David Meierhofer

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About David Meierhofer:

No description specified

SEEK ID: https://seek.lisym.org/people/11

Location: Germany

ORCID: Not specified

Joined: 28th Apr 2017

Expertise: Mass spectrometry

Tools: Proteomics, Metabolomics, Mitochondrial disorders

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Other Projects: LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi) (Max Planck Institute for Molecular Genetics (MPI-MG)) ; LiSyM network (Max Planck Institute for Molecular Genetics (MPI-MG))

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LiSyM: Liver Systems Medicine

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

Web page: https://www.lisym.org/

LiSyM network

This comprises the whole LiSyM network

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org

Start date: 1st Jan 2016

Organisms: Rattus norvegicus, Rattus rattus, Mus musculus, Homo sapiens

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Disorders of the liver show up through changes in blood tests. These blood tests indicate markers for events taking place in the liver. Usually studies of liver tissue cannot be performed: as liver samples would need to be obtained through a liver biopsy, and this procedure is not without risk, therefore these samples are usually unavailable. Complex metabolism models based on existing and new scientific data can simulate changes in the liver caused by disease. They often reveal unknown relationships ...

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research/the-liver-is-very-patient

Start date: 1st Jan 2016

Organisms: Homo sapiens

Max Planck Institute for Molecular Genetics (MPI-MG)

Country: Germany

City: 14195 Berlin

Web page: https://www.molgen.mpg.de/

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Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife …

Authors: S. Schreyer, N. Berndt, J. Eckstein, M. Mulleder, S. Hemmati-Sadeghi, C. Klein, B. Abuelnor, A. Panzel, D. Meierhofer, J. Spranger, B. Steiner, S. Brachs

Date Published: 16th Apr 2021

Publication Type: Journal

PubMed ID: 33864446

Citation: Aging (Albany NY). 2021 Apr 16;13(8):10891-10919. doi: 10.18632/aging.202978. Epub 2021 Apr 16.

Created: 14th May 2021 at 14:11

Regulation of the cytochrome P450 epoxyeicosanoid pathway is associated with distinct histologic features in pediatric non-alcoholic fatty liver disease.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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Non-alcoholic fatty liver disease (NAFLD) is a significant health burden in obese children for which there is currently no specific therapy. Preclinical studies indicate that epoxyeicosanoids, a class …

Authors: L. Kalveram, W. H. Schunck, M. Rothe, B. Rudolph, C. Loddenkemper, H. G. Holzhutter, S. Henning, P. Bufler, M. Schulz, D. Meierhofer, I. W. Zhang, K. H. Weylandt, S. Wiegand, C. A. Hudert

Date Published: 4th Jan 2021

Publication Type: Journal

PubMed ID: 33388475

Citation: Prostaglandins Leukot Essent Fatty Acids. 2021 Jan;164:102229. doi: 10.1016/j.plefa.2020.102229. Epub 2020 Dec 17.

Created: 4th Feb 2021 at 07:30

Metabolic heterogeneity of human hepatocellular carcinoma: implications for personalized pharmacological treatment.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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Metabolic reprogramming is a characteristic feature of cancer cells, but there is no unique metabolic program for all tumors. Genetic and gene expression studies have revealed heterogeneous inter- and …

Authors: N. Berndt, J. Eckstein, N. Heucke, T. Wuensch, R. Gajowski, M. Stockmann, D. Meierhofer, H. G. Holzhutter

Date Published: 8th Oct 2020

Publication Type: Journal

PubMed ID: 33030799

Citation: FEBS J. 2020 Oct 8. doi: 10.1111/febs.15587.

Created: 11th Dec 2020 at 11:34

Functional consequences of metabolic zonation in murine livers: New insights for an old story.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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BACKGROUND & AIMS: Zone-dependent differences in the expression of metabolic enzymes along the porto-central axis of the acinus are a long-known feature of liver metabolism. A prominent example is …

Authors: N. Berndt, E. Kolbe, R. Gajowski, J. Eckstein, F. Ott, D. Meierhofer, H. G. Holzhutter, M. Matz-Soja

Date Published: 14th Apr 2020

Publication Type: Not specified

PubMed ID: 32286709

Citation: Hepatology. 2020 Apr 14. doi: 10.1002/hep.31274.

Created: 15th Jun 2020 at 13:29

A novel variant of the (13)C-methacetin liver function breath test that eliminates the confounding effect of individual differences in systemic CO2 kinetics.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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The principle of dynamic liver function breath tests is founded on the administration of a (13)C-labeled drug and subsequent monitoring of (13)CO2 in the breath, quantified as time series delta over … natural baseline (13)CO2 (DOB) liberated from the drug during hepatic CYP-dependent detoxification. One confounding factor limiting the diagnostic value of such tests is that only a fraction of the liberated (13)CO2 is immediately exhaled, while another fraction is taken up by body compartments from which it returns with delay to the plasma. The aims of this study were to establish a novel variant of the methacetin-based breath test LiMAx that allows to estimate and to eliminate the confounding effect of systemic (13)CO2 distribution on the DOB curve and thus enables a more reliable assessment of the hepatic detoxification capacity compared with the conventional LiMAx test. We designed a new test variant (named "2DOB") consisting of two consecutive phases. Phase 1 is initiated by the intravenous administration of (13)C-bicarbonate. Phase 2 starts about 30 min later with the intravenous administration of the (13)C-labelled test drug. Using compartment modelling, the resulting 2-phasic DOB curve yields the rate constants for the irreversible elimination and the reversible exchange of plasma (13)CO2 with body compartments (phase 1) and for the detoxification and exchange of the drug with body compartments (phase 2). We carried out the 2DOB test with the test drug (13)C-methacetin in 16 subjects with chronic liver pathologies and 22 normal subjects, who also underwent the conventional LiMAx test. Individual differences in the systemic CO2 kinetics can lead to deviations up to a factor of 2 in the maximum of DOB curves (coefficient of variation CV approximately 0.2) which, in particular, may hamper the discrimination between subjects with normal or mildly impaired detoxification capacities. The novel test revealed that a significant portion of the drug is not immediately metabolized, but transiently taken up into a storage compartment. Intriguingly, not only the hepatic detoxification rate but also the storage capacity of the drug, turned out to be indicative for a normal liver function. We thus used both parameters to define a scoring function which yielded an excellent disease classification (AUC = 0.95) and a high correlation with the MELD score (RSpearman = 0.92). The novel test variant 2DOB promises a significant improvement in the assessment of impaired hepatic detoxification capacity. The suitability of the test for the reliable characterization of the natural history of chronic liver diseases (fatty liver-fibrosis-cirrhosis) has to be assessed in further studies.

Authors: H. G. Holzhutter, T. Wuensch, R. Gajowski, N. Berndt, S. Bulik, D. Meierhofer, M. Stockmann

Date Published: 6th Feb 2020

Publication Type: Not specified

PubMed ID: 32020249

Citation: Arch Toxicol. 2020 Feb;94(2):401-415. doi: 10.1007/s00204-020-02654-0. Epub 2020 Feb 4.

Created: 15th Jun 2020 at 13:32

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