Nutriproteomics and Nutrigenomics: Exploring the Mechanism Behind omega-3 Polyunsaturated Fatty Acids, Homocysteine and Glucose Metabolism

Tao      Huang; Ju-Sheng      Zheng; Nestor      Mojica; Duo      Li

Abstract

Hyperhomocysteinemia (HHcy): A condition that epidemiological studies have shown to be associated with increased risk of vascular disease and type 2 diabetes (T2D), arises from disrupted homocysteine (Hcy) and glucose metabolism. Our previous studies evaluating the regulation of Hcy metabolism from the molecular, cell, animal and population levels have demonstrated that utilization of Hcy by the trans-sulfuration and remethylation pathways is regulated by omega-3 polyunsaturated fatty acids (PUFA). This interaction was then identified as having protective effects on the cardiovascular system. Furthermore, observational studies we conducted found potential beneficial effects of omega-3 PUFA on insulin sensitivity and T2D.

To date, no literature reports have discussed the mechanism behind metabolism of omega-3 PUFA, Hcy and glucose from a nutriproteomic and nutrigenomic point of view. This review comprehensively summarizes the metabolism of omega-3 PUFA, Hcy and glucose; and their regulation by omega-3 PUFA on critical gene expression, a key enzyme activity involved in the Hcy metabolic and insulin signaling pathways.

In summary, high dietary omega-3 PUFA decreases blood Hcy and glucose concentrations. Omega-3 PUFA decreases the concentration of Hcy despite increasing MAT activity and up-regulating MAT mRNA expression through compensatory cystathionine-g-lyase mRNA expression, both of which are involved in Hcy metabolism. Omega-3 PUFA had a beneficial effect on insulin sensitivity and directly targeted insulin signaling pathway via increasing insulin receptor number, tyrosine phosphrylation of IRS-1, serine phosphorylation of Akt, gene expression of IRS-1, IRS-2 and GLUT-4 in different tissues. More research is warranted to explore the precise mechanism.

Keywords: Glucose, Hcy, nutrigenomics, nutriproteomics, ometa-3 PUFA.

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