Nils Helge Schebb

Nils Helge Schebb
Bergische Universität Wuppertal | Uni-Wuppertal, BUW · Department of Mathematics and Natural Sciences

PhD, Food Chemist and Toxicologist (DGPT, ERT)

About

167
Publications
13,920
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3,225
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Introduction
Our research focuses on the investigation of biological activities employing instrumental analytical methods. By providing quantitative data about the activity and concentration of compounds we seek to improve the systematic/molecular understanding of their protective as well as toxicological effects. The current work focusses on: Metabolomics- Investigation of the impact of food ingredients and contaminants on endogenous pathways of inflammation for more information: schebb-web.de
Additional affiliations
July 2014 - August 2016
Bergische Universität Wuppertal
Position
  • W3 Professor (Full, interim head of department)
March 2009 - May 2011
University of California, Davis
Position
  • PostDoc Position
September 2004 - January 2006
Karlsruhe University of Applied Sciences
Position
  • Grad Student

Publications

Publications (167)
Article
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Supplementing long-chain omega-3 polyunsaturated fatty acids (n3-PUFA) improves health. We characterized the pattern of total and non-esterified oxylipins and fatty acids in n3 supplements made of fish, krill, or micro-algae oil by LC-MS. All supplements contained the declared amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); ho...
Preprint
Full-text available
Background Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Integratively phenotyping the molecular pathways involved in MetS would help to deeply characterize its pathophysiology and to better stratify the risk of cardiometabolic diseases. Oxylipins are a superfamilly of lipid mediator...
Article
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Formation of specialized pro-resolving lipid mediators (SPMs) such as lipoxins or resolvins usually involves arachidonic acid 5-lipoxygenase (5-LO, ALOX5) and different types of arachidonic acid 12- and 15-lipoxygenating paralogues (15-LO1, ALOX15; 15-LO2, ALOX15B; 12-LO, ALOX12). Typically, SPMs are thought to be formed via consecutive steps of ox...
Article
Epoxy- and hydroxy-fatty acids are physiologically active lipid mediators which are formed from arachidonic acid and other fatty acids by cytochrome P450 monooxygenase (CYP) catalytic activity. In this study, we investigated the structure-activity relationship of the inhibition of fatty acid oxidizing CYP by flavonoids. A sum of 65 naturally occurr...
Article
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Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (C...
Article
Neutrophils are key players in inflammation initiation and resolution. Little attention has been paid to the detailed biosynthesis of specialized pro-resolving mediators (SPM) in these cells. We investigated SPM formation in human polymorphonuclear leukocytes (PMNL), in broken PMNL preparations and recombinant human 5-lipoxygenase (5-LO) supplement...
Article
Full-text available
Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (Alox5-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid o...
Article
Full-text available
The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in respons...
Article
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Fetal bovine serum (FBS) has been used as a universal supplement in cell culture for more than six decades. This includes the investigation of lipid and lipid mediator formation and biology. Little is known about the (polyunsaturated) fatty acid composition and their oxidation products in FBS. Therefore, we analyzed six different FBS purchased from...
Article
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Analysis of fatty acids (FA) in food and biological samples such as blood is indispensable in modern life sciences. We developed a rapid, sensitive and comprehensive method for the quantification of 41 saturated and unsaturated fatty acids by means of LC-MS. Optimized chromatographic separation of isobaric analytes was carried out on a C8 reversed...
Article
The use of insects as food and feed is gaining more attention for ecological and ethical reasons. Despite the high tolerance of edible yellow mealworm (Tenebrio molitor) larvae to aflatoxin B1 (AFB1), the metabolic fate of the toxin along with its toxic potential in the insect is uncertain. The present study aimed at investigating the AFB1 mass bal...
Article
Full-text available
An increased omega‐3 polyunsaturated fatty acid (n‐3 PUFA) tissue status can lead to a significant formation of anti‐inflammatory lipid mediators and effective reduction in inflammation and tissue injury in murine colitis. Arachidonic acid lipoxygenases (ALOX) have been implicated in the pathogenesis of inflammatory bowel disease as well as in the...
Article
Full-text available
This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 we...
Article
Objective Cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) is an important lipid mediator in colorectal carcinoma (CRC) pathogenesis. Other lipid mediators derived from lipoxygenases (LOX) have also been implicated in neoplastic processes in the colon. In this study we aimed to characterize lipid mediators, so called oxylipins, in human colon a...
Article
Full-text available
Macrophages acquire anti-inflammatory and proresolving functions to facilitate resolution of inflammation and promote tissue repair. While alternatively activated macrophages (AAMs), also referred to as M2 macrophages, polarized by type 2 (Th2) cytokines IL-4 or IL-13 contribute to the suppression of inflammatory responses and play a pivotal role i...
Article
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The intake of long-chain n3-polyunsaturated fatty acids (PUFA), which are associated with beneficial health effects, is low in the Western diet, while the portion of dietary n6-PUFA and hence the n6/n3-PUFA ratio is high. Strategies to improve the n3-PUFA status are n3-PUFA supplementation and/or lowering n6-PUFA intake. In the present study, mice...
Article
Full-text available
The important role of inducible cyclooxygenase‐2 (COX‐2) in inflammation‐related diseases and cancer necessitates analytical tools that enable thorough understanding of its modulation. Analysis of a comprehensive pattern of oxylipins provides detailed information about changes in enzyme activities. In order to simultaneously monitor the gene expres...
Article
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We introduce STAMPS, a pathway centric web service for the development of targeted proteomics assays. STAMPS guides the user by providing several intuitive interfaces for a rapid and simplified method design. Applying our curated framework to signaling and metabolic pathways, we reduced the average assay development time by a factor of ~150 and rev...
Article
Full-text available
Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are rarely comparable, which increas...
Article
Rationale - Acute kidney injury (AKI) frequently complicates major surgery and can be associated with hypertension and progress to chronic kidney disease (CKD), but reports on blood pressure normalization in AKI are conflicting. Objective - We investigated the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril, and the soluble...
Article
The products of the cytochrome P450 monooxygenase (CYP)-catalyzed oxidation of arachidonic acid (AA), i.e. epoxy- and hydroxy-fatty acids, play a crucial role in the homeostasis of several physiological processes. In a liver microsome-based multi-enzyme assay using AA as natural substrate, we investigated how polyphenols inhibit different oxylipin-...
Article
Lipoxygenases (ALOX) are lipid peroxidizing enzymes that catalyze the biosynthesis of pro- and anti-inflammatory lipid mediators and have been implicated in (patho-)physiological processes. In humans, six functional ALOX isoforms exist and their arachidonic acid oxygenation products have been characterized. Products include leukotrienes and lipoxin...
Article
Full-text available
Eicosanoids and other oxylipins play an important role in mediating inflammation as well as other biological processes. For the investigation of their biological role(s), comprehensive analytical methods are necessary, which are able to provide reliable identification and quantification of these compounds in biological matrices. Using charge-switch...
Article
Objectives Neuroinflammation contributes to brain-aging which may be mitigated by anti-inflammatory oxylipins. Based on our previous findings that a 6% walnut-enriched diet alone, and additional physical activity (PA), enhanced cognition in 18 months old NMRI, we now investigated the effects of this diet on oxylipin- and inflammatory marker levels...
Article
Oxidized unsaturated fatty acids – i.e. eicosanoids and other oxylipins – can act as lipid mediators which are involved in the regulation of numerous physiological functions such as inflammation. They have raised strong interest in clinical lipidomics to understand their role in diseases and their use as biomarkers. However, the results of clinical...
Article
Objective This study aimed to assess polyunsaturated fatty acid (PUFA) status and association with systemic inflammation and fish consumption in systemic lupus erythematosus (SLE). Methods Parameters of PUFA status including the proportion of omega-6 and -3 fatty acids in highly unsaturated fatty acids (omega-6%, omega-3%), essential fatty acids l...
Article
Full-text available
Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of epoxides derived from long-chain polyunsaturat...
Article
Macrophage polarization switches during the course of inflammation along with the lipid mediators released. We investigated the lipid mediator formation in human monocyte-derived macrophages during in vitro differentiation and pathogen stimulation. For this, peripheral blood monocytes were differentiated into M1 (CSF-2/IFNγ) or M2 (CSF-1/IL-4) macr...
Article
Full-text available
Quantitative analysis of oxylipins in blood samples is of increasing interest in clinical studies. However, storage after sampling and transport of blood might induce artificial changes in the apparent oxylipin profile due to ex-vivo formation/degradation by autoxidation or enzymatic activity. In the present study we investigated the stability of f...
Article
Full-text available
Although early detection and treatment of colorectal cancer (CRC) have improved, it remains a significant health-care problem with high morbidity and mortality. Data indicate that long-term intake of low-dose aspirin reduces the risk of CRC; however, the mechanisms underlying this chemopreventive effect are still unclear. Different mouse models for...
Article
A major part of oxygenated metabolites of polyunsaturated fatty acids - i.e. eicosanoids and other oxylipins - in biological samples occurs in the esterified form. Yet, their biological role is only poorly understood. For quantification of esterified oxylipins in biological samples current protocols mostly apply alkaline hydrolysis with or without...
Article
Background: Acute kidney injury (AKI) is an important complication after major surgery and solid organ transplantation. Here, we present a dietary omega-3 polyunsaturated fatty acid (n3-PUFA) supplementation study to investigate whether pre-treatment can reduce ischemia induced AKI in mice. Methods: Male 12-14 week old C57BL/6 J mice received a...
Article
Aims: Most mammalian genomes involve several genes encoding for functionally distinct ALOX-isoforms. Pro-inflammatory leukotrienes are formed via the ALOX5 pathway but 12/15-lipoxygenating ALOX-isoforms have been implicated in the biosynthesis of pro-resolving mediators. In vitro mutagenesis of the triad determinants abolished the leukotriene synt...
Article
Full-text available
The omega-3 (n3) polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with health benefits. The primary dietary source of EPA and DHA is seafood. Alpha-linoleic acid (ALA) has not been shown to be a good source for EPA and DHA; however, stearidonic acid (SDA)—which is naturally contained in ec...
Article
Full-text available
Background Somatic migration of Toxocara canis- and T. cati-larvae in humans may cause neurotoxocarosis (NT) when larvae accumulate and persist in the central nervous system (CNS). Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis; however, detailed data on involvement of bioactive lipid mediators, e.g. oxylipins o...
Article
Amaranth is regarded as a new “super-vegetable” in western countries, albeit it is consumed for centuries in Africa and Asia. In addition to common carotenoids, flavonoids and polyphenols, caffeoylisocitric acid has been described as amaranth type-specific secondary metabolite. Remarkably, nothing is known on biological effects of this specific pol...
Article
Full-text available
Objectives We investigated changes of renal perfusion after topical and oral diclofenac administration in healthy volunteers using functional magnetic resonance imaging (MRI) with arterial spin labelling (ASL). Methods Twenty‐four healthy human participants (21–51 years) underwent 1.5T MRI before and 1 h after a single oral dose of diclofenac (50...
Article
Oxylipins, including the well-known eicosanoids, are potent lipid mediators involved in numerous physiological and pathological processes. Therefore, their quantitative profiling has gained a lot of attention during the last years notably in the active field of health biomarker discovery. Oxylipins include hundreds of structurally and stereochemica...
Article
The intake of food polyphenols is associated with beneficial impacts on health. Besides anti-oxidative effects, anti-inflammatory properties have been suggested as molecular modes of action, which may result from modulations of the arachidonic acid (AA) cascade. Here, we investigated the effects of a library of food polyphenols on 5-lipoxygenase (5...
Article
In mammals, epoxy-polyunsaturated fatty acids (epoxy-PUFA) are enzymatically formed from naturally occurring all-cis PUFA by cytochrome P450 monooxygenases leading to the generation of cis-epoxy-PUFA (mixture of R,S- and S,R-enantiomers). In addition, also non-enzymatic chemical peroxidation gives rise to epoxy-PUFA leading to both, cis- and trans-...
Article
Full-text available
The cardioprotective and anti-inflammatory effects of long chain omega-3 polyunsaturated fatty acids (n3 PUFA) are believed to be partly mediated by their oxygenated metabolites (oxylipins). In the last two decades interest in a novel group of autacoids termed specialized pro-resolving mediators (SPMs) increased. These are actively involved in the...
Article
Full-text available
Lipoprotein apheresis reliably reduces low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). Besides lowering lipoproteins and triglycerides, apheresis also decreases levels of essential omega-6 and omega-3 polyunsaturated fatty acids (n-6...
Article
Quantitative analysis of oxylipins by means of chromatography/mass spectrometry is based on (external) calibration with standard compounds. Therefore, the quality of analytical standards is of fundamental importance for accurate results. Recently launched certified standards with an assured concentration within a narrow range are useful tools to ve...
Article
Background: The health effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) are partly mediated by their oxidized metabolites, i.e., eicosanoids and other oxylipins. Some intervention studies have demonstrated that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase systemic concentrations of n-3 PUFA-derived oxyli...
Article
Full-text available
Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophage functions. Among these strategies, Leishmania as a source of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of poly...
Article
Full-text available
Introduction: Several eicosanoids and other oxylipins are important lipid mediators. Reliable quantification in plasma is important to assess the state of disease, action of drugs and the biology of oxylipins. In order to monitor biological changes, low background variability of oxylipin concentrations in biological samples is essential for a prope...
Research
Full-text available
Meeting about bioactive lipids. Abstract submission: Dead-line prolongation until June18th, 2018 https://workshop-lipid.eu//index.php?cat=Abstract
Article
Characterizations of the multiple mechanisms determining biological aging are required to better understand the etiology and identify early biomarkers of sarcopenia. Oxylipins refer to a large family of signaling lipids involved in the regulation of various biological processes that become dysregulated during aging. To investigate whether comprehen...
Article
Full-text available
There is a debate about the optimal dietary ratio of the parent n6 fatty acid linoleic acid (LA) and n3 fatty acid alpha-linolenic acid (ALA) to promote an efficient conversion of ALA to EPA and DHA, which have implications for human health. The aim of the present study was to compare the effects of a low-LA/high-ALA (loLA/hiALA) diet with a high-L...
Article
Full-text available
The essential omega-3 fatty acid alpha-linolenic acid (ALA, 18:3n3) can be converted into EPA and DHA. The aim of the present study was to determine the effect of a high-ALA...
Article
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Eicosanoids, including prostaglandins and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppressi...
Article
Full-text available
Omega-6 polyunsaturated fatty acid (n-6 PUFA) is the predominant polyunsaturated fatty acid (PUFA), especially in Western diet. A high omega-6/omega-3 ratio in Western diets is implicated in the development of cardiovascular diseases and inflammatory processes. Studies in animal models and in humans have demonstrated beneficial effects of omega-3 P...
Article
Misregulation of oxidative and antioxidative processes in the organism – oxidative stress – contributes to the pathogenesis of different diseases, e.g. inflammatory or neurodegenerative diseases. Oxidative stress leads to autoxidation of polyunsaturated fatty acids giving rise to prostaglandin-like isoprostanes (IsoP) and isofurans (IsoF). On the o...