect more than half a billion individuals worldwide. Interestingly, the two conditions do not always coincide and the molecular determinants of “healthy” versus “unhealthy” obesity remain ill-defined. Chronic metabolic inflammation (metaflammation) is believed to be pivotal. Here, we tested a hypothesized anti-inflammatory ro...

Vitamin D (Vit D) deficiency may be linked to the development of obesity-associated complications such as insulin resistance and type 2 diabetes. We therefore evaluated the relationship of Vit D serum concentrations with metabolic parameters and type 2 diabetes in middle-aged Caucasian men and women. One thousand six hundred and thirty-one Caucasia...

Genetic modifiers are important clues for the identification of therapeutic targets in neurodegenerative diseases. Huntington disease (HD) is one of the most common autosomal dominant inherited neurodegenerative diseases. The clinical symptoms include motor abnormalities, cognitive decline and behavioral disturbances. Symptom onset is typically bet...

Abstract Background: It was the aim of this study to assess the effects of skiing on copper and iron parameters, since low copper and elevated body iron stores are associated with cardiovascular risk factors. Methods: Forty-seven middle-aged men and women (62-76 yrs) were allocated either to a guided 12-week skiing program (N=27) or their usual lif...

Background: Pendrin, an anion exchanger associated with the inner ear, thyroid and kidney, plays a significant role in respiratory tissues and diseases, where its expression is increased following IL-4 and IL-13 exposure. The mechanism leading to increased pendrin expression is in part due to binding of STAT6 to a consensus sequence (N4 GAS motif)...

One of the most pressing challenges in the post genomic era is the identification and characterization of protein-protein interactions (PPIs), as these are essential in understanding the cellular physiology of health and disease. Experimental techniques suitable for characterizing PPIs (X-ray crystallography or nuclear magnetic resonance spectrosco...

Increased visceral fat is associated with a high risk of diabetes and metabolic syndrome and is in part caused by excessive glucocorticoids (GCs). However, the molecular mechanisms remain undefined. We now identify the GC-dependent gene LIM domain only 3 (LMO3) as being selectively upregulated in a depot-specific manner in human obese visceral adip...

siCtrl- or siLMO3-tansfected hASCs derived from matched human SAT and VAT and pooled from n = 3 different donors treated with DMSO or HC for 24 hr. mRNA expression profiles were generated with human Gene 1.0 ST Arrays and processed as described in the Experimental Procedures. First, genes responsive to HC were tabulated if the fold change (HC versu...

mRNA profiling of siCtrl- or siLMO3-transfected hASCs differentiated into mature adipocytes. Total RNA was isolated at day 0 and day 6 of differentiation and subjected to DNA microarray analysis with Gene 1.0 ST arrays as described in the Experimental Procedures. Clusters 1 and 2 contain genes responsive to the adipogenic cocktail in siCtrl-treated...

hASCs were treated with 1 μM Dex in growth medium, and total RNA was isolated every 24 hr from day 0 up to day 5. mRNA expression profiles were generated with human Gene 1.0 ST Arrays and processed as described in the Experimental Procedures. Genes exhibiting more than a ±3-fold change relative to control treatment (in at least three out of five co...

Background & Aims: Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue occasionally reveals normal histology. Long-term follow-up of such patients has not been performed. Methods: We identified a total 70 subjects from our LB database with elevated liver tests and normal liver his...

Amyotrophic lateral sclerosis (ALS) is a devastating, adult-onset neurodegenerative disorder of the upper and lower motor systems. It leads to paresis, muscle wasting and inevitably to death, typically within 3 to 5 years. However, disease onset and survival vary considerably ranging in extreme cases from a few months to several decades. The geneti...

Background Huntington disease (HD) is caused by an autosomal dominant CAG repeat expansion in the htt gene. HD symptoms include neurologic, psychiatric and cognitive and metabolic abnormalities. In addition to the CAG repeat mutation other genetic factors termed disease modifiers determine symptom onset and disease progression. Some evidence sugges...

Background: Resistance training has become a mainstay of exercise training in type 2 diabetes mellitus (T2DM). However, it remains controversial whether hypertrophy resistance training (HRT) is superior to endurance resistance training (ERT) with regard to its effects on glycaemic control, muscle mass and strength. Methods: Thirty-two patients w...

PGC-1α has been implicated in the pathogenesis of neurodegenerative disorders. Several single-nucleotide polymorphisms (SNPs) located in two separate haplotype blocks of PPARGC1A have shown associations with Huntington's disease (HD) and Parkinson's disease, but causative SNPs have not been identified. One SNP (rs7665116) was located in a highly co...

Genetic studies implicated upstream stimulatory factor 1 (USF1) in familial combined hyperlipidemia because the rs2073658 minor allele was associated with reduced risk of familial combined hyperlipidemia and related disorders. The molecular mechanisms whereby rs2073658 influences trait expression have remained elusive. Plasma lipids, rs2073658 geno...

Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy...

Frequencies (%) of control region (CR) polymorphisms in patients with CNV and in controls as well as the corresponding odds ratios and 95% confidence intervals. (DOC)

Frequencies (%) of control region (CR) polymorphisms in patients with dry AMD and in controls as well as the corresponding odds ratios and 95% confidence intervals. (DOC)

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Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional coactivator that contributes to the regulation of numerous transcriptional programs including the hepatic response to fasting. Mechanisms at transcriptional and post-transcriptional levels allow PGC-1α to support distinct biological pathways. Here we describe...

Pendrin (SLC26A4, PDS) is an electroneutral anion exchanger transporting I -, Cl -, HCO3-, OH -, SCN - and formate. In the thyroid, pendrin is expressed at the apical membrane of the follicular epithelium and may be involved in mediating apical iodide efflux into the follicle; in the inner ear, it plays a crucial role in the conditioning of the pH...

To assess the potential role of FoxP3-expressing regulatory T cells (Tregs) in reversing obesity-linked insulin resistance and diabetic nephropathy in rodent models and humans. To characterize the role of Tregs in insulin resistance, human visceral adipose tissue was first evaluated for Treg infiltration and second, the db/db mouse model was evalua...

Numerous studies have shown that treatment of the modifiable cardiovascular risk factors (CVRF) results in a decreased risk to suffer from stroke or myocardial infarction. Despite the fact that exercise training is a potent treatment choice for CVRF, this is the first randomized study to assess the effects of alpine skiing on CVRF in elderly skiers...

Alpine skiing and ski training involves elements of static and dynamic training, and may therefore improve insulin sensitivity. Healthy men and women who where beginners/intermediate level of alpine skiing, were studied before (Pre) and immediately after (Post) 12 weeks of alpine ski training. After an additional 8 weeks a third test (retention stu...

To determine whether different complement factor H (CFH) genotypes play a role in treatment of age-related macular degeneration (AMD) with intravitreal bevacizumab. In this prospective study, we included 197 patients with exudative AMD and treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was...

T cells and level of the cytokine interferon-γ (IFN-γ) are increased in adipose tissue in obesity. Hedgehog (Hh) signaling has been shown to potently inhibit white adipocyte differentiation. In light of recent findings in neurons that IFN-γ and Hh signaling cross-talk, we examined their potential interaction in the context of adipogenesis. We used...

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of insulin resistance (IR) and IR is associated with an increased risk of colorectal carcinoma (CRC). Increased echogenicity suggesting NAFLD is a frequent incidental finding on ultrasound examination. We aimed to systematically evaluate whether NAFLD is an i...

HDL modifying effects of cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) depend in part on each other. We studied associations of CETP-Taq1B and -514C>T-LIPC polymorphisms with hepatic mRNA levels, and their combined effects on plasma lipids and carotid atherosclerosis. We genotyped the CETP-Taq1B and the -514C>T-LIPC polymorphi...

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of insulin resistance (IR), and IR is associated with an increased risk of colorectal carcinoma (CRC). Increased echogenicity suggesting NAFLD is a frequent incidental finding on ultrasound examination. We aimed to systematically evaluate whether NAFLD is an independent risk fact...

CR polymorphisms with a frequency greater 5% in controls and patients with T2DM recruited at the University Hospital Graz. (DOC)

CR polymorphisms with a frequency greater 5% in controls and patients with CAD. (DOC)

The pivotal role of mitochondria in energy production and free radical generation suggests that the mitochondrial genome could have an important influence on the expression of multifactorial age related diseases. Substitution of T to C at nucleotide position 16189 in the hypervariable D-loop of the control region (CR) of mitochondrial DNA (mtDNA) h...

Organic anion transporters (OATs) are anion exchangers that transport small hydrophilic anions and diuretics, antibiotics, nonsteroidal anti-inflammatory drugs, antiviral nucleoside analogs, and antitumor drugs across membrane barriers of epithelia of diverse organs. Three OATs are present in human liver: OAT2, OAT5, and OAT7. Given that hepatocyte...

To the Editor: The universal definition of myocardial infarction includes the increase and/or decrease in cardiac biomarkers, with at least 1 value greater than the 99th-percentile upper reference limit, concurrently with evidence of myocardial ischemia and corresponding clinical symptoms, electrocardiographic changes, or imaging evidence (1). Amo...

Aims/hypothesis: The pseudokinase tribbles homologue 3 (Drosophila) (TRIB3) negatively interferes with insulin-mediated phosphorylation and activation of v-akt murine thymoma viral oncogene homologue 1 (AKT1, also known as protein kinase B). Animal studies have shown that Trib3 expression was higher in the fasting state and in animal models of dia...

Copper has a role in antioxidant defense, lipid peroxidation, and mitochondrial function, and copper deficiency has been linked to atherogenic dyslipidemia. We aimed to investigate the potential role of copper availability in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Patients with NAFLD (n=124) were compared to patients with chr...

Adiponectin signalling attenuates insulin resistance (IR) and steatosis hepatis in animal models. As adiponectin receptor (ADIPOR)1 and ADIPOR2 are critical components in the adiponectin signalling cascade, we studied hepatic ADIPOR1/2 mRNA levels in humans and their relation to IR. We determined metabolic risk factors and levels of hepatic mRNA tr...

Relationship between APOE, GGCX and Calumenin genotypes and mean phenprocoumon weekly dose requirement

Relationship between APOE, GGCX and Calumenin genotypes and mean acenocoumarol weekly dose requirement

Iron overload may contribute to the pathogenesis of insulin resistance. We aimed to investigate the relationship among iron stores, liver transaminases and components of the metabolic syndrome in healthy teenagers in a cross-sectional study. We determined body mass index (BMI), waist-to-hip-ratio (WHR), blood pressure, liver ultrasound, serum lipid...

The variability in warfarin dose requirement is attributable to genetic and environmental factors. Acenocoumarol (AC) and phenprocoumon (PC) are coumarin derivates widely prescribed in European countries for the prevention and treatment of thromboembolic events. The aim of our study was to investigate the contribution of genes involved in the vitam...

HIV type-1 (HIV-1) genetic diversity poses a challenge for the development of diagnostic tests based on nucleic acid amplification, which can be overcome, at least in part, by targeting multiple genomic regions. The new Roche Diagnostics COBAS TaqMan (CTM) HIV-1 v2.0 assay uses multiplex real-time PCR detection of sequences in the long terminal rep...

Conjugated linoleic acid (CLA) isomers are dietary fatty acids that modulate gene expression in many cell types. We have previously reported that specifically trans-9,trans-11 (t9,t11)-CLA induces expression of genes involved in lipid metabolism of human macrophages. To elucidate the molecular mechanism underlying this transcriptional activation, w...

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedi...

Peroxisome proliferator-activated receptor-gamma co-activator-1 (PGC-1) alpha and -beta play pivotal roles in the regulation of intermediary metabolism. We have previously shown that PGC-1alpha-mediated upregulation of beta-cell sterol element binding protein (SREBP) gene expression impairs insulin secretion via increased transcription of uncouplin...

Primer sequences, annealing temperatures, and amplicon sizes of quantitative real-time PCR assays