Health Why overweight leads to fatty liver

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

Severe overweight or obesity "can not only lead to diabetes or cardiovascular diseases, but also to an obesity of the liver," reports the University of Zurich. About 25 to 30 percent of all adults worldwide and increasingly children are affected by steatosis (fatty liver). Some sufferers experience inflammation of the liver, which can cause cirrhosis of the liver and, ultimately, liver cancer. The Zurich researchers have now decoded the signaling pathways that lead to the development of fatty liver in severe obesity.

Swiss scientists have identified the signaling pathways that adiposity causes to obstruct the liver. This also opens new treatment approaches against fatty liver in severe obesity. (Image: MartesiaBezuidenhout / fotolia.com)

Cell receptor Fas is crucial
Although adiposity (obesity) has been reported to increase the risk of liver steatosis, the underlying mechanism of molecular biology remains largely unclear. In their current study, however, the scientists have identified signaling pathways in the cells, which obviously play an important role. Of central importance is the cell receptor Fas (CD95), which is found in almost all human cells and is responsible for programmed cell death (apoptosis), reports the University of Zurich. This self-destruct program is activated when cells are no longer functional or even malignant.

Although activation of the cell receptor Fas normally destroys the defective cells, a low-threshold activation of Fas can also trigger cell proliferation or an inflammatory reaction without resulting in cell death, the researchers explain. "In our study, we were able to demonstrate for the first time on mouse models that obesity apparently activates Fas, thus contributing to the development of liver steatosis," reports Prof. Daniel Konrad, Professor of Endocrinology and Diabetology at the University of Zurich and physician at the Children's Hospital Zurich , Non-Fas mice in liver cells were largely protected from developing such fatty liver.

Liver adiposity and insulin resistance
Furthermore, the mice without Fas also developed a significantly lower insulin resistance, the researchers report. Conversely, an increased content of Fas in the liver, even at normal body weight, has led to liver steatosis and to a corresponding insulin resistance, said Prof. Konrad. In their search for the causes of the cell receptor's action, the scientists found that activation of Fas affects the mitochondria and limits their capacity to burn fatty acids. This promotes fat accumulation in the liver cells. The protein-encoding gene "BID" also plays an important role here. It also contributes to programmed cell death in the body and causes increased permeability of the mitochondrial membrane.

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