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Publications (106)
The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in health and disease, detailed documentation of healthy metabolic responses is needed but still scarc...
Food intake triggers extensive changes in the blood metabolome. The kinetics of these changes depend on meal composition and on intrinsic, health-related characteristics of each individual, making the assessment of changes in the postprandial metabolome an opportunity to assess someone's metabolic status. To enable the usage of dietary challenges a...
Resistance training promotes metabolic health and stimulates muscle hypertrophy, but the precise routes by which resistance exercise (RE) conveys these health benefits are largely unknown.
Aim:
To investigate how acute RE affects human skeletal muscle metabolism.
Methods:
We collected vastus lateralis biopsies from six healthy male untrained vo...
Dried blood spots (DBS) are an alternative sampling method to blood plasma sampling. In contrast to blood plasma sampling, DBS are low-volume capillary blood samples obtained via pricking and collection on paper cards. DBS require less space and no cooling which is advantageous for exercise tests in the field. The aim of this project was to compare...
Resistance training promotes metabolic health and stimulates muscle hypertrophy, but the precise routes by which resistance exercise (RE) conveys these health benefits is largely unknown. Aim: To investigate how acute RE affects human skeletal muscle metabolism. Methods: We collected vastus lateralis biopsies from six healthy male untrained volunte...
INTRODUCTION: Embedding single-omics disease associations into the wider context of multi-level molecular changes in Alzheimer's disease (AD) remains one central challenge in AD research.
METHODS: Results from numerous AD-specific omics studies from AMP-AD, NIAGADS, and other initiatives were integrated into a comprehensive network resource and com...
Human metabolism is highly variable. At one end of the spectrum, defects of enzymes, transporters, and metabolic regulation result in metabolic diseases such as diabetes mellitus or inborn errors of metabolism. At the other end of the spectrum, favorable genetics and years of training combine to result in physiologically extreme forms of metabolism...
Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolite...
Background:
Exercise changes the concentrations of many metabolites, which are small molecules (< 1.5 kDa) metabolized by the reactions of human metabolism. In recent years, especially mass spectrometry-based metabolomics methods have allowed researchers to measure up to hundreds of metabolites in a single sample in a non-biased fashion. To summar...
Kit-based assays, such as AbsoluteIDQTM p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally-relevant information on t...
Kit-based assays, such as AbsoluteIDQ p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally relevant information on the...
Prolonged storage of biospecimen can lead to artificially altered metabolite concentrations and thus bias data analysis in metabolomics experiments. To elucidate the potential impact of long-term storage on the metabolite profile, a pooled human plasma sample was aliquoted and stored at 80 °C. During a time period of five years, 1012 of the aliquot...
Background/objectives:
Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD.
Subjects/methods:
In a populati...
Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Cu...
A critical question facing the field of metabolomics is whether data obtained from different centres can be effectively compared and combined. An important aspect of this is the inter-laboratory precision (reproducibility) of the analytical protocols used. We analysed human samples in six laboratories using different instrumentation but a common pr...
Objective:
Insulin-like Growth Factor (IGF-I) is known for its various physiological and severe pathophysiological effects on human metabolism, however underlying molecular mechanisms still remain unsolved. To reveal possible molecular mechanisms mediating these effects, for the first time we associated serum IGF-I levels with multi-fluid untarget...
Aims/hypothesis
Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures...
Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of A...
Usage of the agents within the class “ACE inhibitors”.
(PDF)
Characteristics of the population related to the intake of ACE inhibitors.
(PDF)
Metabolites measured in KORA F4.
(PDF)
Results for all analyzed ACE SNPs in KORA.
(XLS)
Boxplots for all analyzed ACE-SNPs in KORA.
(PDF)
Boxplots for ACE-SNP rs4329 in TwinsUK.
(PDF)
Aims: Lactation for > 3 months in women with gestational diabetes is associated with a considerably reduced long-term risk for type 2 diabetes that persists for up to 15 years postpartum. However, the underlying protective mechanisms are unknown. We examined whether lactation for > 3 months is associated with altered metabolomic signatures postpart...
Small molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach...
Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blo...
Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin.
We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on...
Metabolites are small molecules involved in cellular metabolism, which can be detected in biological samples using metabolomic techniques. Here we present the results of genome-wide association and meta-analyses for variation in the blood serum levels of 129 metabolites as measured by the Biocrates metabolomic platform. In a discovery sample of 7,4...
Advances in the "omics" field bring about the need for a high number of good quality samples. Many omics studies take advantage of biobanked samples to meet this need. Most of the laboratory errors occur in the pre-analytical phase. Therefore evidence-based standard operating procedures for the pre-analytical phase as well as markers to distinguish...
High-throughput screening techniques that analyze the metabolic endpoints of biological processes can identify the contributions of genetic predisposition and environmental factors to the development of common diseases. Studies applying controlled physiological challenges can reveal dysregulation in metabolic responses that may be predictive for or...
The measurement of metabolites during intravenous or nutritional challenges may improve the identification of novel metabolic signatures which are not detectable in the fasting state. Here, we comprehensively characterized the plasma metabolomics response to five defined challenge tests and explored their use to identify interactions with the FTO r...
The mechanism of antihypertensive and lipid-lowering drugs on the human organism is still not fully understood. New insights on the drugs’ action can be provided by a metabolomics-driven approach, which offers a detailed view of the physiological state of an organism. Here, we report a metabolome-wide association study with 295 metabolites in human...
Aim: Metabolites can be very sensitive markers for the evaluation of drug efficiency and safety. We analyzed changes in the metabolome of adolescent pre-diabetic pigs expressing a dominant negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn) after treatment with the GLP-1 receptor agonist liraglutide using a targeted metabolomics...
Emerging technologies based on mass spectrometry or nuclear magnetic resonance enable the monitoring of hundreds of small metabolites from tissues or body fluids. Profiling of metabolites can help elucidate causal pathways linking established genetic variants to known disease risk factors such as blood lipid traits.
We applied statistical methodolo...
Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D).
We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia.
We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for w...
Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant.
Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subje...
Previously, we reported strong influences of genetic variants on metabolic phenotypes, some of them with clinical relevance. Here we hypothesize that DNA methylation may have an important and potentially independent effect on human metabolism. To test this hypothesis we conducted what is to the best of our knowledge the first epigenome-wide associa...
Background
Serum metabolites are associated cross-sectionally with kidney function in population-based studies.
Methods
Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic...
Nutrition plays an important role in human metabolism and health. Metabolomics is a promising tool for clinical, genetic and nutritional studies. A key question is to what extent metabolomic profiles reflect nutritional patterns in an epidemiological setting. We assessed the relationship between metabolomic profiles and nutritional intake in women...
Background:
Individuals with negative affectivity who are inhibited in social situations are characterized as distressed, or Type D, and have an increased risk of cardiovascular disease (CVD). The underlying biomechanisms that link this psychological affect to a pathological state are not well understood. This study applied a metabolomic approach...
Systematic classifications for 106 unknown metabolites.
(XLS)
Detailed GGM modularity analysis results.
(PDF)
Assessment of the majority voting classification approach.
(PDF)
ZIP archive containing Excel sheets and .graphml files for the GGM and GWAS results, as well as detailed pathway annotations.
(ZIP)
GGM sub-network with bilirubin variants.
(PDF)
Supporting experimental data and description of the unknown identification scenarios CARNITINE, BILIRUBIN, and ASCORBATE.
(PDF)
Objective:
The human serum metabolite profile is reflective of metabolic processes, including pathophysiological changes characteristic of diseases. Therefore, investigation of serum metabolite concentrations in obese children might give new insights into biological mechanisms associated with childhood obesity.
Methods:
Serum samples of 80 obese...
Recent genome-wide association studies (GWAS) with metabolomics data linked genetic variation in the human genome to differences in individual metabolite levels. A strong relevance of this metabolic individuality for biomedical and pharmaceutical research has been reported. However, a considerable amount of the molecules currently quantified by mod...
Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We rep...
To characterise the influence of the fat free mass on the metabolite profile in serum samples from participants of the population-based KORA (Cooperative Health Research in the Region of Augsburg) S4 study.
Analyses were based on metabolite profile from 965 participants of the S4 and 890 weight-stable subjects of its seven-year follow-up study (KOR...
Full biochemical names, abbreviation, mean ± standard deviation of all metabolite concentrations measured in µmol/l with the Biocrates Absolute
IDQ
kits p150 (KORA F4, n = 890) and p180 (KORA S4, n = 965).
(DOC)
Diabetes is generally diagnosed too late. Therefore, biomarkers indicating early stages of β-cell dysfunction and mass reduction would facilitate timely counteraction. Transgenic pigs expressing a dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPR(dn)) reveal progressive deterioration of glucose control and reduction of β...
Metabolites such as creatinine and urea are established kidney function markers. High-throughput metabolomic studies have not been reported in large general population samples spanning normal kidney function and chronic kidney disease (CKD).
Cross-sectional observational studies of the general population.
2 independent samples: KORA F4 (discovery s...
Metabolic challenge protocols, such as the oral glucose tolerance test, can uncover early alterations in metabolism preceding chronic diseases. Nevertheless, most metabolomics data accessible today reflect the fasting state. To analyze the dynamics of the human metabolome in response to environmental stimuli, we submitted 15 young healthy male volu...
Adverse levels of lipoproteins are highly heritable and constitute risk factors for cardiovascular outcomes. Hitherto, genome-wide association studies revealed 95 lipid-associated loci. However, due to the small effect sizes of these associations large sample numbers (>100 000 samples) were needed. Here we show that analyzing more refined lipid phe...