Gerhard Liebisch

University Hospital Regensburg | Uni Regensburg · Klinische Chemie und Laboratoriumsmedizin

Nature provides an enormous diversity of lipid molecules that originate from various pathways. To gain insight into the metabolism and dynamics of lipid species, the application of stable isotope-labeled tracers combined with mass spectrometric analysis represents a perfect tool. This review provides an overview of strategies to track fatty acid, g...

Compensation of matrix effects is the main obstacle to achieve accurate quantification in LC-MS/MS. Therefore, quantitative LC-MS/MS typically relies on addition of internal standards (ISs). Here, we present a systematic comparison of ISs from a routine LC-MS/MS method for bile acid (BA) analysis with a focus on tauro-conjugated. Both human serum b...

A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerop...

The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, compa...

A key element of successful lipidomics analysis is a sufficient extraction of lipid molecules typically by two-phase systems such as chloroform-based Bligh and Dyer (B&D). However, numerous metabolomics and lipidomics studies today apply easy to use one-phase extractions. In this work, quantitative flow injection analysis high-resolution mass spect...

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic immune-mediated pathology associated with the dysregulation of lipid metabolism. The administration of nervonic acid, a very long-chain fatty acid, has been shown to improve colonic inflammation in a mouse model of colitis. Our study aimed to quantify fecal levels of nervonic acid...

Interest in bile acids (BAs) is growing due to their emerging role as signaling molecules and their association with various diseases such as colon cancer and metabolic syndrome. Analyzing BAs requires chromatographic separation of isomers, often with long run times, which hinders BA analysis in large studies. Here, we present a high-throughput met...

Sphingosine 1-phosphate (S1P) is a lysosphingolipid with anti-atherogenic properties, but mechanisms underlying its effects remain unclear. We here investigated atherosclerosis development in cholesterol-rich diet-fed LDL receptor-deficient mice with high or low overexpression levels of S1P receptor type 1 (S1P1) in macrophages. S1P1-overexpressing...

Bile acids (BA) are supposed to cause metabolic alterations after bariatric surgery (BS). Here we report the longitudinal dynamics of the human BA metabolome by LC–MS/MS after BS versus low calory diet (LCD) in two obesity cohorts over 12 months. Rapid and persistent oscillations of 23 BA subspecies could be identified with highly specific patterns...

In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as w...

Background Long non-coding RNAs (lncRNAs) can perform tasks of key relevance in fat cells, contributing, when defective, to the burden of obesity and its sequelae. Here, scrutiny of adipose tissue transcriptomes before and after bariatric surgery (GSE53378) granted identification of 496 lncRNAs linked to the obese phenotype. Only expression of linc...

Cold-induced lipolysis is widely studied as a potential therapeutic strategy to combat metabolic disease, but its effect on lipid homeostasis in humans remains largely unclear. Blood plasma comprises an enormous repertoire in lipids allowing insights into whole body lipid homeostasis. So far, reported results originate from studies carried out with...

Aim: The gut microbiota is implicated in the development of intestinal tumors. Furthermore, Western diet is a risk factor for colorectal cancer and induces alterations in both the microbiota and bile acid metabolism. Therefore, we aimed to investigate the causal role of Western diet-induced changes in the microbiota and secondary bile acid producti...

Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the loca...

Citation: Birner, C.; Mester, P.; Liebisch, G.; Höring, M.; Schmid, S.; Müller, M.; Pavel, V.; Buechler, C. These authors contributed equally to this work. Abstract: Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in...

Increasing energy expenditure in brown adipose (BAT) tissue by cold-induced lipolysis is discussed as a potential strategy to counteract imbalanced lipid homeostasis caused through unhealthy lifestyle and cardiometabolic disease. Yet, it is largely unclear how liberated fatty acids (FA) are metabolized. We investigated the liver and BAT lipidome of...

The (patho)physiological function of the sphingolipids ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC) in articular joints during osteoarthritis (OA) is largely unknown. Therefore, we investigated the influence of these lipids on protein expression by fibroblast-like synoviocytes (FLSs) from OA knees...

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associat...

Citation: Mester, P.; Amend, P.; Schmid, S.; Wenzel, J.J.; Höring, M.; Liebisch, G.; Krautbauer, S.; Müller, M.; Buechler, C.; Pavel, V. Proprotein These authors contributed equally to this work. Abstract: SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the...

FATP4 was thought to mediate intestinal lipid absorption which was disputed by a study using keratinocyte-Fatp4-rescued Fatp4 -/- mice. These knockouts when fed with a western diet showed elevated intestinal triglyceride (TG) and fatty-acid levels. To investigate a possible role of FATP4 on intestinal lipid processing, ent-Fatp4 (KO) mice were gene...

Lipid composition is conserved within sub-cellular compartments to maintain cell function. Lipidomic analyses of liver, muscle, white and brown adipose tissue (BAT) mitochondria revealed substantial differences in their glycerophospholipid (GPL) and free cholesterol (FC) contents. The GPL to FC ratio was 50-fold higher in brown than white adipose t...

The spreading awareness of the health benefits associated with the consumption of plant-based foods is fueling the market of innovative vegetable products, including microgreens, recognized as a promising source of bioactive compounds. To evaluate the potential of oleaginous plant microgreens as a source of bioactive fatty acids, gas chromatography...

Soluble CD163 (sCD163) is a selective marker of macrophages whose circulating levels have been found to be induced in patients with active inflammatory bowel disease (IBD). Urinary proteins are emerging as non-invasive diagnostic biomarkers, and here, sCD163 levels were measured in the urine of 18 controls and 63 patients with IBD by enzyme-linked...

Ferroptosis is a cell death pathway that can be promoted by peroxidizable polyunsaturated fatty acids in cancer cells. Here, we investigated the mechanisms underlying the toxicity of punicic acid (PunA), an isomer of conjugated linolenic acids (CLnAs) bearing three conjugated double bonds highly prone to peroxidation, on prostate cancer (PCa) cells...

Barth Syndrome (BTHS) is a rare X-linked disease, characterized clinically by cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the phospholipid acyltransferase tafazzin (Gene: TAFAZZIN, TAZ). Tafazzin catalyzes the final step in the remodeling of cardiolipin (CL), a glycerophospholipid located i...

Background A consistent finding in inflammatory bowel disease (IBD) is an altered composition of fecal bile acids, with an increase in primary bile acids and a decrease in secondary bile acids. It is less clear, whether fecal bile acids could prove to be biomarkers for IBD diagnosis and disease activity. The study aimed to determine correlations be...

Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the...

The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in...

Background Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid speci...

The induction of endoplasmic reticulum unfolded protein responses (UPR ER ) contributes to cancer development and progression. We recently linked microbiota-related triggers to the tumor-promoting role of signal transducer activating transcription factor 6 (ATF6) in the colon. Here we substantiate the clinical relevance of ATF6 and related bacteria...

Lipid analysis gained significant importance due to the enormous range of lipid functions, e.g., energy storage, signaling, or structural components. Whole lipidomes can be quantitatively studied in-depth thanks to recent analytical advancements. However, the systematic comparison of thousands of distinct lipidomes remains challenging. We introduce...

Background: Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this p...

A high phosphorus intake has been associated with various metabolic disorders, including chronic kidney disease, cardiovascular disease, and osteoporosis. Recent studies have demonstrated the effects of dietary phosphorus on lipid and glucose metabolism. This study investigated the impact of a high-phosphorus diet on mouse skeletal muscle lipid com...

Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol...

Background and Purpose Fibroblast growth factors and receptors (FGFR) have been shown to modulate inflammation and neurodegeneration in multiple sclerosis (MS). The selective FGFR inhibitor infigratinib has been shown to be effective in cancer models. Here, we investigate the effects of infigratinib on prevention and suppression of first clinical e...

Background Gut microbiome studies are helping to understand the mechanisms by which Clostridium difficile infection (CDI) and its recurrences are favoured, as well as recovery from it through different types of treatment. In addition to the impact on microbiome composition and given the metabolic changes occurring at the gut level during CDI, our i...

Over the past decades, a remarkable number of scientific studies supported the correlation between an adequate dietary intake of phytosterols (PS) and the reduced risk of cardiovascular diseases. PS are known to inhibit the intestinal absorption of cholesterol, thus promoting the reduction of the low-density lipoproteins (LDL) amount in the bloodst...

Synovial fluid (SF) from human knee joints with osteoarthritis (OA) has elevated levels of lysophosphatidylcholine (LPC) species, but their functional role is not well understood. This in vitro study was designed to test the hypothesis that various LPCs found elevated in OA SF and their metabolites, lysophosphatidic acids (LPAs), modulate the abund...

The neurobiological underpinnings of major depressive disorder (MDD) remain still elusive. Meanwhile, mitochondria and energy metabolism turn into focus as relevant pathomechanisms of MDD. To gain further insight on the role of mitochondria function in MDD, in the present work, we examined the functional cellular and mitochondrial properties in cel...

Background: The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression, and high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be inv...

Fibroblast growth factors (FGFs) are key regulators of the remarkable regenerative capacity of the liver. Mice lacking FGF receptors 1 and 2 (Fgfr1 and Fgfr2) in hepatocytes are hypersensitive to cytotoxic injury during liver regeneration. Using these mice as a model for impaired liver regeneration, we identified a critical role for the ubiquitin l...

Replacement of soybean oil by insect fat from Hermetia illucens (HI) has been reported to increase the proportions of saturated fatty acids (SFA) and decrease those of polyunsaturated fatty acids (PUFA) in total lipids of breast and thigh meat in broilers. Since the susceptibility of meat to oxidation is strongly dependent on its PUFA content, the...

Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was compl...

Background: Genetic variants at the TRIB1 gene locus are strongly associated with plasma lipid traits and the risk of coronary artery disease in humans. Here, we analyzed the consequences of Trib1 deficiency on lipid metabolism and atherosclerotic lesion formation in atherosclerosis-susceptible Ldlr-/-. Methods: Trib1-/- mice were crossed onto t...

Lipids play a central role in platelet physiology. Changes in the lipidome have already been described for basal and activated platelets. However, quantitative lipidomic data of platelet activation, including the released complex lipids, are unavailable. Here we describe an easy-to-use protocol based on flow-injection mass spectrometry for the quan...

Reliability, robustness, and inter-laboratory comparability of quantitative measurements is critical for clinical lipidomics studies. Lipids' different ex vivo stability in blood bears the risk of misinterpretation of data. Clear recommendations for the process of blood sample collection are required. We studied by UHPLC-high-resolution mass spectr...

Intake of Western diet stimulates bile acid (BA) production and their conversion to secondary BAs by 7α-dehydroxylating (7αDH+) bacteria in the colon. Increased levels of 7αDH+ bacteria and the secondary BA deoxycholic acid (DCA) have been associated with sporadic colorectal cancer (CRC). However, causal proof of their tumour-promoting effects unde...

Abstract Background In contrast to protein-rich insect meal, the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still limited. In view of this, the present study aimed to comprehensively investigate the effect of partial (50%) and complete re...

There is general consent that with decreasing bone mineral density the amount of marrow adipose tissue increases. While image-based techniques, claim an increase in saturated fatty acids responsible for this effect, this study shows an increase in both saturated and unsaturated fatty acids in the bone marrow. Using fatty acid methyl ester gas chrom...

Background: Microbiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD. Methods: We performed a cross-sectional study...

Direct infusion, often referred to as shotgun lipidomics, is one of the main workflows in lipidomics. In this chapter, we discuss the complexity of crude lipid extracts, potential pitfalls, and how to resolve isobars, including Type‐II overlap. Main steps of direct infusion‐based workflows are discussed comprising sample preparation, sample infusio...

Objectives: Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease that can range from hepatic steatosis to non-alcoholic steatohepatitis (NASH), which can lead to fibrosis and cirrhosis. Recently, ketogenic diet (KD), a low carbohydrate diet, gained popularity as a weight-loss approach, although it has been repo...

Visceral adiposity is strongly associated with liver steatosis, which predisposes to the development of non-alcoholic steatohepatitis (NASH). Mice with loss of the molecular adapter protein beta-2 syntrophin (SNTB2) have greatly reduced intra-abdominal fat mass. Hepatic expression of proteins with a role in fatty acid metabolism such as fatty acid...

Background & aims: Hepatocyte growth and proliferation depends on membrane phospholipid biosynthesis. Short chain fatty acids (SCFA) generated by bacterial fermentation, delivered through the gut-liver axis, significantly contribute to lipid biosynthesis. We therefore hypothesized that dysbiotic insults like antibiotics treatment not only affect g...

Bile acids are essential for food digestion and nutrient absorption, but also act as signalling molecules involved in hepatobiliary diseases, gastrointestinal disorders and carcinogenesis. While many studies have focused on the genetic determinants of blood metabolites, research focusing specifically on genetic regulation of bile acids in the gener...

Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays pro...

Background Thyroid hormone responsive protein (THRSP) is a lipogenic nuclear protein that is highly expressed in murine adipose tissue, but its role in humans remains unknown. Methods We characterized the insulin regulation of THRSP in vivo in human adipose tissue biopsies and in vitro in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes . To this...

Background Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. Methods The study included the ser...

Mass spectrometry (MS)-based lipidomics has revolutionized lipid research. However, numerous studies are reporting poor quality lipidomics data with misidentification and inaccurate/inappropriate quantification of lipid molecules. Therefore, we have launched the Lipidomics Standards Initiative (LSI; https://lipidomicstandards.org), an open-access w...

The mammalian lipidome represents a complex mixture of lipid molecules. Although major lipid classes are quantifiable by direct infusion mass spectrometry in crude lipid extracts, minor lipid species typically require LC-separation coupled to tandem mass spectrometry (LC-MS/MS) to increase sensitivity and specificity. Matrix effects are a key obsta...

Hepatitis C virus (HCV) infection affects ceramide metabolism, and, here, we have evaluated associations of eight serum ceramide species with viral load, viral genotype, and disease markers in 178 patients with chronic HCV. In this cohort, ceramide d18:1;O2/16:0 was higher in the serum of the 20 diabetic patients compared to the patients without th...

Background & Aims Hepatocyte growth and proliferation is dependent on the synthesis of membrane phospholipids. Lipid synthesis, in turn, requires short chain fatty acids (SCFA) generated by bacterial fermentation, delivered through the gut- liver axis. We therefore hypothesized that dysbiotic insults like antibiotics treatment not only negatively a...

Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin is...

Golgi membrane protein 1 (GOLM1) is a Golgi-resident type 2 transmembrane protein known to be overexpressed in several cancers, including hepatocellular carcinoma (HCC), as well as in viral infections. However, the role of GOLM1 in lipid metabolism remains enigmatic. In this study, we employed siRNA-mediated GOLM1 depletion in Huh-7 HCC cells to st...

The rapid increase in lipidomic data has triggered a community-based movement to develop guidelines and minimum requirements for generating, reporting and publishing lipidomic data. The creation of a dynamic checklist summarizing key details of lipidomic analyses using a common language has the potential to harmonize the field by improving both tra...

The content of polyunsaturated fatty acids (PUFA) in complex lipids essentially influences their physicochemical properties and has been linked to health and disease. To investigate the incorporation of dietary PUFA in the human plasma lipidome, we quantified glycerophospholipids (GPL), sphingolipids, and sterols using electrospray ionization coupl...