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Creatine supplementation as a possible new therapeutic approach for fatty liver disease: early findings

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Abstract

Over the last few years, consistent data have demonstrated that creatine (Cr) supplementation prevents the accumulation of fat in rat liver as well as the progression of fatty liver disease in different situations. Studies have demonstrated that Cr is effective and prevents fatty liver in high-fat and choline-deficient diets and in hepatoma cells in vitro. Because Cr synthesis is responsible for a considerable consumption of hepatic methyl groups, studies have tested the idea that Cr supplementation could modulate phospholipid formation and VLDL secretion. Studies have also demonstrated Cr is able to modulate the expression of key genes related to fatty acid oxidation in hepatocyte cell culture and in rat liver. However, to date, the mechanism by which Cr exerts protective effects against fatty liver is poorly understood. Therefore, the present review aims to summarize the studies involving the therapeutic use of Cr supplementation on fatty liver disease and to explore the mechanisms involved in one-carbon and fatty acid metabolism for the preventive effects of Cr supplementation on fat liver accumulation. Although a small number of studies have been conducted to date, we consider Cr as a new and promising therapeutic strategy to control fat accumulation in the liver as well as the progression of fatty liver disease.

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Abbreviations

AMPK:

AMP-activated protein kinase

BHMT:

Betaine-homocysteine S-methyltransferase

CK:

Creatine kinase

DNL:

De novo lipogenesis

McA:

McArdle

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

NEFA:

Non-esterified fatty acids

PE, PEMT:

Phosphatidylethanolamine N-methyltranferase

PL:

Phosphatidylcholine

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

TAG:

Triacylglycerols

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Acknowledgments

Deminice R is suported by Brazilian Grant from Coordenação de Aperfeiçoamento de Pessoal do Ensino Superior (Capes: 88881.068035/2014-01); de Castro GS is supported by Science without Borders Program—Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (246567/2013-9). Brosnan JT and Brosnan ME are supported by grant #97851 from the Canadian Institutes for Health Research.

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Authors and Affiliations

  1. Department of Physical Education, Faculty of Physical Education and Sport, State University of Londrina, Rodovia Celso Garcia Cid, Pr 445 km 380, Campus Universitário, Londrina, Paraná, Brazil

    Rafael Deminice

  2. Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK

    Gabriela S. de Castro

  3. Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Canada

    Margaret E. Brosnan & John T. Brosnan

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  1. Rafael Deminice
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  2. Gabriela S. de Castro
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  3. Margaret E. Brosnan
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  4. John T. Brosnan
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Correspondence to Rafael Deminice.

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Deminice, R., de Castro, G.S., Brosnan, M.E. et al. Creatine supplementation as a possible new therapeutic approach for fatty liver disease: early findings. Amino Acids 48, 1983–1991 (2016). https://doi.org/10.1007/s00726-016-2183-6

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