Non-alcoholic fatty liver: Another genetic cause discovered
Although a lot of people in the term “fatty liver” think fast of alcohol, but fatty liver disease there are other causes. Researchers have now discovered a further genetic trigger for non-alcoholic fatty liver (NAFL).
The German liver Foundation indicates that around a third of the adults has a fatty deposits enlarged liver and the number is steadily increasing. A distinction is made between non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL). Among the causes that lead mostly in combinations of a fatty liver, in addition to poor diet, lack of exercise and Obesity, high alcohol consumption or a history of diabetes. Researchers have now discovered another cause.
About 18 million people in Germany are affected
According to a recent communication of the German center for diabetes research (DZD) to suffer about 18 million people in Germany a non-alcoholic fatty liver. The causes of this disease are varied and include both environmental and genetic factors.
Scientists of the DZD have now discovered new genes play in the development of a fatty liver a role.
The genes IRGM, Ifgga2 and Ifgga4 concerns in humans or mice for the production of regulatory proteins of the family of immune-associated GTPases, which is a fat accumulation counter in the liver. A genetic change leads to less of these proteins to be formed.
The results were published recently in the journal “Journal of Hepatology”.
Unhealthy life style and genetic predisposition
According to the DZD non-alcoholic fatty liver (nonalcoholic fatty liver disease, NAFLD) in Europe and the USA, the disease is the most common cause of chronic liver. In Europe, approximately 20-30 percent of the population suffer, therefore, it.
NAFLD is often associated with other diseases such as obesity (obesity), type 2 Diabetes, high blood pressure (arterial hypertension) and lipid metabolic disorder (dyslipidemia).
In addition to an unhealthy lifestyle with a high fat – and sugar-rich diet and lack of exercise is also a genetic predisposition to the development of this liver disease is responsible.
The NAFLD is a complex disease for which there is not only a Krankheitsgen. Rather, the interactions of different genes as well as epigenetic factors play a role. Researchers have now discovered a new gene family, which plays an important role in the prevention of fatty liver formation.
These genes provide in humans and also in mice for the production of regulatory proteins of the family of immune-associated GTPases, which is a fat accumulation counter in the liver.
A genetic change is, however, formed less proteins. Studies show that the liver of patients with NAFLD and mice with fatty liver significantly lower amounts of these proteins.
The study, led a research team of the German Institute for nutritional research Potsdam-Rehbrücke (DIfE), the German Diabetes center (DDZ) and the Helmholtz Zentrum München by all the partners of the DZD.
New genes identified
The information suggests that by using molecular markers and statistical methods (QTL analysis Quantitative Trait Locus) in mouse strains have identified genes for complex human diseases.
The research team discovered an area on the mouse chromosome 18 that was associated with changes in the amounts of fat in the liver. If the genes are read Ifgga2 and Ifgga4, incurred by proteins of the family of immune-associated GTPases in the mouse the Protein IFGGA2 and IFGGA4 and in humans the Protein IRGM.
According to the experts, these proteins increase a certain Form of fat reduction and to counteract the emergence of a fatty liver.
In humans but also in mice with a fatty liver, the genes are expressed, but significantly less. This is caused by a small genetic change in mice.
“Due to the loss of only one Base in a gene sequence, the amplified Reading of a particular gene are produced the two related proteins IFGGA2 and IFGGA4 barely in liver cells of mice, which are prone to a fatty liver,” explains Professor Annette Schürmann, head of the Department of Experimental diabetology at the DIfE and spokeswoman for the DZD.
Also, patients with NAFLD have significantly lower amounts of the corresponding Protein (IRGM). As a result, the fat content can rise in the liver to the three – to four-fold.
Researchers want to be able to help out such as diets or medication
De communication, functional studies have shown that an Overproduction of the immune-associated GTPases reduced in liver cells or in the liver of the mouse the fat content significantly.
“The reason is the induction of a specific Form of Autophagy, which is specific for the breakdown of fats and therefore Lipophagie is called,” explains Dr. Wenke Jonas, who has co-chaired with Prof. Schürmann the study.
Autophagy is degraded according to the experts, a kind of cellular waste disposal and Recycling process, the cell’s own components.
The researchers observed that after absorption of fatty acids in liver cells, the immune-associated GTPases Hiking to the fat-drops, there of an enzyme of fat reduction (adipocyte triglyceride Lipase) bind and ensure that a key Protein in Autophagy (LC3B) and the fat drops binds.
Through the Autophagy of lipid, the amount of fat is reduced and so the formation of a fat prevents the liver droplets accordingly.
The immune-associated GTPases affect the amount of fat in the liver, were able to show the scientists also through the two following tests: Inhibited the synthesis of proteins, saved mice more fat in the liver cells. The production of proteins in liver cells was increased, however, a stored significantly less fat.
“Through our Work in other important genes were identified, which lead to a fatty liver disease. In addition, the results of the study deepen our understanding of which cellular processes are stimulated to counteract the effects of fatty liver,“ says Schürmann.
“Our next goal is to now clarify what measures – such as diet or certain medications – the amount of the immune-associated GTPases can be increase so as to reduce the storage of fat in the liver.” (ad)