Chronic alcohol drinking affects 16 million people in the United States, and one of the results is fatty liver damage leading to cirrhosis (scarring). Liver cirrhosis is the 12th-leading cause of death nationwide.
Researchers at UT Health San Antonio’s Sam & Ann Barshop Institute for Longevity & Aging Studies and 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.
Normal liver (mouse)
Alcoholic fatty liver
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 at UT Health San Antonio. Dr. Zang, the Ewing Halsell Distinguished Chair at the university, is the senior author of alcohol liver disease research published this year 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 UT Health San Antonio 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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