Featured Research

from universities, journals, and other organizations

Liver controls wasting in cancer

Date:
January 14, 2013
Source:
Helmholtz Association
Summary:
Many cancer patients suffer from a dramatic loss of fat and muscle mass. This extreme wasting, or cachexia, is often the actual cause of death in cancer patients. Scientists have now discovered in mice that tumors stimulate the production of a key gene switch in the liver. Activity of this switch lowers blood fat levels so that the animals lose weight. This finding may lead to approaches to slow down this fatal loss of body mass.

Many cancer patients suffer from a dramatic loss of fat and muscle tissue. This extreme wasting, or cachexia, is often the actual cause of death in cancer patients. Heidelberg scientists have now discovered in mice that tumors stimulate the production of a key gene switch in the liver. Activity of this switch lowers blood fat levels so that the animals lose weight. The researchers have been the first to demonstrate that the liver controls cancer-induced cachexia. This finding may lead to approaches to slow down this fatal loss of body mass.

Related Articles


Cachexia or wasting affects up to 70 percent of all cancer patients depending on the type of cancer. It is characterized by a dramatic loss of body weight 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 focusing all energy 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. To explore the causes of cachexia, Stephan Herzig, an expert in metabolism, took a closer look at the liver as the key controlling point of metabolism. "Cachexia patients frequently show an inflamed fatty liver -- this was a major clue for this organ being involved."

The researchers found extremely low lipid (blood fat) levels in cancerous mice, therefore they 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). VLDL facilitates the transport of fat in the bloodstream. 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," says Stephan Herzig. He therefore searched for differences in protein switches regulating gene activity and hence hepatic energy metabolism in cancerous and healthy mice. Herzig's team found significant differences in a poorly studied gene switch called TSC22D4, which is found in larger amounts in cancerous mice than in healthy control mice.

Herzig's team was able to clearly demonstrate the key role of TSC22D4 in the onset of cachexia. When the researchers silenced the switch specifically in the animals' livers the organ subsequently went back to producing enough VLDL to make lipid levels in the cancerous animals rise. In addition, the genes involved in lipogenesis got boosted again.

"Our results prove, for the first time, that dramatic loss of body mass may be controlled by the liver," says Stephan Herzig. "We also learned recently that TSC22D4 shows exactly the same effect in human hepatic cells. There is evidence that certain metabolites control this gene switch and might offer the possibility to slow down the fatal wasting process. However, we don´t have proven this approach by now. This is what we will do next."


Story Source:

The above story is based on materials provided by Helmholtz Association. Note: Materials may be edited for content and length.


Journal Reference:

  1. Allan Jones, Kilian Friedrich, Maria Rohm, Michaela Schäfer, Carolyn Algire, Philipp Kulozik, Oksana Seibert, Karin Müller-Decker, Tjeerd Sijmonsma, Daniela Strzoda, Carsten Sticht, Norbert Gretz, Geesje M. Dallinga-Thie, Barbara Leuchs, Manfred Kögl, Wolfgang Stremmel, Mauricio Berriel Diaz and Stephan Herzig. Transforming growth factor-beta1 Stimulated Clone-22 D4 is a molecular output of hepatic wasting metabolism. EMBO Molecular Medicine, 2012

Cite This Page:

Helmholtz Association. "Liver controls wasting in cancer." ScienceDaily. ScienceDaily, 14 January 2013. <www.sciencedaily.com/releases/2013/01/130114101734.htm>.
Helmholtz Association. (2013, January 14). Liver controls wasting in cancer. ScienceDaily. Retrieved December 17, 2014 from www.sciencedaily.com/releases/2013/01/130114101734.htm
Helmholtz Association. "Liver controls wasting in cancer." ScienceDaily. www.sciencedaily.com/releases/2013/01/130114101734.htm (accessed December 17, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, December 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) — A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) Video provided by AP
Powered by NewsLook.com
Yoga Could Be As Beneficial For The Heart As Walking, Biking

Yoga Could Be As Beneficial For The Heart As Walking, Biking

Newsy (Dec. 17, 2014) — Yoga can help your weight, blood pressure, cholesterol and heart just as much as biking and walking does, a new study suggests. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins