Preclinical Study Reveals How Alcohol Promotes Fat Buildup in Liver

Cedars-Sinai investigators have discovered a signaling interaction between two proteins in cells that controls fat accumulation in the livers of laboratory mice with alcohol-associated liver disease. The findings point to a potential method to reduce liver damage in patients with the condition.

Excessive fat in the liver is an early characteristic of alcohol-associated liver disease, which is the most frequent underlying cause of alcohol-associated deaths, according to the U.S. Centers for Disease Control and Prevention. The new study found that a specific cellular signaling pathway, which helps maintain normal fat levels in the liver, was suppressed in alcohol-associated liver disease mice. The findings were published in the peer-reviewed journal Signal Transduction and Targeted Therapy.

“Therapeutic approaches that control fat accumulation may be able to stop liver disease from progressing to a more advanced state,” said Komal Ramani, PhD, associate professor of Medicine and Biomedical Sciences, member of the Karsh Division of Gastroenterology and Hepatology in the Department of Medicine at Cedars-Sinai and corresponding author of the study. “Based on our research, one possible treatment could involve creating a drug to mimic the interaction that is integral to the signaling pathway, to normalize fat levels in the liver.”

Other Cedars-Sinai authors include Chandana Thimme Gowda, Mallikarjuna Siraganahalli Eshwaraiah, Jiaohong Wang, Youngyi Lim, and co-corresponding authors Maria Lauda Tomasi and Nirmala Mavila.

Funding: This work was supported by NIH grant R01AA029988 (PI: Komal Ramani, Co-I’s-Nirmala Mavila, and Maria Lauda Tomasi).

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