Trigger for fatty liver in obesity

Trigger for fatty liver in obesity
 

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.

Despite the increasing frequency of obesity-related liver steatosis, there is currently insufficient knowledge about the origin of this disease. The researchers 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.

"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 the senior author. "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," senior author explains.

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.

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," senior author explains.

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

https://www.nature.com/articles/s41467-017-00566-9

Edited

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