(16-06-12) Nutrigenomics and Nutrigenetics of ?3 Polyunsaturated Fatty Acids.

Vanden Heuvel JP.
Abstract
Diets rich in ?3 polyunsaturated fatty acids (?3-PUFAs) such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated with decreased incidence and severity of several chronic diseases including cardiovascular disease (CVD) and cancer. At least some of the beneficial effects of these dietary fatty acids are via metabolites such as prostaglandins, leukotrienes, thromboxanes, and resolvins. The effects of ?3-PUFAs are in contrast to those of fatty acids with virtually identical structures, such as the ?6-PUFAs linoleic acid and arachidonic acid, and their corresponding metabolites. The purpose of this chapter is to discuss both the nutrigenomics (nutrient-gene interactions) and nutrigenetics (genetic variation in nutrition) of dietary fatty acids with a focus on the ?3-PUFAs (Gebauer et al., 2007(1)). Important in the biological response for these fatty acids or their metabolites are cognate receptors that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with CVD and cancer. Four nuclear receptor (NR) subfamilies will be emphasized as receptors that respond to dietary and endogenous ligands: (1) peroxisome proliferator-activated receptors, (2) retinoid X receptors, (3) liver X receptors, and (4) farnesoid X receptor. In addition to the different responses elicited by varying structures of fatty acids, responses may vary because of genetic variation in enzymes that metabolize ?3- and ?6 fatty acids or that respond to them. In particular, polymorphisms in the fatty acid desaturases and the aforementioned NRs contribute to the complexity of nutritional effects seen with ?3-PUFAs. Following a brief introduction to the health benefits of ?3-PUFAs, the regulation of gene expression by these dietary fatty acids via NRs will be characterized. Subsequently, the effects of single-nucleotide polymorphisms (SNPs) in key enzymes involved in the metabolism and response to ?3-PUFAs will be described. An outline of the events to be explored is shown in Fig. 1. Understanding the nutrigenomics and nutrigenetics of dietary fatty acids is key to understanding the etiology, as well as prevention, of critically important human diseases including CVD and cancer.

Source: Prog Mol Biol Transl Sci. 2012;108:75-112.

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