The liver may control the dramatic loss of body mass seen in persons with cancer, and manipulation of a specific gene switch may delay the wasting process, according to recent research results appearing in EMBO Molecular Medicine.
Up to 70% of persons with cancer have cachexia, or wasting, which is characterized by dramatic weight loss independent of food intake. The condition is especially pronounced in persons with cancers of the digestive tract and the lungs, who may lose up to 80% of their body fat and skeletal muscle. This can lead to poorer response to treatment and death.
In a statement issued by the German Cancer Research Center in Heidelberg, Germany, where study author and metabolism expert Dr. Stephan Herzig heads a joint research department, Herzig explained that cachexia is presumed to be the body’s response to various harmful stimuli originating directly from the growing tumor. However, when he and his team evaluated the liver as the control center of metabolism, they found that persons with cachexia frequently have an inflamed, fatty liver. “This was a major clue for this organ being involved,” affirmed Herzig.
Herzig and colleagues further found that cancerous mice had extremely low lipid levels and thus a lack of fat. The animals did, however, accumulate fat in the liver, but the organ released only very small amounts of very-low-density lipoprotein (VLDL) to trnasport blood fats. In addition, the genes for all major steps of lipogenesis were blocked in the livers of cancerous mice, which Herzig saw as a clear indication that a central gene switch in the liver drives cachexia.
After finding larger amounts of a gene switch called TSC22D4 in cancerous mice than in healthy control mice, the investigators silenced the switch in the animal livers. The organ subsequently went back to producing enough VLDL to raise lipid levels in the cancerous mice, and the genes involved in lipogenesis were reactivated.
“We also know by now that TSC22D4 has exactly the same effect in human hepatic cells,” noted Herzing. “There is evidence suggesting that this gene switch can be controlled via specific metabolic products and that we might thus be able to slow down the fatal wasting process.”