Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis. (1st September 2016)

• Record Type: Journal Article
• Authors: Ganesan, Murali; Feng, Dan; Barton, Ryan W.; Thomes, Paul G.; McVicker, Benita L.; Tuma, Dean J.; Osna, Natalia A.; Kharbanda, Kusum K.
• Is Part Of: Alcoholism. Volume 40:Number 11(2016)
• Page Start: 2312
• Page End: 2319
• Publication Date: 2016-09-01
• Subjects: Hepatic Steatosis -- S‐Adenosylhomocysteine:S‐Adenosylmethionine -- Alcohol -- Creatine; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13214
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Background: Alcohol‐induced reduction in the hepatocellular S ‐adenosylmethionine (SAM): S ‐adenosylhomocysteine (SAH) ratio impairs the activities of many SAM‐dependent methyltransferases. These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (GAMT) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as GAMT‐mediated reactions consume as much as 40% of all the SAM‐derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare SAM, preserve the hepatocellular SAM:SAH ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions. Methods: For these studies, male Wistar rats were pair‐fed the Lieber‐DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5 weeks of feeding, relevant biochemical and histological analyses were performed. Results: We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol‐induced impairments in proteasome activity. The lower hepatocellular SAM:SAH ratio seen in the EtOH‐fed rats was also not normalized or SAM levels spared when these rats were fed the creatine‐supplemented EtOH diet. However, a >10‐fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine‐supplemented diets. Conclusions: Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high‐fat‐diet‐induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular SAM:SAH, still remains our best option for treating alcoholic steatosis. Abstract : Dietary creatine supplementation did not prevent alcoholic steatosis despite its known efficacy in preventing high‐fat diet‐induced fat accumulation in the liver. The lower hepatocellular SAM: SAH ratio seen in the ethanol‐fed rats was also not normalized or SAM levels spared when these rats were fed the creatine‐supplemented ethanol diet. Betaine, a pro‐methylating agent that maintains the hepatocellular SAM: SAH ratio still remains our best option for treating alcoholic steatosis.