Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism

Abstract

The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.

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Abbreviations

BHMT:

Betaine-homocysteine S-methyltransferase

CβS:

Cystathionine-β-synthase

CDD:

Choline deficient diet

ChDh:

Choline dehydrogenase

CDO:

Cysteine dioxygenase

Chka:

Choline kinase alpha

Chkb:

Choline kinase beta

Cta:

Choline-phosphate cytidylyltransferase A

Cth:

Cystathionase

CTP:

Phosphorylcholine cytidylyltransferase

ET:

Ethanolamine phosphate cytidylyltransferase 2

Gclc:

Glutamyl-cysteine synthetase

Gnmt:

Glycine N-methyltransferase

Hcy:

Homocysteine

HHcy:

Hyperhomocysteinemia

Mat1:

Methionine adenosyltransferase

Mgat1:

Monoacylglycerol O-acyltransferase 1

MS:

Methionine synthase

Mthfr:

5,10-Methylenetetrahydrofolate reductase

PE:

Phosphatidylethanolamine

PEMT:

Phosphatidylehanolamine N-methyltranferase

PC:

Phosphatidylcholine

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

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Acknowledgments

The authors acknowledge Ms. Kathy Clow for skilled technical assistance. Supported by Grants from the Canadian Institutes for Health Research (JTB/MEB), Natural Sciences and Engineering Research Council of Canada (RLJ grant number 386652) and Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil Protocol 07/08099-5 (RD). K.K. was supported by an Alexander Graham Bell Canada graduate scholarship from the Natural Sciences and Engineering Research Council of Canada. R.L.J. holds a Canadian Institutes of Health Research New Investigator Award.

Conflict of interest

None of the authors has either financial or personal conflicts of interest to declare.

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Correspondence to Rafael Deminice.

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Deminice, R., da Silva, R.P., Lamarre, S.G. et al. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism. Amino Acids 47, 839–846 (2015). https://doi.org/10.1007/s00726-014-1913-x

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Keywords

  • Betaine
  • Liver
  • High-fat diet
  • S-adenosylmethionine