title: Creatine supplementation prevents fatty liver in rats fed choline-deficient diet: a burden of one-carbon and fatty acid metabolism.
abstract: OBJECTIVE
  To examine the effects of creatine (Cr) supplementation on liver fat accumulation in rats fed a choline-deficient diet.
  
  
  METHODS
  Twenty-four rats were divided into 3 groups of 8 based on 4 weeks of feeding an AIN-93 control diet (C), a choline-deficient diet (CDD) or a CDD supplemented with 2% Cr. The CDD diet was AIN-93 without choline.
  
  
  RESULTS
  The CDD significantly increased plasma homocysteine and TNFα concentration, as well as ALT activity. In liver, the CDD enhanced concentrations of total fat (55%), cholesterol (25%), triglycerides (87%), MDA (30%), TNFα (241%) and decreased SAM concentrations (25%) and the SAM/SAH ratio (33%). Cr supplementation prevented all these metabolic changes, except for hepatic SAM and the SAM/SAH ratio. However, no changes in PEMT gene expression or liver phosphatidylcholine levels were observed among the three experimental groups, and there were no changes in hepatic triglyceride transfer protein (MTP) mRNA level. On the contrary, Cr supplementation normalized expression of the transcription factors PPARα and PPARγ that were altered by the CDD. Further, the downstream targets and fatty acids metabolism genes, UCP2, LCAD and CPT1a, were also normalized in the Cr group as compared to CDD-fed rats.
  
  
  CONCLUSIONS
  Cr supplementation prevented fat liver accumulation and hepatic injures in rats fed with a CDD for 4 weeks. Our results demonstrated that one-carbon metabolism may have a small role in mitigating hepatic fat accumulation by Cr supplementation. The modulation of key genes related to fatty acid oxidation pathway suggests a new mechanism by which Cr prevents liver fat accumulation.
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil; 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. Electronic address: deminice@ig.com.br.
authors: Rafael
authors: R
authors: Deminice
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Gabriela Salim Ferreira
authors: GS
authors: de Castro
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Lucas Vieira
authors: LV
authors: Francisco
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Lilian Eslaine Costa Mendes
authors: LE
authors: da Silva
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: João Felipe Rito
authors: JF
authors: Cardoso
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Fernando Tadeu Trevisan
authors: FT
authors: Frajacomo
authors: Department of Biochesmtry and Imunology, Faculty of Medicine of Ribeirão Preto Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Bruno Gonzaga
authors: BG
authors: Teodoro
authors: School of Physical Education of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil; Department of Biochesmtry and Imunology, Faculty of Medicine of Ribeirão Preto Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Leonardo
authors: L
authors: Dos Reis Silveira
authors: Nutrition and Metabolism, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, Brazil.
authors: Alceu Afonso
authors: AA
authors: Jordao
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency; D003401:Creatine / Q000008:administration & dosage*; D004032:Diet; D019587:Dietary Supplements; D005234:Fatty Liver / Q000517:prevention & control*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D014280:Triglycerides; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D008315:Malondialdehyde; D002244:Carbon; D012436:S-Adenosylmethionine; D002784:Cholesterol; D002334:Carnitine O-Palmitoyltransferase; D003401:Creatine; D002794:Choline
keywords: Choline-deficient diet; Creatine supplementation; Fat oxidation; Fatty liver; One-carbon metabolism