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October 17, 2008

Resveratrol prevents alcoholic fatty liver disease in mouse model

Resveratrol prevents alcoholic fatty liver disease in mouse model

The October, 2008 issue of the American Journal of Physiology-Gastrointestinal and Liver Physiology reported the finding of researchers at the University of South Florida Health Sciences Center in Tampa of a protective effect for resveratrol against alcoholic fatty liver disease in mice. Resveratrol, a polyphenol found in grapes, red wine, peanuts and berries, has been associated with a growing number of benefits in laboratory studies, including anti-inflammatory, anticancer and positive cardiovascular effects.

Chronic alcohol consumption can cause fat to accumulate in the liver, and can lead to cirrhosis, fibrosis, and liver failure. Laboratory research has associated alcoholic fatty liver with the inhibition of two signaling molecules, sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), which regulate the liver’s fat metabolism pathways. Inactivation of these molecules allows fat to accumulate in the liver. Acting on the finding of previous experiments that identified resveratrol as an activator of SIRT1 and AMPK, Min You and colleagues fed mice low fat diets supplemented with or without ethanol (alcohol) and/or a low or high dose of resveratrol, and measured the expression of SIRT1 and AMPK in the animals’ livers. They confirmed that resveratrol activated SIRT1 and AMPK in the mice that received alcohol, which prevented fatty liver. Increased expression of the molecules was associated with a reduction of sterol regulatory element binding protein, activation of peroxisome proliferator-activated receptor gamma co-activator alpha, elevation of circulating adiponectin, which helps control obesity, and enhanced expression of the liver’s adiponectin receptors. Interestingly, alcohol appeared to enhance resveratrol’s positive effects, noted Dr You, who is a member of the Department of Molecular Pharmacology & Physiology at the University of South Florida College of Medicine’s School of Basic Biomedical Sciences.

“Resveratrol treatment led to reduced lipid synthesis and increased rates of fatty acid oxidation and prevented alcoholic liver steatosis,” the authors concluded. “Our study suggests that resveratrol may serve as a promising agent for preventing or treating human alcoholic fatty liver disease.”

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Health Concern Life Extension Highlight

Cirrhosis and liver disease

The many possible liver diseases can be grouped loosely into three categories: hepatocellular diseases, cholestatic diseases, and mixed forms. In hepatocellular diseases, the liver is typically inflamed and shows signs of injury. Over time, liver cells may begin to die. Causes of hepatocellular liver disease include alcoholic cirrhosis and viral hepatitis, both of which attack liver cells directly. In cholestatic diseases, the flow of fluid through the liver is blocked by such things as gall stones, liver cancer, or biliary cirrhosis. In mixed forms of liver disease, both conditions are present.

The pattern and onset of symptoms can help physicians determine what kind of liver disease is present. Symptoms of liver disease include jaundice, fatigue, itching, pain in the upper abdomen, distention of the abdomen, and intestinal bleeding. However, many forms of liver disease have no symptoms and are diagnosed only during routine blood tests that detect abnormalities in the markers of liver function.

The most common cause of fatty liver disease is alcohol consumption, but it can also be caused by a number of other conditions, including obesity, diabetes, and elevated triglyceride levels. If the condition is associated with obesity, it is sometimes called nonalcoholic fatty liver disease, or NAFLD. Up to one-third of patients with NAFLD also have type 2 diabetes, high cholesterol levels, or both. NAFLD is closely associated with metabolic syndrome, which is a related cluster of conditions, including obesity, diabetes, elevated triglycerides, and high blood pressure, that is considered a major risk factor for heart attack. Fatty liver disease is exacerbated by inflammation within the liver, which may hasten its progression to cirrhosis.

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