Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Trigger for Fatty Liver in Obesity

07.09.2017

Morbid obesity affects the liver: Almost one-third of all adults suffer from chronic fatty liver disease, which can lead to infections and even trigger cancer. Researchers at the University Children's Hospital Zurich and the University of Zurich have now found a signaling pathway in cells that play an important role in the development of fatty liver disease.

In Switzerland, about every tenth adult suffers from morbid obesity. Such corpulence can not only lead to diabetes or cardiovascular disease, but also to fat accumulation in the liver. Worldwide, about 25 to 30 percent of all adults and increasingly children are affected by such steatosis – becoming the most frequent liver disease in recent years. Some patients suffer from inflammation that could lead to a scarred shrinkage of the liver (cirrhosis) or even cancer.


A healthy liver (left) can develo a steatosis (right).

Image UZH

Receptor for programmed cell death activated

Despite the increasing frequency of obesity-related liver steatosis, there is currently insufficient knowledge about the origin of this disease. At the University Children's Hospital Zurich, researchers from the University of Zurich have identified a signaling pathway in liver cells that may contribute to the development of steatosis.

In the process, the plasma membrane receptor Fas (CD95) is key; this cell receptor occurs in almost all human cells and is involved in programmed cell death (apoptosis). This self-destruction program is activated when cells are no longer functional or are even developing malignantly. Activation of the Fas receptor then induces apoptosis in these cells. A low-threshold activation of Fas, however, can trigger cell reproduction or an inflammatory response without cell death occurring.

Lack of Fas receptor protects against a fatty liver

“In our study, we were able to demonstrate in mouse models that Fas is activated within the scope of obesity and can therefore lead to the development of liver steatosis,” says Prof. Dr. med. Daniel Konrad, professor for endocrinology and diabetology from the University of Zurich and physician at the University Children's Hospital Zurich.

“Mice missing Fas in their liver cells were protected against the development of obesity-induced fatty liver for the most part.” The animals are also considerably less insulin resistant. “Conversely, our study shows that an increased Fas content in the liver can lead to liver steatosis and insulin resistance, even in case of a normal body weight,” Konrad explains.

Permeable mitochondria inhibit lipid oxidation

The team of researchers found indications that an activation of Fas affects the mitochondria: Their capacity to oxidize fatty acids is limited and therefore leads to the accumulation of lipids in liver cells. In the process, the protein-coded gene “BID” plays an important role. This gene is also involved in programmed cell death, leading to an increased permeability of the mitochondrial membrane. The researchers were able to demonstrate that mice with increased Fas content but simultaneously low BID content in the liver were protected against the development of fatty liver.

New therapy approach possible

The study therefore shows how both factors, Fas and BID, interact in case of obesity contributing to fatty liver disease. “The described signaling pathway of Fas and BID could serve as a novel target for a better treatment of fatty liver disease associated with obesity,” Daniel Konrad explains.

Literature:
Flurin Item, Stephan Wueest, Vera Lemos, Sokrates Stein, Fabrizio C. Lucchini, Rémy Denzler, Muri-el C. Fisser, Tenagne D. Challa, Eija Pirinen, Youngsoo Kim, Silvio Hemmi, Erich Gulbins, Atan Gross, Lorraine A. O’Reilly, Markus Stoffel, Johan Auwerx, Daniel Konrad. Fas Cell Surface Death Receptor controls hepatic lipid metabolism by regulating mitochondrial function. Nature Communica-tions. 7. September, 2017.DOI: 10.1038/s41467-017-00566-9

Contact:
Prof. Dr. med. Daniel Konrad
Endocrinology / Diabetology
University Children's Hospital Zurich
Phone: +41 44 266 73 85
E-mail: daniel.konrad@kispi.uzh.ch

Weitere Informationen:

http://www.media.uzh.ch/en/Press-Releases/2017/Fatty-Liver-in-Obesity.html

Melanie Nyfeler | Universität Zürich

More articles from Health and Medicine:

nachricht Dengue takes low and slow approach to replication
12.01.2018 | Duke University

nachricht Fast food makes the immune system more aggressive in the long term
12.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

Im Focus: Autoimmune Reaction Successfully Halted in Early Stage Islet Autoimmunity

Scientists at Helmholtz Zentrum München have discovered a mechanism that amplifies the autoimmune reaction in an early stage of pancreatic islet autoimmunity prior to the progression to clinical type 1 diabetes. If the researchers blocked the corresponding molecules, the immune system was significantly less active. The study was conducted under the auspices of the German Center for Diabetes Research (DZD) and was published in the journal ‘Science Translational Medicine’.

Type 1 diabetes is the most common metabolic disease in childhood and adolescence. In this disease, the body's own immune system attacks and destroys the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fachtagung analytica conference 2018

15.01.2018 | Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

 
Latest News

Black hole spin cranks-up radio volume

15.01.2018 | Physics and Astronomy

A matter of mobility: multidisciplinary paper suggests new strategy for drug discovery

15.01.2018 | Life Sciences

New method to map miniature brain circuits

15.01.2018 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>