The cannabinoid receptors best known for delivering the psychological effects of marijuana also explain the connection between chronic alcohol use and a buildup of fat in the liver, according to a report in the March issue of Cell Metabolism, a publication of Cell Press.
Alcoholic fatty liver can progress to more serious disease, and alcoholism is a leading cause of liver disease in Western societies.
The researchers also found that mice treated with rimonabant, a drug designed to block cannabinoid receptors, become resistant to alcohol's fat-building effects in the liver. Rimonabant is now in use for weight loss in several European countries but has not received FDA approval for use in the United States.
“What makes these findings particularly interesting from our perspective is that they may have practical implications,” said George Kunos of the National Institute on Alcohol Abuse and Alcoholism. “Treatment of animals with a [cannabinoid receptor] antagonist largely prevented alcohol's effect. It suggests that the development of fatty liver in those who use alcohol could be interfered with, or perhaps reversed, with such treatment.”
In addition to alcoholism, obesity can also lead to the development of fatty liver disease. Scientists have shown that natural cannabinoids, so-called endocannabinoids, and CB1 cannabinoid receptors in the livers of mice are increased when animals are fed a high-fat diet. Studies have also shown that mice lacking CB1 receptors and mice treated with drugs that block these receptors are protected from obesity and fatty liver.
“Similar to high-fat diet, chronic ethanol exposure can increase endocannabinoid levels, at least in the brain,” the researchers said. The apparent similarities between diet- and ethanol-induced changes in fat metabolism and endocannabinoid activity in the liver suggested that endocannabinoids might also be a culprit in ethanol-induced fatty liver.