Docosahexaenoic acid decreases plasma homocysteine via regulating enzyme activity and mRNA expression involved in methionine metabolism

Abstract 

Objective

The objective of this study was to investigate the regulatory effect of fish oil rich in ω-3 polyunsaturated fatty acids (PUFAs) on critical enzyme activity and mRNA expression involved in homocysteine (Hcy) metabolism.

Methods

Thirty-six male Sprague-Dawley rats aged 3 wk, weighing 120 ± 10 g, were randomly divided into three groups: the olive oil (OO) group, the tuna oil (TO) group, and the salmon oil (SO) group. The oil was orally administered every day using a stomach tube. Eight weeks later, plasma Hcy, phospholipids, ω-3 PUFAs, enzyme activity, and mRNA expression in tissues were determined.

Results

Compared with the control group, phospholipids, total ω-3 PUFAs, and ω-3/ω-6 PUFAs in the liver and lung were significantly elevated in the TO and SO groups; 22:6ω-3 in the liver and lung was significantly increased in the TO group; and 20:5ω-3 in the two tissues was significantly elevated in the SO group. The level of plasma Hcy was significantly decreased with TO; methionine adenosyl transferase (MAT) activity was significantly increased and MAT mRNA expression was significantly upregulated with TO; cystathionine-γ-lyase mRNA expression in TO was significantly upregulated; however, cystathionine β-synthase and S-adenosylhomocysteine hydrolases were not significantly changed when compared with control.

Conclusion

TO rich in 22:6ω-3 decreases the concentration of Hcy despite increasing MAT activity and upregulating MAT mRNA expression through compensatory cystathionine-γ-lyase mRNA expression, both of which are involved in Hcy metabolism.

Keywords: Fish oil, Gene expression, Methionine adenosyltransferase, Cystathionine β-synthase, Cystathionine-γ-lyase, S-adenosylhomocysteine hydrolase, Hydrogen sulfide