Thursday, March 6, 2008

Weight-Loss Drug Fights Alcoholic Fatty Liver Disease

(HealthDay News) -- Mice given the weight-loss drug rimonabant became resistant to alcohol's fat-building effects in the liver, which suggests the medication may help fight alcoholic fatty liver in humans, says a U.S. study.

Alcoholism is the leading cause of liver disease in Western societies, according to background information in the study.

Rimonabant, which blocks cannabinoid receptors, is approved for weight loss in several European countries but has not been approved in the United States. Last June, a U.S. Food and Drug Administration panel recommended that rimonabant should not be given the FDA's blessing because of continuing concerns about increased risks for suicidal thoughts among some users.

In this latest study, the researchers found that mice fed a low-fat diet and ethanol showed an increase in the gene encoding the CB1 cannabinoid receptor and in liver levels of an endocannabinoid called 2-arachidonoylglycerol (2-AG). These mice developed fatty livers.

Another group of mice that received the same diet plus rimonabant did not differ from mice fed a control diet. And mice lacking CB1 receptors, either throughout the body or only in the liver, were protected from alcoholic fatty liver.

"What makes these findings particularly interesting from our perspective is that they may have practical implications," said study author George Kunos, of the U.S. 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."

The findings were published in the March issue of Cell Metabolism.

"Although alcoholic fatty liver is reversible in the early stages by cessation of drinking, this is often not feasible," the study authors wrote. "The present findings suggest that treatment with a CB1 antagonist may slow the development of fatty liver and thus prevent its progression to more severe and irreversible forms of liver disease."

Drugs that selectively act on CB1 receptors found outside of the brain might help fight fatty liver with less risk of side effects such as anxiety and depression, they said.

"Rimonabant has recently been introduced in Europe for the treatment of visceral obesity and the metabolic syndrome, which themselves are known risk factors for [liver disease]. Clinical trials testing the effectiveness of CB1 receptor blockers in the treatment of both alcoholic and nonalcoholic fatty liver and their more severe sequelae may be warranted," the researchers concluded.

More information
The American Liver Foundation has more about fatty liver.

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