Polyunsaturated fatty acid regulation of gene transcription: A molecular mechanism to improve the metabolic syndrome

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA ), particularly those of the (n-3) family, play pivotal roles as "fuel part itioners" in that they direct fatty acids away from triglyceride storage an d toward oxidation, and that they enhance glucose flux to glycogen. In doin g this, PUFA may protect against the adverse symptoms of the metabolic synd rome and reduce the risk of heart disease. PUFA exert their beneficial effe cts by up-regulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously downregulating genes encoding pro teins of lipid synthesis. PUFA govern oxidative gene expression by activati ng the transcription factor peroxisome proliferator-activated receptor a. P UFA suppress lipogenic gene expression by reducing the nuclear abundance an d DNA-binding affinity of transcription factors responsible for imparting i nsulin and carbohydrate control to lipogenic and glycolytic genes. In parti cular, PUFA suppress the nuclear abundance and expression of sterol regulat ory element binding protein-1 and reduce the DNA-binding activities of nucl ear factor Y, Spl and possibly hepatic nuclear factor-4, Collectively, the studies discussed suggest that the fuel "repartitioning" and gene expressio n actions of PUFA should be considered among criteria used in defining the dietary needs of (n-6) and (n-3) and in establishing the dietary ratio of ( n-6) to (n-3) needed for optimum health benefit.