Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver

ABSTRACT

Some important environmental factors that influence the development of cardiovascular diseases (CVD) include tobacco, excess alcohol, and unhealthy diet. Methionine obtained from the diet participates in the synthesis of DNA, proteins, lipids and affects homocysteine levels, which is associated with the elevated risk for CVD development. Therefore, the aim of this study was to investigate the manner in which dietary methionine might affect cellular mechanisms underlying CVD occurrence. Swiss albino mice were fed either control (0.3% DL-methionine), methionine-supplemented (2% DL-methionine), or a methionine-deprived diet (0% DL-methionine) over a 10-week period. The parameters measured included plasma homocysteine concentrations, oxidative stress by reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, levels of inflammatory cytokines IL-1ß, TNF-α, and IL-6, as well as expression of genes associated with CVD. The levels of apolipoprotein A5 (APOA5), a regulator of plasma triglycerides, were measured. The methionine-supplemented diet increased oxidative stress by lowering the GSH/GSSG ratio in heart tissues and decreased expression of the genes Apob, Ctgf, Serpinb2, Spp1, Il1b, and Sell, but elevated expression of Thbs4, Tgfb2, Ccr1, and Vegfa. Methionine-deprived diet reduced expression of Col3a1, Cdh5, Fabp3, Bax, and Hbegf and increased expression of Sell, Ccl5, Itga2, Birc3, Msr1, Bcl2a1a, Il1r2, and Selp. Methionine-deprived diet exerted pro-inflammatory consequences as evidenced by elevated levels of cytokines IL-1ß, TNF-α, and IL-6 noted in liver. Methionine-supplemented diet increased hepatic IL-6 and cardiac TNF-α. Both methionine supplementation and deprivation lowered hepatic levels of APOA5. In conclusion, data demonstrated that a methionine-supplemented diet modulated important biological processes associated with high risk of CVD development.

Acknowledgments

The authors thank Regislaine Valéria Burim, Joana D’Arc Castania Darin, Sônia A. C. Dreossi and Dr. Regina Helena Costa Queiroz for the assistance. Lusânia MG Antunes and Rui Curi also thank CNPq for the research productivity grant.

Funding

Alexandre Ferro Aissa was sponsored with a fellowship from FAPESP. This study was sponsored by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), Brazilian Innovation Agency (FINEP; Grant #01.09.0447.00), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPESP, Grant #2010/01410-0 and #2013/02365-6, São Paulo Research Foundation (FAPESP).

Conflict of interest

There are no financial or personal interests that might pose a conflict of interest.

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Additional information

Funding

Alexandre Ferro Aissa was sponsored with a fellowship from FAPESP. This study was sponsored by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), Brazilian Innovation Agency (FINEP; Grant #01.09.0447.00), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPESP, Grant #2010/01410-0 and #2013/02365-6, São Paulo Research Foundation (FAPESP).