title: Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.|Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Murali
authors: M
authors: Ganesan
authors: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Dan
authors: D
authors: Feng
authors: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Ryan W
authors: RW
authors: Barton
authors: Department of Internal Medicine, Carolinas Medical Center, Charlotte, North Carolina.
authors: Paul G
authors: PG
authors: Thomes
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.|Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Benita L
authors: BL
authors: McVicker
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.|Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Dean J
authors: DJ
authors: Tuma
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.|Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
authors: Natalia A
authors: NA
authors: Osna
authors: Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska. kkharbanda@unmc.edu.|Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska. kkharbanda@unmc.edu.|Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska. kkharbanda@unmc.edu.
authors: Kusum K
authors: KK
authors: Kharbanda
mesh_terms: D000579:Amidinotransferases / Q000378:metabolism; D000818:Animals; D003401:Creatine / Q000627:therapeutic use*; D019587:Dietary Supplements; D005235:Fatty Liver, Alcoholic / Q000517:prevention & control*; D050937:Guanidinoacetate N-Methyltransferase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D050937:Guanidinoacetate N-Methyltransferase; D000579:Amidinotransferases; C020681:glycine amidinotransferase; D003401:Creatine
keywords: Alcohol; Creatine; Hepatic Steatosis; S-Adenosylhomocysteine:S-Adenosylmethionine