Naturally occurring protein could fight alcoholic liver disease

Alcoholic fatty liver (mouse) versus normal liverChronic alcohol drinking affects 16 million people in the U.S., and one of the results is fatty liver damage leading to cirrhosis, or scarring. Liver cirrhosis is the 12th-leading cause of death nationwide.

Researchers at the university’s Sam and Ann Barshop Institute for Longevity and Aging Studies and the Department of Molecular Medicine have identified a nutrient-sensing pathway that, if it can be blocked by pharmacological means, could either prevent this liver damage or be a treatment for it.

The scientists believed chronic alcohol consumption would increase activity of a nutrient sensor called mTORC1 and that this would play a role in alcoholic fatty liver, said Mengwei Zang, M.D., Ph.D., associate professor of molecular medicine. Dr. Zang, the Ewing Halsell Distinguished Chair, is the senior author of alcohol liver disease research published in the journal Hepatology.

To find out, the researchers measured liver mTORC1 levels in two groups of mice. Both groups drank a normal liquid diet for five days, with one group continuing
on the normal diet for the duration of the study. The other group received a 5 percent ethanol liquid diet for 10 days and was allowed a one-time binging of the ethanol diet on day 16.

“We found exciting results—chronic alcohol consumption increased liver mTORC1 activity in mice and in patients,” Dr. Zang said.

Dr. Zang also reported that a protein called DEPTOR inhibits mTORC1 activity. Because DEPTOR is a naturally occurring protein in our bodies, she views it as a promising target of intervention to curb the fatty liver disease process.

Rapamycin is a compound that reduces mTORC1 activity. The team, including first author Hanqing Chen, Ph.D., and second author Feng Shen, M.D., Ph.D., conducted further studies in which they compared two groups of mice that were fed an ethanol liquid diet. One group additionally received rapamycin while the other did not. The rapamycin treatment group showed inhibited mTORC1 activity and decreased liver damage, Dr. Zang said.

“Based on these interesting findings, I hope in the future that we can target DEPTOR, perhaps with a pill, and treat alcoholic fatty liver disease,” she said.

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