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Changes Identified In Cholesterol Metabolic Pathways

A new study from the has identified molecular changes responsible for abnormal and metabolism in the livers of patients with a common condition, and these changes may explain the severity of a patient’s disease and risks to their heart health.

It is estimated that a third of Americans have a fatty liver. Nonalcoholic fatty liver disease is a very common . Nonalcoholic steatohepatitis, or NASH, the more aggressive form of nonalcoholic fatty liver disease, is associated with increased cardiac risk and liver-related mortality.

The VCU findings may provide researchers with potential new targets for treatment and also allow clinicians to further refine how they assess cardiovascular risk and develop ways to reduce it in individuals with a more aggressive form of nonalcoholic fatty liver disease called nonalcoholic steatohepatitis, or NASH.

In the study, published in Cell Metabolism, the team has shown that there is not only increased production of but a decreased expression of the receptor that takes up from the blood. This would be expected to both enhance output from the liver and reduce its removal, thereby making it more available to enter blood vessels and contribute to . The liver not only makes , but also takes up from the blood.

“This indicates that there is excessive cholesterol production in the liver when one develops fatty liver disease,” said lead investigator Arun Sanyal, M.D., professor and chair in the Division of Gastroenterology, Hepatology and Nutrition in the VCU School of Medicine.

“This may be important both to drive the disease towards cirrhosis and to increase the risks of heart disease in those with fatty liver disease,” said Sanyal.


Sanyal collaborated with VCU colleagues in the VCU Division of Gastroenterology, Hepatology and Nutrition, the Department of Surgery and the Department of Pathology.
The work was supported in part by grants from the National Institutes of Health, grant numbers: 5R01DK081410-03, K24 DK 02755 and T32 DK-007150-33.
Virginia Commonwealth University