Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis

Murali Ganesan, Dan Feng, Ryan W. Barton, Paul G Thomes, Benita L McVicker, Dean J. Tuma, Natalia A Osna, Kusum Kharbanda

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2312-2319
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume40
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Creatine
S-Adenosylmethionine
S-Adenosylhomocysteine
Nutrition
Liver
Rats
Guanidinoacetate N-Methyltransferase
Methylation
Dietary Supplements
Diet
Alcohols
Betaine
Wounds and Injuries
Methyltransferases
High Fat Diet
Proteasome Endopeptidase Complex
Wistar Rats
Ethanol
Fats
Enzymes

Keywords

  • Alcohol
  • Creatine
  • Hepatic Steatosis
  • S-Adenosylhomocysteine:S-Adenosylmethionine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis. / Ganesan, Murali; Feng, Dan; Barton, Ryan W.; Thomes, Paul G; McVicker, Benita L; Tuma, Dean J.; Osna, Natalia A; Kharbanda, Kusum.

In: Alcoholism: Clinical and Experimental Research, Vol. 40, No. 11, 01.11.2016, p. 2312-2319.

Research output: Contribution to journalArticle

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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.",
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author = "Murali Ganesan and Dan Feng and Barton, {Ryan W.} and Thomes, {Paul G} and McVicker, {Benita L} and Tuma, {Dean J.} and Osna, {Natalia A} and Kusum Kharbanda",
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AU - Feng, Dan

AU - Barton, Ryan W.

AU - Thomes, Paul G

AU - McVicker, Benita L

AU - Tuma, Dean J.

AU - Osna, Natalia A

AU - Kharbanda, Kusum

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AB - 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.

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