Cachexia or wasting is a condition affecting up to 70 percent of cancer patients, depending on the type of cancer. It is characterized by a dramatic loss of body weight that is independent of food intake. Cachexia is seen particularly often and most pronounced in patients suffering from cancers of the digestive tract and the lungs. They may lose up to 80 percent of body fat and skeletal muscle. Muscle loss leads to weakness and immobility of patients and poorer response to treatment. An estimated 20 percent of cancer deaths are considered to be a direct consequence of cachexia, with failure of the respiratory muscles as a frequent cause of death.
"Doctors used to believe that cancer re-programs metabolism in such a way that all energy goes into tumor growth," says Prof. Dr. Stephan Herzig, who heads a joint research department of the German Cancer Research Center (DKFZ), Heidelberg University and Heidelberg University Hospital. However, by now researchers presume that cachexia is the body's response to various harmful stimuli originating directly from the growing tumor. In his endeavor to find the causes of cachexia, Stephan Herzig, an expert in metabolism, took a closer look at the liver as the control center of metabolism for the first time. "Cachexia patients frequently have an inflamed fatty liver this was a major clue for this organ being involved."
The researchers discovered that cancerous mice have extremely low lipid (blood fat) levels meaning that their bodies lack the most important energy source. However, they accumulate fat in the liver. The low lipid levels in the diseased animals are due to their liver releasing only very little VLDL (very low density lipoprotein). This lipoprotein is the vehicle that transports fats in the blood. Moreover, the genes for all major steps of lipogenesis are blocked in the livers of cancerous mice.
"This is a clear indication of a central gene switch in the liver driving cachexia", say
|Contact: Dr. Sibylle Kohlstdt|
Helmholtz Association of German Research Centres