A European Consortium led by researcher James Adjaye, medical faculty of Heinrich Heine University-Duesseldorf and former Max-Planck researcher, identify a means of predicting the severity of Non Alcoholic Fatty Liver Disease (NAFLD) in a small cohort of patients. With an estimated prevalence of about 40 % in Europe and 50 % in the general world population, NAFLD, also referred to as steatosis, is a major public health issue highly related to our sedentary life style and high-fat diets. The prevalence is expected to increase rapidly leading to an epidemic status. The article was recently published in Nature Press - Scientific Data 2:150068 doi: 10.1038/sdata.2015.68 (2015).
It has been estimated in Europe that approximately 26 % or higher health costs account for NAFLD patients.NAFLD is a typical metabolic disease associated with obesity, insulin resistance and type 2 diabetes.
Abnormal fat deposits develop in patients’ livers. In general steatosis is without complications however associated with an increased risk of heart attacks and strokes. Furthermore, steatosis can progress to steatohepatitis and in some cases to cirrhosis and liver cancer.
There are also genetic mutations associations with the disease, for example within genes such as PNPLA3 and TM6SF2. Taken together, NAFLD is caused by a complex interplay of genetic and environmental factors.
Therefore to gain insights into disease causing mechanisms James Adjaye co-ordinated the livSYSiPS consortium, which was co-funded by the German Federal Ministry of Education and Research (BMBF), a partner of the ERASysBio+ initiative supported under the EU ERA-NET Plus scheme in FP7. The ERASysBio+ initiative aimed at advancing the progress of systems biology research in Europe. The multi-national consortium with research groups from Germany, UK, Italy and Austria employed a systems biology approach to investigate the etiology of NAFLD.
The underlying study discovered higher amounts of the gene PLIN2 in NAFLD patients. PLIN2 is involved in the aggregation of the fat deposits in the liver. Mice without this protein do not become fat even when overfed with a high-fat diet.
Additional findings in blood serum of these patients include differences in the levels of the appetite-controlling hormone LEPTIN, ADIPONECTIN and amino acids which control the break-down of fat. Furthermore, changes in the complex signaling cascades of insulin were detected which is the main regulation mechanism of glucose and fat balance.
These distinctions are an encouraging basis for further research encompassing a much larger cohort of patients with the potential to find novel means for diagnosing NAFLD and eventually new therapies.
Essential for this goal is good quality systems biology-based datasets and models and the sharing of data between researchers to catalyze scientific progress. Wasco Wruck, Bioinformatician and first author of the study, says:
”From our multi-disciplinary measurements we got amazing datasets from which we could draw interesting findings and hypothesis about NAFLD. We need further patient cohorts and experiments to confirm our initial results and to improve our systems biology models. In order to allow other researchers to work on this valuable data we deposited it in public repositories.”
To gain further insights to the cause of the disease at the level of individuals, which is the new era of personalized medicine, James Adjaye’s team are now generating induced pluripotent stem cells (iPSCs) from skin cells from these patients and matching healthy controls. These patient-specific iPSCs are then turned into hepatocytes which are cells within the liver with the view of mimicking the patient’s liver metabolism in a dish.
To induce steatosis we add excess fat (e.g. oleic acid) to these cells and then analyse changes in gene, protein and metabolite levels as we originally did with the original liver biopsy and blood serum samples. Our goal now is to see if our “disease in a dish” model mirrors that seen in the patient, define new biomarkers of NAFLD and identify pathways as putative drug targets that can be used to complement current therapies for NAFLD says James Adjaye who is the senior author of the current publication.
Wasco Wruck, Karl Kashofer, Samrina Rehman, Andriani Daskalaki, Daniela Berg, Ewa Gralka, Justyna Jozefczuk, Katharina Drews, Vikash Pandey, Christian Regenbrecht, Christoph Wierling, Paola Turano, Ulrike Korf, Kurt Zatloukal, Hans Lehrach, Hans Westerhoff, and James Adjaye
Multi-omic profiles of human non-alcoholic fatty liver disease tissue highlight heterogenic phenotypes
Nature Press - Scientific Data 2:150068 doi: 10.1038/sdata.2015.68 (2015)
Susanne Dopheide | idw - Informationsdienst Wissenschaft
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Earth Sciences
29.05.2017 | Life Sciences
29.05.2017 | Physics and Astronomy