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Witigo Von Schönfels

About Witigo Von Schönfels:
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SEEK ID: https://seek.lisym.org/people/57

Location: Germany

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

Early Metabolic Injury (LiSyM-EMI - Pillar I)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. LiSyM-EMI looks into the transition from steatosis to non-alcoholic steatohepatitis (NASH) as the disease-defining moment in NAFLD. A systems analysis of these early disease events will be performed to elucidate the molecular mechanisms that trigger disease establishment.

Public web page: Not specified

Mouse expression dataset (Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.)
Early Metabolic Injury (LiSyM-EMI - Pillar I)

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify
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Creators: Mario Brosch, Jochen Hampe, Clemens Schafmayer, Witigo Von Schönfels

Contributor: Mario Brosch

Human expression dataset (Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.)
Early Metabolic Injury (LiSyM-EMI - Pillar I)

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify
...

Creators: Mario Brosch, Jochen Hampe, Clemens Schafmayer, Witigo Von Schönfels

Contributor: Mario Brosch

Electrosurgical liver resection has a superior regeneration outcome as compared to en-bloc ligation in a novel model of partial hepatectomy in mice
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

Background: The extent of resection and the frequency of liver surgery have increased over the past decades, enabled by improved haemostasis provided by electrosurgical liver dissection. Because extensive … liver surgery is still associated with lethal complications, further optimisation of the technique and a better molecular understanding of hepatic wound healing and regeneration are needed. Systematic studies and a mouse model reflecting the clinical reality of liver surgery are lacking. Methods: We performed liver resection in mice with a monopolar electrocautery device in comparison to the classical en-bloc ligation method. Regeneration was assessed using liver weight and BrDU immunohistochemistry after sacrifice and non-invasively using micro computed tomography (µCT). Results: Mortality in the electrosurgical model was similar to the ligation method given an identical extent of resection. Regeneration of liver proceeded significantly faster in the electrosurgical group: Liver weight was 25.6% higher at sacrifice after 168h (p=0.0003). Concordantly, both µCT analysis (22.6% higher liver volume at 168h, p=0.008) and BrDU staining (71.4% higher proliferation at 72h, p=0.0005) indicated superior regeneration of liver after electrosurgical partial hepatectomy. Conclusions: The mode of liver resection has a profound impact on regeneration and should be studied molecularly using the presented novel model of electrosurgical liver resection.

Authors: W. von Schonfels, Clemens Schafmayer, Jochen Hampe

Date Published: No date defined

Journal: prepublication

Histologic improvement of NAFLD in patients with obesity after bariatric surgery based on standardized NAS (NAFLD activity score).
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Nonalcoholic steatohepatitis is the fastest growing cause for liver failure. … Bariatric surgery represents a treatment option for NAFLD with an established effect on liver histology. OBJECTIVES: We aimed to assess the impact of bariatric surgery on standardized liver histology using the NAFLD activity score. SETTING: Retrospective comparison of metabolic data before and after bariatric surgery and comparison of sleeve gastrectomy and Roux-en-Y gastric bypass. The study was performed in an academic center, the university hospital Schleswig-Holstein in Kiel, Germany. METHODS: Between 2009 and 2012, bariatric surgery was performed in 257 patients according to the national guidelines, and a liver biopsy was obtained in 150 of these patients during surgery. A follow-up biopsy was available in 53 of these patients at a median of 192 days. Liver histology was analyzed using the NAFLD activity score. In this subgroup of 53 patients an analysis of the metabolic improvement after bariatric surgery and a comparative analysis between the 2 different operative procedures was performed. RESULTS: The study cohort showed improvement of preoperative pathologic liver histology findings after operative procedures took place. Both surgery methods improved the NAFLD activity score significantly, all improvement -2.0 (confidence interval -2.5 to -1.0; P < .001); Roux-en-Y gastric bypass, improvement -1.0 (confidence interval -2.0 to -.0; P=.038); sleeve gastrectomy, improvement -2.5 (confidence interval -3.5 to -1.5; P < .001). No differences were found with regard to histologic recovery between gastric bypass and sleeve gastrectomy (P = .22). CONCLUSIONS: Bariatric surgery significantly improves NAFLD.

Authors: Witigo Von Schönfels, J. H. Beckmann, M. Ahrens, A. Hendricks, C. Rocken, S. Szymczak, Jochen Hampe, Clemens Schafmayer

Date Published: 28th Aug 2018

Journal: Surg Obes Relat Dis

Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes … across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.

Authors: Mario Brosch, Kathrin Kattler, Alexander Herrmann, Witigo Von Schönfels, Karl Nordström, Daniel Seehofer, Georg Damm, Ann-Kristin Becker, Sebastian Zeissig, Sophie Nehring, Fabian Reichel, Vincent Moser, Raghavan Veera Thangapandi, Felix Stickel, Gustavo Baretton, Christoph Röcken, Michael Muders, Madlen Matz-Soja, Michael Krawczak, Gilles Gasparoni, Hella Hartmann, Andreas Dahl, Clemens Schafmayer, Jörn Walter, Jochen Hampe

Date Published: 1st Dec 2018

Journal: Nat Commun

Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control
The Hedgehog Signalling Pathway (LiSyM-JGMMS)

Abstract

Not specified

Authors: Mario Brosch, Kathrin Kattler, Alexander Herrmann, Witigo Von Schönfels, Karl Nordström, Daniel Seehofer, Georg Damm, Thomas Becker, Sebastian Zeissig, Sophie Nehring, Fabian Reichel, Vincent Moser, Raghavan Veera Thangapandi, Felix Stickel, Gustavo Baretton, Christoph Röcken, Michael Muders, Madlen Matz-Soja, Michael Krawczak, Gilles Gasparoni, Hella Hartmann, Andreas Dahl, Clemens Schafmayer, Jörn Walter, Jochen Hampe

Date Published: 1st Dec 2018

Journal: Nat Commun

Longitudinal micro-computed tomography monitoring of progressive liver regeneration in a mouse model of partial hepatectomy.
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

The partial hepatectomy (PH) model is widely used to study liver regeneration. Currently, the extent of regeneration is analyzed by measuring the weight of the liver post-mortem or by magnetic resonance … imaging. In this study we aimed to determine whether liver volume gain can be accurately measured using micro-computed tomography (microCT). Approximately 42% of the liver was removed by ligation in C57BL/6 N mice. Mice were divided into two study groups. In group 1 conventional characterization of liver hyperplasia was performed by weighing the liver post-mortem. In group 2, liver volume gain was determined by microCT volume estimation. MicroCT results showed equivalent regeneration rates compared with the conventional method without the need to mathematically determine initial liver weights before PH. This parameter is strongly influenced by the age, strain and sex of the mice. In addition non-invasive microCT determination of volume gain over multiple time-points using the same animal reduces the number of animals needing to be used (in line with the 3R principle of replacement, reduction and refinement).

Authors: O. M. Will, T. Damm, G. M. Campbell, Witigo Von Schönfels, Y. Acil, M. Will, A. Chalaris-Rissmann, M. Ayna, C. Drucker, C. C. Gluer

Date Published: No date defined

Journal: Lab Anim

Poster midterm evaluation Pillar I, WP6
Early Metabolic Injury (LiSyM-EMI - Pillar I)
No description specified

Creator: Witigo Von Schönfels

Contributor: Witigo Von Schönfels

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