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  1. Article ; Online: Metabolomics in human SGBS cells as new approach method for studying adipogenic effects: Analysis of the effects of DINCH and MINCH on central carbon metabolism.

    Goerdeler, Cornelius / Engelmann, Beatrice / Aldehoff, Alix Sarah / Schaffert, Alexandra / Blüher, Matthias / Heiker, John T / Wabitsch, Martin / Schubert, Kristin / Rolle-Kampczyk, Ulrike / von Bergen, Martin

    Environmental research

    2024  Volume 252, Issue Pt 2, Page(s) 118847

    Abstract: Growing evidence suggests that exposure to certain metabolism-disrupting chemicals (MDCs), such as the phthalate plasticizer DEHP, might promote obesity in humans, contributing to the spread of this global health problem. Due to the restriction on the ... ...

    Abstract Growing evidence suggests that exposure to certain metabolism-disrupting chemicals (MDCs), such as the phthalate plasticizer DEHP, might promote obesity in humans, contributing to the spread of this global health problem. Due to the restriction on the use of phthalates, there has been a shift to safer declared substitutes, including the plasticizer diisononyl-cyclohexane-1,2-dicarboxylate (DINCH). Notwithstanding, recent studies suggest that the primary metabolite monoisononyl-cyclohexane-1,2-dicarboxylic acid ester (MINCH), induces differentiation of human adipocytes and affects enzyme levels of key metabolic pathways. Given the lack of methods for assessing metabolism-disrupting effects of chemicals on adipose tissue, we used metabolomics to analyze human SGSB cells exposed to DINCH or MINCH. Concentration analysis of DINCH and MINCH revealed that uptake of MINCH in preadipocytes was associated with increased lipid accumulation during adipogenesis. Although we also observed intracellular uptake for DINCH, the solubility of DINCH in cell culture medium was limited, hampering the analysis of possible effects in the μM concentration range. Metabolomics revealed that MINCH induces lipid accumulation similar to peroxisome proliferator-activated receptor gamma (PPARG)-agonist rosiglitazone through upregulation of the pyruvate cycle, which was recently identified as a key driver of de novo lipogenesis. Analysis of the metabolome in the presence of the PPARG-inhibitor GW9662 indicated that the effect of MINCH on metabolism was mediated at least partly by a PPARG-independent mechanism. However, all effects of MINCH were only observed at high concentrations of 10 μM, which are three orders of magnitudes higher than the current concentrations of plasticizers in human serum. Overall, the assessment of the effects of DINCH and MINCH on SGBS cells by metabolomics revealed no adipogenic potential at physiologically relevant concentrations. This finding aligns with previous in vivo studies and supports the potential of our method as a New Approach Method (NAM) for the assessment of adipogenic effects of environmental chemicals.
    Language English
    Publishing date 2024-04-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 205699-9
    ISSN 1096-0953 ; 0013-9351
    ISSN (online) 1096-0953
    ISSN 0013-9351
    DOI 10.1016/j.envres.2024.118847
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Emerging Plasticizer Alternative DINCH and Its Metabolite MINCH Induce Oxidative Stress and Enhance Inflammatory Responses in Human THP-1 Macrophages.

    Schaffert, Alexandra / Arnold, Josi / Karkossa, Isabel / Blüher, Matthias / von Bergen, Martin / Schubert, Kristin

    Cells

    2021  Volume 10, Issue 9

    Abstract: The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been ...

    Abstract The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been described to be a driving factor. The emerging alternative plasticizer 1,2-cyclohexanedioic acid diisononyl ester (DINCH) still lacks information regarding its potential effects on the immune system. Here, we investigated the effects of DINCH and its naturally occurring metabolite monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to 10 nM-10 μM DINCH or MINCH for 4 h, 16 h, and 24 h. To decipher the underlying mechanism of action, we applied an untargeted proteomic approach that revealed xenobiotic-induced activation of immune-related pathways such as the nuclear factor κB (NF-κB) signaling pathway. Key drivers were associated with oxidative stress, mitochondrial dysfunction, DNA damage repair, apoptosis, and autophagy. We verified increased reactive oxygen species (ROS) leading to cellular damage, NF-κB activation, and subsequent TNF and IL-1β release, even at low nM concentrations. Taken together, DINCH and MINCH induced cellular stress and pro-inflammatory effects in macrophages, which may lead to adverse health effects.
    MeSH term(s) Apoptosis/drug effects ; DNA Damage/drug effects ; DNA Repair/drug effects ; Dicarboxylic Acids/metabolism ; Esters/metabolism ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; NF-kappa B/metabolism ; Oxidative Stress/drug effects ; Phthalic Acids/metabolism ; Plasticizers/pharmacology ; Proteomics ; Signal Transduction/drug effects ; THP-1 Cells/drug effects ; THP-1 Cells/metabolism
    Chemical Substances Dicarboxylic Acids ; Esters ; NF-kappa B ; Phthalic Acids ; Plasticizers ; phthalic acid (6O7F7IX66E)
    Language English
    Publishing date 2021-09-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10092367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Does the presence of a specialist doctor reduce the burden of disease in people with epilepsy in low-resource settings? A comparison of two epilepsy clinics in rural Tanzania.

    Klein, Ana / Berger, Toni Christoph / Hapfelmeier, Alexander / Schaffert, Matthias / Matuja, William / Schmutzhard, Erich / Winkler, Andrea S

    Epilepsy & behavior : E&B

    2022  Volume 139, Page(s) 109030

    Abstract: Background: With an estimated lifetime prevalence of epilepsy of 7.6 per 1,000 people, epilepsy represents one of the most common neurological disorders worldwide, with the majority of people with epilepsy (PWE) living in low-income and middle-income ... ...

    Abstract Background: With an estimated lifetime prevalence of epilepsy of 7.6 per 1,000 people, epilepsy represents one of the most common neurological disorders worldwide, with the majority of people with epilepsy (PWE) living in low-income and middle-income countries (LMICs). Adequately treated, up to 70 % of PWE will become seizure-free, however, as many as 85% of PWE worldwide, mostly from LMICs, do not receive adequate treatment.
    Objective: To assess the impact of the presence of a neurologist on the management of PWE in Tanzania.
    Methods: Two epilepsy clinics in rural Tanzania, one continuously attended by a neurologist, and one mainly attended by nurses with training in epilepsy and supervised intermittently by specialist doctors (neurologists/psychiatrists) were comparatively analyzed by multivariable linear and logistic regression models with regard to the outcome parameters seizure frequency, the occurrence of side effects of antiepileptic medication and days lost after a seizure.
    Results: The presence of a neurologist significantly reduced the mean number of seizures patients experienced per month by 4.49 seizures (p < 0.01) while leading to an increase in the occurrence of reported side effects (OR: 2.15, p = 0.02).
    Conclusion: The presence of a neurologist may play a substantial role in reducing the burden of the disease of PWE in LMICs. Hence, specialist training should be encouraged, and relevant context-specific infrastructure established.
    MeSH term(s) Humans ; Tanzania/epidemiology ; Epilepsy/therapy ; Epilepsy/drug therapy ; Anticonvulsants/therapeutic use ; Seizures/drug therapy ; Cost of Illness
    Chemical Substances Anticonvulsants
    Language English
    Publishing date 2022-12-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2022.109030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARγ activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes.

    Schaffert, Alexandra / Karkossa, Isabel / Ueberham, Elke / Schlichting, Rita / Walter, Katharina / Arnold, Josi / Blüher, Matthias / Heiker, John T / Lehmann, Jörg / Wabitsch, Martin / Escher, Beate I / von Bergen, Martin / Schubert, Kristin

    Environment international

    2022  Volume 164, Page(s) 107279

    Abstract: The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe ... ...

    Abstract The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome.
    MeSH term(s) Adipocytes/metabolism ; Adipogenesis ; Diethylhexyl Phthalate/metabolism ; Diethylhexyl Phthalate/toxicity ; Homeostasis ; Humans ; Lipids ; Obesity/metabolism ; Oxidative Stress ; PPAR gamma/metabolism ; Phthalic Acids ; Plasticizers/metabolism ; Plasticizers/toxicity
    Chemical Substances Lipids ; PPAR gamma ; Phthalic Acids ; Plasticizers ; phthalic acid (6O7F7IX66E) ; Diethylhexyl Phthalate (C42K0PH13C)
    Language English
    Publishing date 2022-05-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARγ activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes

    Schaffert, Alexandra / Karkossa, Isabel / Ueberham, Elke / Schlichting, Rita / Walter, Katharina / Arnold, Josi / Blüher, Matthias / Heiker, John T. / Lehmann, Jörg / Wabitsch, Martin / Escher, Beate I. / von Bergen, Martin / Schubert, Kristin

    Environment international. 2022 June, v. 164

    2022  

    Abstract: The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe ... ...

    Abstract The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome.
    Keywords adipocytes ; adipogenesis ; adipose tissue ; agonists ; environment ; high fat diet ; homeostasis ; humans ; insulin resistance ; leptin ; lipids ; metabolic syndrome ; metabolites ; obesity ; oxidative stress ; pandemic ; peroxisome proliferator-activated receptor gamma ; phthalates ; plasticizers ; proteomics ; secretion
    Language English
    Dates of publication 2022-06
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107279
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins.

    Krieg, Laura / Schaffert, Alexandra / Kern, Matthias / Landgraf, Kathrin / Wabitsch, Martin / Beck-Sickinger, Annette G / Koerner, Antje / Blüher, Matthias / von Bergen, Martin / Schubert, Kristin

    Molecules (Basel, Switzerland)

    2020  Volume 25, Issue 4

    Abstract: Adipokines and apolipoproteins are key regulators and potential biomarkers in obesity and associated diseases and their quantitative assessment is crucial for functional analyses to understand disease mechanisms. Compared to routinely used ELISAs, ... ...

    Abstract Adipokines and apolipoproteins are key regulators and potential biomarkers in obesity and associated diseases and their quantitative assessment is crucial for functional analyses to understand disease mechanisms. Compared to routinely used ELISAs, multiple reaction monitoring (MRM)-based mass spectrometry allows multiplexing and detection of proteins for which antibodies are not available. Thus, we established an MRM method to quantify 9 adipokines and 10 apolipoproteins in human serum. We optimized sample preparation by depleting the two most abundant serum proteins for improved detectability of low abundant proteins. Intra-day and inter-day imprecision were below 16.5%, demonstrating a high accuracy. In 50 serum samples from participants with either normal weight or obesity, we quantified 8 adipokines and 10 apolipoproteins. Significantly different abundances were observed for five adipokines (adipsin, adiponectin, chemerin, leptin, vaspin) and four apolipoproteins (apo-B100/-C2/-C4/-D) between the body mass index (BMI) groups. Additionally, we applied our MRM assay to serum samples from normal weight children and human adipocyte cell culture supernatants to proof the feasibility for large cohort studies and distinct biological matrices. In summary, this multiplexed assay facilitated the investigation of relationships between adipokines or apolipoproteins and phenotypes or clinical parameters in large cohorts, which may contribute to disease prediction approaches in the future.
    MeSH term(s) Adipocytes/metabolism ; Adipokines/blood ; Adipokines/chemistry ; Adult ; Age Factors ; Apolipoproteins/blood ; Apolipoproteins/chemistry ; Biomarkers ; Child ; Chromatography, High Pressure Liquid ; Humans ; Mass Spectrometry/methods ; Sensitivity and Specificity ; Tandem Mass Spectrometry
    Chemical Substances Adipokines ; Apolipoproteins ; Biomarkers
    Language English
    Publishing date 2020-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules25040775
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The displaced supracondylar humerus fracture: indications for surgery and surgical options: a 2014 update.

    Ladenhauf, Hannah N / Schaffert, Matthias / Bauer, Jan

    Current opinion in pediatrics

    2014  Volume 26, Issue 1, Page(s) 64–69

    Abstract: Purpose of review: Supracondylar humerus fractures are the most common elbow fractures in children. Choice of treatment may be guided by the Gartland classification. Recent studies recommend conservative management for non or minimally displaced ... ...

    Abstract Purpose of review: Supracondylar humerus fractures are the most common elbow fractures in children. Choice of treatment may be guided by the Gartland classification. Recent studies recommend conservative management for non or minimally displaced fractures, whereas there seems to be a trend towards surgical intervention for all displaced fractures. The purpose of this review is to discuss the various treatment options for displaced supracondylar humerus fractures.
    Recent findings: Closed reduction and percutaneous pinning are the preferred treatment options for most displaced pediatric supracondylar fractures of the humerus. The ideal pin configuration has always been subject to great controversy. It is well known that placement of a medial pin carries the risk of iatrogenic ulnar nerve injury, whereas lateral pinning carries an increased risk of median neuropathy. Therefore, given the potential risk, it is recommended to avoid medial pinning to prevent damage to the ulnar nerve and stabilize the fracture with two or three lateral pins.
    Summary: Today, the preferred treatment of displaced supracondylar humerus fractures in children is immediate closed reduction and percutaneous fixation with two or three lateral pins. In case of instability of the medial column, a medial pin may be used, but possibility of iatrogenic ulnar nerve injury should be considered.
    MeSH term(s) Bone Nails ; Child ; Elbow Joint/diagnostic imaging ; Elbow Joint/injuries ; Elbow Joint/surgery ; Fracture Fixation/adverse effects ; Fracture Fixation/methods ; Humans ; Humeral Fractures/diagnostic imaging ; Humeral Fractures/surgery ; Peripheral Nerve Injuries/etiology ; Peripheral Nerve Injuries/prevention & control ; Radiography ; Ulnar Nerve/injuries
    Language English
    Publishing date 2014-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1049374-8
    ISSN 1531-698X ; 1040-8703
    ISSN (online) 1531-698X
    ISSN 1040-8703
    DOI 10.1097/MOP.0000000000000044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARγ activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes

    Alexandra Schaffert / Isabel Karkossa / Elke Ueberham / Rita Schlichting / Katharina Walter / Josi Arnold / Matthias Blüher / John T. Heiker / Jörg Lehmann / Martin Wabitsch / Beate I. Escher / Martin von Bergen / Kristin Schubert

    Environment International, Vol 164, Iss , Pp 107279- (2022)

    2022  

    Abstract: The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe ... ...

    Abstract The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome.
    Keywords Peroxisome proliferator-activated receptor γ (PPARγ) ; Plasticizers ; Endocrine disruption ; Oxidative stress ; SGBS ; Proteomics ; Environmental sciences ; GE1-350
    Subject code 500
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Austrian study shows that delays in accessing acute paediatric health care outweighed the risks of COVID-19.

    Schaffert, Matthias / Zimmermann, Franz / Bauer, Leopold / Kastner, Simon / Schwarz, Astrid / Strenger, Volker / Metzger, Roman / Thun-Hohenstein, Leonhard / Sperl, Wolfgang / Weghuber, Daniel / Wortmann, Saskia B

    Acta paediatrica (Oslo, Norway : 1992)

    2020  Volume 109, Issue 11, Page(s) 2309–2310

    MeSH term(s) Adolescent ; Austria ; COVID-19 ; Child ; Child, Preschool ; Emergency Service, Hospital/statistics & numerical data ; Humans ; Infant ; Pandemics ; Pediatrics/statistics & numerical data ; Retrospective Studies ; Time-to-Treatment
    Keywords covid19
    Language English
    Publishing date 2020-08-19
    Publishing country Norway
    Document type Journal Article
    ZDB-ID 203487-6
    ISSN 1651-2227 ; 0365-1436 ; 0803-5253
    ISSN (online) 1651-2227
    ISSN 0365-1436 ; 0803-5253
    DOI 10.1111/apa.15507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins

    Laura Krieg / Alexandra Schaffert / Matthias Kern / Kathrin Landgraf / Martin Wabitsch / Annette G. Beck-Sickinger / Antje Körner / Matthias Blüher / Martin von Bergen / Kristin Schubert

    Molecules, Vol 25, Iss 4, p

    2020  Volume 775

    Abstract: Adipokines and apolipoproteins are key regulators and potential biomarkers in obesity and associated diseases and their quantitative assessment is crucial for functional analyses to understand disease mechanisms. Compared to routinely used ELISAs, ... ...

    Abstract Adipokines and apolipoproteins are key regulators and potential biomarkers in obesity and associated diseases and their quantitative assessment is crucial for functional analyses to understand disease mechanisms. Compared to routinely used ELISAs, multiple reaction monitoring (MRM)-based mass spectrometry allows multiplexing and detection of proteins for which antibodies are not available. Thus, we established an MRM method to quantify 9 adipokines and 10 apolipoproteins in human serum. We optimized sample preparation by depleting the two most abundant serum proteins for improved detectability of low abundant proteins. Intra-day and inter-day imprecision were below 16.5%, demonstrating a high accuracy. In 50 serum samples from participants with either normal weight or obesity, we quantified 8 adipokines and 10 apolipoproteins. Significantly different abundances were observed for five adipokines (adipsin, adiponectin, chemerin, leptin, vaspin) and four apolipoproteins (apo-B100/-C2/-C4/-D) between the body mass index (BMI) groups. Additionally, we applied our MRM assay to serum samples from normal weight children and human adipocyte cell culture supernatants to proof the feasibility for large cohort studies and distinct biological matrices. In summary, this multiplexed assay facilitated the investigation of relationships between adipokines or apolipoproteins and phenotypes or clinical parameters in large cohorts, which may contribute to disease prediction approaches in the future.
    Keywords adipokines ; apolipoproteins ; multiple reaction monitoring ; targeted lc-ms ; obesity ; human serum ; sgbs cells ; cell culture supernatant ; Organic chemistry ; QD241-441
    Subject code 616
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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