Health: Why overweight leads to fatty liver

Triggers of obesity were identified
Obesity has a variety of adverse health effects, including fatty liver, which at worst can lead to cancer. Scientists from the Children's Hospital Zurich and the University of Zurich have now shown the signaling pathways in the cells that play an important role in the formation of fatty liver. They also showed new treatment approaches that can prevent fatty liver formation.

Severe overweight or obesity "can not only lead to diabetes or cardiovascular diseases, but also to fatty liver," reports the University of Zurich. Around 25 to 30 percent of all adults and increasingly also children worldwide are affected by such so-called steatoses (fatty liver). Some of those affected develop inflammation of the liver, which can lead to cirrhosis and ultimately liver cancer. The Zurich researchers have now deciphered the signaling pathways that lead to the formation of fatty liver disease when overweight.

Cell receptor Fas vital
Although it was already known that obesity is associated with an increased risk of liver steatosis, the underlying molecular biological mechanism remains largely unclear. In their current study, however, the scientists were able to identify signaling pathways in the cells, which obviously play an important role in this. The cell receptor Fas (CD95), which occurs in almost all human cells and is partly responsible for programmed cell death (apoptosis), is of central importance, reports the University of Zurich. This self-destruction program is activated when cells stop developing functionally or even malignantly.

Although activation of the Fas cell receptor normally kills the defective cells, low-threshold activation of Fas can also trigger cell proliferation or an inflammatory response without causing cell death, the researchers explain. "In our study, we were able to use the mouse model to show for the first time that obesity appears to be activated as part of an obesity and can thus contribute to the development of liver steatosis," reports Prof. Daniel Konrad, professor of endocrinology and diabetology at the University of Zurich and doctor at the Children's Hospital Zurich . Mice without Fas in the liver cells were largely protected from the development of such fatty liver.

Fatty liver and insulin resistance
In addition, the mice without Fas developed significantly less insulin resistance, the researchers report. And conversely, an increased Fas content in the liver, even with normal body weight, led to liver steatosis and corresponding insulin resistance, said Prof. Konrad. When searching for the causes of the action of the cell receptor, the scientists found that an activation of Fas affects the mitochondria and limits their capacity to burn fatty acids. This promotes fat accumulation in the liver cells. The protein-coding gene “BID” also plays an important role here. This also comes into play as part of the programmed cell death in the body and causes an increased permeability of the mitochondrial membrane.

New approaches to the treatment of obesity in the liver
In their investigations, the researchers were able to prove that not only mice without Fas, but also mice with increased Fas but at the same time low BID content in the liver are protected against the development of obesity-induced fatty liver. The study thus shows how the two factors Fas and BID interact in obesity and lead to fatty liver, reports the University of Zurich. The now identified "signaling pathways from the Fas and BID can serve as a new target for the development of medicines in order to better treat obesity in the liver", said Prof. (fp)

Author and source information

Video: Fatty Liver and Fasting Study 2020. Buchinger Wilhelmi (January 2022).