Written by Greg Arnold, DC, CSCS.  In this study of 48 mice, those who were fed only alcohol had a significant 50% decrease in liver protein function compared to control; however, those mice who were fed both alcohol and resveratrol had a 300% increase in liver protein function and those fed strictly resveratrol had a 250% increase in liver protein function. 

Alcoholic Fatty Liver Disease is estimated to affect nearly half of all heavy drinkers and nearly 95% of obese heavy drinkers (1). Heavy drinking is classified as more than two drinks per day in men and more than one drink per day in women (2)). Alcoholic Fatty Liver Disease is estimated to cost $184 billion per year (3), and as many as 10 % of men and 3 % of women may suffer from persistent problems related to the use of alcohol (4).

Research into alcohol’s role in precipitating Alcoholic Fatty Liver Disease has found that alcohol increases fat accumulation in the liver by impairing the function of certain proteins in the liver such as SIRT1 (5) and AMPK (6). Now a new study (7) has found that resveratrol, a plant antioxidant found in grapes, red wines, berries, and peanuts (8) and may benefit liver health and Alcoholic Fatty Liver Disease.

Previous research suggests that resveratrol may affect SIRT1 activity (9) and help with liver health in animals (10). Building on these findings, researchers divided mice into six groups (4 to 8 mice per group) and gave them the following each day for four weeks:

  • Group 1: Low-fat diet alone with 10% of calories as fat (6% cocoa butter and 4% safflower oil)
  • Group 2: Low-fat diet plus 200 mg per kg of bodyweight
  • Group 3: Low-fat diet plus 400 mg per kg bodyweight
  • Group 4: Low-fat diet plus ethanol (identical to the control diet but ethanol was added to account for 29% of total calories)
  • Group 5: Low-fat diet plus ethanol and 200 mg per kg of bodyweight per day resveratrol
  • Group 6: Low-fat diet plus ethanol and 400 mg per kg of bodyweight per day resveratrol

In groups 5 and 6, resveratrol was added two weeks before the end of the study. The doses used in this study have been used in previous research (11)

The researchers found that SIRT1 levels in the mice given ethanol decreased by 50% compared to the control group, but increased 250% in the resveratrol group and 300% in the resveratrol group fed ethanol. Alcohol reduced AMPK levels by 60% yet the levels were maintained in the resveratrol group. What’s more, resveratrol also increased activity of a protein called ACC, which is an indicator of AMPK activity.

Finally, the researchers looked at a liver protein called SREBP-1. Activity of this protein increases when SRT1 and AMPK are decreased. SREBP-1 activity in the alcohol groups “significantly increased” in the ethanol group compared with control group. While resveratrol “dramatically reduced” SREBP-1 protein levels in the alcohol mice, the levels were “only slightly reduced” in the resveratrol-only group.

A “surprising finding” of the study was that resveratrol increased levels of adiponectin, a protein known to play “a vital” role in Alcoholic Fatty Liver Disease (12).  Specifically, adiponectin levels were increased by 200%. For the researchers, “the present study suggests that resveratrol…may serve as [new] and promising nutritional or pharmacological [therapy] in treating human alcoholic fatty liver disease.”

Source: Ajmo, Joanne M., Xiaomei Liang, Christopher Q. Rogers, Brandi Pennock, and Min You. “Resveratrol alleviates alcoholic fatty liver in mice.” American Journal of Physiology-Gastrointestinal and Liver Physiology 295, no. 4 (2008): G833-G842.

© 2008 the American Physiological Society

Posted December 11, 2008.

References:

  1. “Alcoholic Fatty Liver” posted on The Medscape website.
  2. “Frequently Asked Questions: Alcohol” posted on the Centers for Disease Control and Prevention website.
  3. Barve A.  Treatment of alcoholic liver disease. Annals of Hepatology 2008; 7(1): January-March: 5-15.
  4. “Alcoholic Liver Disease” posted on The Columbia University website.
  5. Lieber CS, Leo MA, Wang X, Decarli LM. Effect of chronic alcohol consumption on hepatic SIRT1 and PGC-1alpha in rats. Biochem Biophys Res Commun 370: 44–48, 2008.
  6. Tomita K, Tamiya G, Ando S, Kitamura N, Koizumi H, Kato S, Horie Y, Kaneko T, Azuma T, Nagata H, Ishii H, Hibi T. AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats. Alcohol Clin Exp Res 29: 240S–240S, 2005.
  7. Ajmo et al. Resveratrol alleviates alcoholic fatty liver in mice.  Am J Physiol Gastrointest Liver Physiol. 2008; 295: G833-G842.
  8. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5: 493–506, 2006.
  9. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 280: 17187–17195, 2005.
  10. Kasdallah-Grissa A, Mornagui B, Aouani E, Hammami M, Gharbi N, Kamoun A, El-Fazaa S. Protective effect of resveratrol on ethanol-induced lipid peroxidation in rats. Alcohol Alcohol 41: 236–239, 2006.
  11. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127: 1109–1122, 200.
  12. You M, Considine RV, Leone TC, Kelly DP, Crabb DW. Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 42: 568–577, 2005.